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CD003317

Acupuncture appeared to be safe but without clear evidence of benefit. The number of patients is too small to be certain whether acupuncture is effective for treatment of acute ischaemic or haemorrhagic stroke. Larger, methodologically-sound trials are required.

Does acupuncture have additional value to standard poststroke motor rehabilitation?

A significant number of patients remain severely disabled after stroke despite rehabilitation with standard treatment modalities. Acupuncture has been reported as an alternative modality. This study aims to examine whether acupuncture has additional value to standard poststroke motor rehabilitation. A prospective randomized controlled trial (RCT) was carried out in a stroke rehabilitation unit in Hong Kong. One hundred six Chinese patients with moderate or severe functional impairment were included at days 3 to 15 after acute stroke. They were stratified into the moderate and the severe groups before randomization into the control arm receiving standard modalities of treatment, which included physiotherapy, occupational and speech therapy, and skilled medical and nursing care, and the intervention arm receiving in addition traditional Chinese manual acupuncture. A mean of 35 acupuncture sessions on 10 main acupoints were performed over a 10-week period. Outcome measures included Fugl-Meyer assessment, Barthel Index, and Functional Independence Measure, respectively, at weeks 0, 5, and 10, performed by blinded assessors. At baseline, patients in each arm were comparable in all important prognostic characteristics. No statistically significant differences were observed between the 2 arms for any of the outcome measures at week 10 or outcome changes over time. Traditional Chinese manual acupuncture on the body has no additional value to standard poststroke motor rehabilitation.

CD003317

Acupuncture appeared to be safe but without clear evidence of benefit. The number of patients is too small to be certain whether acupuncture is effective for treatment of acute ischaemic or haemorrhagic stroke. Larger, methodologically-sound trials are required.

Acupuncture and transcutaneous nerve stimulation in stroke rehabilitation: a randomized, controlled trial.

In small trials with control groups that receive no intervention, acupuncture has been reported to improve functional outcome after stroke. We studied effects of acupuncture and transcutaneous electrical nerve stimulation on functional outcome and quality of life after stroke versus a control group that received subliminal electrostimulation. In a multicenter randomized controlled trial involving 7 university and district hospitals in Sweden, 150 patients with moderate or severe functional impairment were included. At days 5 to 10 after acute stroke, patients were randomized to 1 of 3 intervention groups: (a) acupuncture, including electroacupuncture; (b) sensory stimulation with high-intensity, low-frequency transcutaneous electrical nerve stimulation that induces muscle contractions; and (c) low-intensity (subliminal) high-frequency electrostimulation (control group). A total of 20 treatment sessions were performed over a 10-week period. Outcome variables included motor function, activities of daily living function, walking ability, social activities, and life satisfaction at 3-month and 1-year follow-up. At baseline, patients in each group were closely similar in all important prognostic variables. At 3-month and 1-year follow-ups, no clinically important or statistically significant differences were observed between groups for any of the outcome variables. The 3 treatment modalities were all conducted without major adverse effects. When compared with a control group that received subliminal electrostimulation, treatment during the subacute phase of stroke with acupuncture or transcutaneous electrical nerve stimulation with muscle contractions had no beneficial effects on functional outcome or life satisfaction.

CD006325

Since no RCTs or CCTs in which only the use of MTX differed between the treatment groups were identified, no definitive conclusions can be made about the effects on antitumour efficacy, toxicities and quality of life of the addition of MTX to treatment of children and young adults with primary high-grade osteosarcoma. The same is true for combinations of treatment including and not including MTX other than treatment with MTX versus treatment with cisplatin. Only 1 RCT comparing MTX with cisplatin treatment was available and therefore, no definitive conclusions can be made about the effectiveness of these agents in children and young adults with primary high-grade osteosarcoma. Furthermore, this study was performed in a different treatment era. Nowadays single agent treatment of osteosarcoma is considered inadequate. Based on the currently available evidence, we are not able to give recommendations for the use of MTX in clinical practice. More high quality research is needed.

Comparison of intra-arterial cis-diamminedichloroplatinum II with high-dose methotrexate and citrovorum factor rescue in the treatment of primary osteosarcoma.

A randomized two-arm study was undertaken to determine relative tumoricidal effects of intra-arterial cis-diamminedichloroplatinum II (I/A-CDP) and high-dose methotrexate with citrovorum factor rescue (MTX-CF) in the treatment of the primary tumor in patients with osteosarcoma. Responses were evaluated by clinical, radiographic, angiographic, and pathologic parameters. Fifteen patients were randomized to receive MTX-CF and 15 to I/A-CDP. In the MTX-CF arm there were four responses (three complete responses, one partial response) whereas in the I/A CDP arm there were nine responses (seven complete responses, two partial responses). Two patients who failed MTX-CF and requested alternative treatment with I/A-CDP also responded. The total I/A-CDP response was 11/17.

CD008407

More women experienced pain relief, and fewer had additional pain relief, with paracetamol compared with placebo, although potential adverse effects were not assessed and generally the quality of studies was unclear.

Acetaminophen extra strength capsules versus propoxphene compound-65 versus placebo: a double-blind study of effectiveness and safety.

CD008407

More women experienced pain relief, and fewer had additional pain relief, with paracetamol compared with placebo, although potential adverse effects were not assessed and generally the quality of studies was unclear.

Ibuprofen and acetaminophen in the relief of postpartum episiotomy pain.

A single-dose, double-blind, randomized clinical trial was conducted to examine the relative analgesic efficacy of ibuprofen 400 mg (n = 36), acetaminophen 1000 mg (n = 37), and placebo (n = 38) in postpartum patients who had moderate to severe pain after episiotomy. At regular intervals over 4 hours, patients evaluated pain severity and relief on categorical scales and completed a categorical overall evaluation at the end of the trial. Both active agents were effective compared with placebo (P less than .05). Ibuprofen 400 mg was more effective than acetaminophen 1000 mg for the sum of pain intensity difference, total pain relief, and reduction of pain by more than 50% (P less than .05), suggesting a more rapid onset of action and a more prolonged effect by ibuprofen 400 mg. No adverse effects were reported. Based on the results of this conventional postpartum episiotomy pain model, both agents are considered efficacious and ibuprofen 400 mg is a more effective analgesic for the relief of acute pain than acetaminophen 1000 mg.

CD008407

More women experienced pain relief, and fewer had additional pain relief, with paracetamol compared with placebo, although potential adverse effects were not assessed and generally the quality of studies was unclear.

Acetaminophen with codeine for the relief of severe pain in postpartum patients.

CD008407

More women experienced pain relief, and fewer had additional pain relief, with paracetamol compared with placebo, although potential adverse effects were not assessed and generally the quality of studies was unclear.

A double-blind randomized study of an aspirin/caffeine combination versus acetaminophen/aspirin combination versus acetaminophen versus placebo in patients with moderate to severe post-partum pain.

In a double-blind, randomized controlled trial among 500 post-partum patients experiencing moderate to severe pain, a single oral dose of an aspirin/caffeine combination (800 mg aspirin, 65 mg caffeine) provided significantly more pain relief at 2 hours than did a higher dose of an acetaminophen/aspirin combination (648 mg acetaminophen, 648 mg aspirin) and a higher dose of acetaminophen alone (1000 mg acetaminophen). At 3 and 4 hours, the acetaminophen/aspirin combination as well as the aspirin/caffeine combination were significantly superior to acetaminophen alone. At all times, all three drugs were significantly superior to placebo. There were no clinically significant adverse reactions. These results provide evidence of a potentiating effect of caffeine on aspirin's analgesic potency.

CD008407

More women experienced pain relief, and fewer had additional pain relief, with paracetamol compared with placebo, although potential adverse effects were not assessed and generally the quality of studies was unclear.

Augmentation of acetaminophen analgesia by the antihistamine phenyltoloxamine.

A double-blind, placebo-controlled, parallel-group study was performed to compare the analgesic activity of the combination of 650 mg acetaminophen plus 60 mg phenyltoloxamine citrate with that of 650 mg acetaminophen alone. Two hundred female inpatients who had severe pain associated with a recent episiotomy procedure were randomly assigned to receive a single dose of one of the two active treatments or a placebo. Analgesia was assessed over a 6-hour period. Treatments were compared on the basis of standard subjective scales for pain intensity and relief, a number of derived variables based on these data and two global measures. For essentially all measures, the two active treatments were significantly superior to the placebo control. The combination was significantly superior to acetaminophen alone for all analgesic measures including SPID, TOTAL, and global ratings. The results of this study demonstrate that 60 mg phenyltoloxamine produces significant augmentation of the analgesic activity of 650 mg acetaminophen in postepisiotomy pain.

CD008407

More women experienced pain relief, and fewer had additional pain relief, with paracetamol compared with placebo, although potential adverse effects were not assessed and generally the quality of studies was unclear.

Acetaminophen versus propoxyphene hydrochloride for relief of pain in episiotomy patients.

CD008407

More women experienced pain relief, and fewer had additional pain relief, with paracetamol compared with placebo, although potential adverse effects were not assessed and generally the quality of studies was unclear.

[Analgesic effect of ibuprofen in pain after episiotomy].

The relief of post-episiotomy pain was investigated in three groups of women, ranked ASA 1 or 2, using either a single dose of 400 mg of ibuprofen (n = 31), or 1 g of paracetamol (n = 28) or placebo (n = 31). Pain intensity was assessed with a visual analogic scale, a verbal scale and pain relief scores after half an hour, 1, 2, 3, 4, 5 and 6 h. The day after treatment, patients rated the quality of pain relief, and were asked whether they wished to take again the same drug for the same type of pain. In the placebo and paracetamol groups, respectively 22 and 16 patients asked for usual treatment before the sixth hour, whereas only 5 did so in the ibuprofen group (p less than 0.001). Ibuprofen was more effective after one hour than either of the other two drugs, whatever the scale or parameter used. In the ibuprofen group, the lower pain score was observed at the third hour. At six hours, the pain score did not differ from that three hours earlier. On the day after treatment, 22 patients from the ibuprofen group considered pain relief to have been good or excellent, versus 8 and 5 in the paracetamol and placebo groups respectively (p less than 0.001). Similarly, 24 patients from the ibuprofen group would accept the same drug again for the same type of pain, as opposed to 8 and 5 from the paracetamol and placebo groups respectively (p less than 0.01). The only side-effect reported was abdominal pain in one patient (placebo group).(ABSTRACT TRUNCATED AT 250 WORDS)

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

[Fluoxetine versus fluvoxamine for treatment of chronic pain].

This study aimed: 1) to compare the analgesic efficacy and profile of two antidepressants with the same mechanism of action (SSRI: selective serotonine reuptake inhibitors): fluoxetine vs fluvoxamine; 2) to investigate the relationship between analgesic efficacy and antidepressant effects in both drugs; 3) to evaluate the relationship between the analgesic profile and the quality (global or neuropathic) of pain. Fifty-three depressed patients were randomly treated with 20 mg/die of fluoxetine and 100 mg/die of fluvoxamine for chronic pain. Forty subjects (20 with fluoxetine and 20 with fluvoxamine) completed the 2-month study and were followed up on day 14, 28 and 56 of treatment. The intensity and quality of pain was assessed using Quid and depression-anxiety symptoms with the Hamilton Rating Scale (HAMD). The intensity and overall quality of pain deteriorated at day 14 in the fluvoxamine group and improved in those treated with fluoxetine. However, a comparable level of analgesia was achieved with both drugs at 2 months. After 2 weeks the neuropathic component of pain improved in patients treated with fluvoxamine. The improvement in pain observed in patients treated with fluoxetine depended on an improvement in depressive symptoms, whereas this relationship was not observed in the fluvoxamine group. Although a comparable level of analgesia was observed after two months of treatment, the two drugs show different analgesic profiles. Their analgesic action appears to depend on different mechanisms.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Gabapentin and venlafaxine for the treatment of painful diabetic neuropathy.

To evaluate the safety and efficacy of gabapentin and venlafaxine in the treatment of painful diabetic neuropathy in patients whose pain did not improve with gabapentin monotherapy. (1) A randomized, double-blind, placebo-controlled, 8-week clinical trial comparing gabapentin versus placebo to define a patient population whose pain did not improve with monotherapy; (2) a second 8-week trial comparing gabapentin plus venlafaxine with gabapentin plus placebo; (3) a third uncontrolled 8-week trial of patients who did not improve on gabapentin monotherapy and then received venlafaxine in addition to gabapentin. (1) Gabapentin-treated patients showed statistically significant improvement in pain reduction as well as improvement in quality of life and mood disturbance when compared with placebo-treated patients; (2) patients who received gabapentin plus venlafaxine showed significant improvement in pain reduction, mood disturbance, and quality of life when compared with patients treated with gabapentin plus placebo; (3) patients who received gabapentin plus venlafaxine showed significant improvement in pain reduction, mood disturbance, and quality of life. (1) Gabapentin is efficacious in the treatment of painful diabetic neuropathy; (2) and (3) in patients who do not respond to gabapentin monotherapy, the addition of venlafaxine is also efficacious.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Nortriptyline and fluphenazine in the symptomatic treatment of diabetic neuropathy. A double-blind cross-over study.

A controlled clinical trial on the efficacy of a nortriptyline-fluphenazine combination was carried out in patients with painful diabetic polyneuropathy. A visual analog scale was used to evaluate the relief of pain or paresthesia. Significant relief of both pain and paresthesia was obtained with this combination. The differences were statistically significant. Side effects were frequent but not usually severe enough to lead to cessation of these medications.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Atypical facial pain and depression.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Amitriptyline versus placebo in postherpetic neuralgia.

To study the effects of amitriptyline in treating postherpetic neuralgia, 24 patients were randomly assigned to either drug or placebo in a double-blind crossover study. We found good to excellent pain relief in 16 of 24 patients (p less than or equal to 0.001). We did not find an antidepressant effect in most patients (p greater than 0.05). The median dose of amitriptyline was 75 mg. The median blood level was 65 ng per milliliter, and of nortriptyline 30 ng per milliliter. Good responses were maintained in 12 of 22 patients. Amitriptyline is useful in treating postherpetic neuralgia and may not act as an antidepressant.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Clomipramine vs desipramine vs placebo in the treatment of diabetic neuropathy symptoms. A double-blind cross-over study.

1. The effect of clomipramine and desipramine on diabetic neuropathy symptoms was examined in a double-blind, randomised, placebo controlled, cross-over study for 2 + 2 + 2 weeks. Drug doses were adjusted according to the sparteine phenotype, i.e. extensive metabolisers were treated with 75 mg clomipramine day-1 and 200 mg desipramine day-1 whereas poor metabolisers were treated with 50 mg day-1 of both drugs. Nineteen patients completed the study. 2. Plasma concentration of clomipramine plus desmethylclomipramine was 70-510 nM in extensive metabolisers, vs 590 and 750 nM in two poor metabolisers. Desipramine levels were 130-910 nM, vs 860 and 880 nM. 3. Both clomipramine and desipramine significantly reduced the symptoms of neuropathy as measured by observer- and self rating in comparison with placebo. Clomipramine tended to be more efficacious than desipramine. Patients with a weak or absent response on clomipramine had lower plasma concentrations (clomipramine plus desmethyl-clomipramine less than 200 nM) than patients with a better response. For desipramine a relationship between plasma concentration and effect was not established. 4. Side effect ratings did not differ for clomipramine and desipramine and on both drugs three patients withdrew due to side effects. 5. Compared with earlier results obtained with imipramine dosed on the basis of plasma level monitoring, clomipramine and desipramine on fixed doses appeared less efficacious whereas the side effect profiles were the same. At least for clomipramine, appropriate dose adjustment on the basis of plasma level monitoring may increase the efficacy.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Imipramine treatment of painful diabetic neuropathy.

Twelve patients with severe, painful diabetic neuropathy in the lower extremities were treated with imipramine and placebo in a fixed-dose, double-blind, crossover study of five plus five weeks. Seven patients experienced notable improvement while receiving imipramine and none while receiving placebo. The rating of specific symptoms at the end of each treatment period showed a beneficial effect of imipramine on pain, paresthesia, dysesthesia, numbness, and nocturnal aggravation. The plasma levels of imipramine and its metabolite desipramine were significantly higher in patients who benefited from imipramine treatment.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Clomipramine and amitriptyline in the treatment of severe pain.

Clomipramine is the most potent 5-HT reuptake blockade agent among the antidepressants. A comparison between the effect of clomipramine and a less powerful 5-HT reuptake blockade agent (amitriptyline) could test the hypothesis that brain 5-HT is a mediator of pain sensation. Groups of patients of either sex, with pain indication of trigeminal neuralgia, tension headache or postherpatic neuralgia, received doses of clomipramine or amitriptyline in a single blind clinical experiment. The results after three months of treatment showed that clomipramine: (1) was better than amitriptyline in treating trigeminal neuralgia; (2) tended to be better in the treatment of tension headache; and (3) amitriptyline is better in treating postherpatic neuralgia. Clomipramine was better tolerated. The results support the hypothesis that in certain pain situations, clomipramine exerts a beneficial effect, not only because of its effect on the depression and anxiety level of the patient, but also via its effects on the 5-HT brain system.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

A comparison a amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics.

To compare amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics. A double-blind, crossover trial of treatment with amitriptyline, maprotiline, and placebo. Treatment was given in randomized order for periods of 4 weeks. Each period was separated by a 1-week washout. The final dose was 75 mg/day for both amitriptyline and maprotiline. Thirty-seven patients with diabetic and nondiabetic painful polyneuropathy. The treatment effects were assessed by daily ratings of pain intensity on a 10-step verbal scale (0 = no pain and 10 = worst thinkable pain) and at the end of each treatment period by a global rating of the analgesic effect on a 5-step verbal scale (pain relief scale). For the assessment of depression, the Comprehensive Psychopathological Rating Scale (CPRS) was used. Using the global assessment of pain relief at the end of each treatment period, 22 of 33 patients reported reduced pain on amitriptyline treatment compared with 14 of 33 patients on maprotiline treatment and 8 patients on placebo treatment (p < .0001 and p < .05 for amitriptyline and maprotiline, respectively, against placebo). Amitriptyline was slightly better than maprotiline (p < .05) [tested by repeated measures analysis of variance (ANOVA)]. The order in which treatments occurred and the diagnosis of diabetes or nondiabetes did not have any significant effect on the global rating of pain relief. The mean values of the daily ratings of pain intensity showed that pain was more severe in the evenings than in the mornings and that diabetic patients reported worse pain than nondiabetics at baseline. The mean values of pain reduction as assessed with the 10-step verbal scale during the 4th week of treatment showed that amitriptyline and maprotiline were significantly better than placebo in relieving the pain (p < .0001 and p < .01, respectively, post hoc test according to Scheffé). However, there was no significant difference between the pain reduction of amitriptyline compared with maprotiline when assessing pain reduction with the 10-step verbal scale during the 4th treatment week. Nor was there a significant difference between diabetics and nondiabetics with regard to the effect of the drugs. The clinical effect was not significantly correlated to plasma concentration of either amitriptyline and its active metabolite nortriptyline or maprotiline in the global or daily assessments. The effect of treatment was not correlated to any particular pain quality nor to the intensity of pain. Depression was noted in three patients who completed the medication trial, but the effect of treatment of pain and depression did not clearly correlate. The adverse side effects of amitriptyline and maprotiline were common, and in 5 patients the medication had to be discontinued because of severe side effects. From the present results and the literature, it is concluded that tricyclic antidepressants with a pharmacologic profile similar to amitriptyline are the most effective drugs in the treatment of polyneuropathy pain in both diabetic and nondiabetic patients.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy.

The effect of the selective serotonin reuptake inhibitor citalopram on diabetic neuropathy symptoms was examined in a double-blind, placebo-controlled, crossover study for two 3-week periods. Citalopram was given as a fixed dose of 40 mg/day. Data from 15 patients could be included in the statistical analysis. Citalopram significantly relieved the symptoms of neuropathy as measured by both observer- and self-rating in comparison with placebo. The steady-state plasma concentration of citalopram was 10 to 890 nmol/L. There was no significant relationship between the plasma concentration of citalopram and the effect of treatment as measured by observer- or self-rating. Two of 17 patients, both receiving citalopram, left the study because of side effects (nausea and vomiting or gastric upset and diarrhea). Side-effect ratings were significantly higher during administration of citalopram than during administration of placebo, but citalopram was generally well tolerated. Compared with earlier results obtained with imipramine administered on the basis of plasma level monitoring, citalopram appeared to be less effective, but seemed to be better tolerated.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Lack of effect of mianserin on the symptoms of diabetic neuropathy.

The effect of the non-tricyclic antidepressant mianserin on symptoms of diabetic neuropathy has been studied in 18 patients in a double-blind, cross-over study with imipramine as a positive control. The patients were treated with placebo, mianserin, and imipramine, each for two weeks, in randomized order, with 1-3 weeks between the treatments. The symptoms were assessed by observer and self-rating scales. Mianserin was given in the fixed dosage of 60 mg per day, whereas the dose of imipramine was adjusted to yield the optimal plasma concentration of imipramine plus desipramine of 400-600 nmol.l-1. The mianserin plus desmethylmianserin plasma concentration ranged from 85 to 850 nmol.l-1, with the highest concentration in a patient who was a poor metabolizer of both sparteine and mephenytoin. The symptoms of neuropathy were significantly reduced during imipramine treatment, although somewhat less than in earlier studies. In contrast, mianserin produced no change in symptoms in comparison with placebo. As there was no evidence that higher mianserin (plus metabolite) steady-state concentrations were associated with a more favourable effect, the negative outcome appeared not to be related to underdosing with mianserin. In contrast to drugs with documented effects on the symptoms of diabetic neuropathy, mianserin has a very weak or no inhibitory effect on 5-HT and noradrenaline reuptake and this may explain its poor clinical effect.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Venlafaxine in the treatment of atypical facial pain: a randomized controlled trial.

To study in a randomized placebo-controlled design the efficacy of the antidepressant venlafaxine, a serotonin and a weak noradrenaline reuptake inhibitor, in the treatment of atypical facial pain (AFP). The study was a randomized, double-blind, crossover comparison of venlafaxine and a placebo. It consisted of 2 treatment periods, each of 4 weeks' duration, separated by a 2-week washout period. Thirty patients suffering from chronic pain who had been diagnosed with AFP after a thorough clinical examination were recruited. Pain intensity and pain relief were registered at 6 visits. Anxiety, depression, and adverse effects were recorded. Venous blood samples were collected at the end of each treatment period for the determination of serum levels of venlafaxine and its metabolites. Twenty patients completed the trial. Eight patients discontinued because of adverse effects and 2 patients were excluded because of noncompliance. Two patients completed the trial but were excluded from the analysis because they experienced no pain at the baseline visit. There was no significant difference in pain intensity reduction between the maximum tolerated dose of venlafaxine (75 mg in most cases) and the placebo. Pain relief was significantly greater with venlafaxine than with the placebo treatment. Significantly more escape medication was consumed during the placebo period compared with the venlafaxine period. No significant correlation was found between the serum concentration of the drug and the response to treatment. Anxiety and depression scores did not differ between venlafaxine and placebo treatment. Adverse effects were equally common during both treatments. Venlafaxine was only modestly effective in the treatment of AFP.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Venlafaxine versus imipramine in painful polyneuropathy: a randomized, controlled trial.

Tricyclic antidepressants (TCA) are often used in the treatment of painful polyneuropathy. Venlafaxine is a serotonin and weak noradrenaline reuptake inhibitor antidepressant with a different profile of other pharmacologic actions from those of TCA. To test if venlafaxine would relieve painful polyneuropathy and compare its possible efficacy with that of the TCA imipramine. The study design was randomized, double blind, and placebo controlled, with a three-way crossover. Forty patients were assigned to one of the treatment sequences, and 29 completed all three study periods. The daily doses were venlafaxine 225 mg and imipramine 150 mg. During the three treatment periods, each of 4 weeks' duration, patients rated pain paroxysms, constant pain, and touch- and pressure-evoked pain by use of 0- to 10-point numeric rating scales. The sum of the individual pain scores during treatment week 4 was lower on venlafaxine (80% of baseline score; p = 0.006) and imipramine (77%; p = 0.001) than on placebo (100%) and did not show any statistical difference between venlafaxine and imipramine (p = 0.44). The individual pain scores for pain paroxysms, constant pain, and pressure-evoked pain showed a similar pattern, whereas touch-evoked pain was uncommon and was not altered by any of the drugs. Numbers needed to treat to obtain one patient with moderate or better pain relief were 5.2 for venlafaxine and 2.7 for imipramine. Venlafaxine relieves pain in polyneuropathy and may be as effective as imipramine.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Gabapentin vs. amitriptyline in painful diabetic neuropathy: an open-label pilot study.

The objective of this study was to compare the efficacy and tolerability of gabapentin and amitriptyline monotherapy in painful diabetic neuropathy. This was a 12-week, open-label, prospective, randomized trial. Twenty-five type-II diabetic patients with pain attributed to diabetic neuropathy and a minimum score of 2 on a pain intensity scale ranging from 0 (no pain) to 4 (excruciating pain) were randomized to receive either gabapentin, titrated from 1,200 mg/day to a maximum of 2,400 mg/day, or amitriptyline, titrated from 30 mg/day to a maximum of 90 mg/day. Both drugs were titrated over a 4-week period and maintained at the maximum tolerated dose for 8 weeks. The main outcome measures were weekly pain intensity and paresthesia intensity, measured on two categorical scales. Thirteen patients received gabapentin and 12 received amitriptyline. All 25 patients completed the trial. Gabapentin produced greater pain reductions than amitriptyline (mean final scores were 1.9 vs. 1.3 points below baseline scores; P = 0.026). Decreases in paresthesia scores also were in favor of gabapentin (1.8 vs. 0.9 points; P = 0. 004). Adverse events were more frequent in the amitriptyline group than in the gabapentin group: they were reported by 11/12 (92%) and 4/13 (31%) of patients, respectively (P = 0.003). Side effects were the main limiting factor preventing dose escalation. Gabapentin produced greater improvements than amitriptyline in pain and paresthesia associated with diabetic neuropathy. Additionally, gabapentin was better tolerated than amitriptyline. Further controlled trials are needed to confirm these preliminary results.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

St. John's wort has no effect on pain in polyneuropathy.

Tricyclic antidepressants are the mainstay of treatment of painful polyneuropathy but cannot be used in a substantial number of patients. St. John's wort is a herbal antidepressant, which may act via mechanisms similar to the tricyclics. The aim of this study was to test if St. John's wort would relieve painful polyneuropathy. The study design was randomized, double-blind, placebo-controlled and cross-over. Fifty-four patients were assigned to one of the two treatment sequences. The daily dose of St. John's wort was three tablets each containing 900 microg totalhypericin. During the two treatment periods of 5 weeks duration, patients rated constant pain, lancinating pain paroxysms, touch-evoked pain and pain on pressure by use of 0--10 point numeric rating scales. Forty-seven patients -- 18 diabetics and 29 non-diabetics -- completed the study. There was a trend of lower total pain score (sum of the individual pain scores) on St. John's wort than on placebo (median 14 vs. 15, P=0.05). None of the individual pain ratings were significantly changed by St. John's wort as compared to placebo (P=0.09--0.33). Complete, good or moderate pain relief was experienced by nine patients with St. John's wort and two with placebo (P=0.07). In conclusion, St. John's wort has no significant effect on pain in polyneuropathy.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

The analgesic effect of amitriptyline on chronic facial pain.

The efficacy of amitriptyline was evaluated in 28 patients with chronic oral-facial pain. Most of the patients had evidence of musculoskeletal pain while some had a history suggesting pain of neurogenic origin. Two patients had mixed elements of neurogenic and musculoskeletal pain. Amitriptyline was more effective than placebo in reducing pain after 4 weeks of treatment. No effect was found after only 1 week of drug administration in either dose range. When the patients were divided into depressed and non-depressed groups based on their Hamilton depression scores, amitriptyline reduced pain in the depressed and in the non-depressed groups as compared to placebo. Amitriptyline reduced the depression scores in the depressed group but had no effect on the depression scores in the non-depressed group. Thus, pain reduction was not associated with a change in mood in the non-depressed group. Amitriptyline had no effect on patients' ratings of the intensity of experimental heat stimuli. We conclude that amitriptyline is effective in the treatment of chronic oral-facial pain and that its efficacy is independent of its effects on depression. It appears that tricyclic antidepressants act in a fashion different from opiate drugs that alter the sensory discriminative component of pain.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: a randomized controlled trial. Terry Beirn Community Programs for Clinical Research on AIDS.

Peripheral neuropathy is common in persons infected with the human immunodeficiency virus (HIV) but few data on symptomatic treatment are available. To evaluate the efficacy of a standardized acupuncture regimen (SAR) and amitriptyline hydrochloride for the relief of pain due to HIV-related peripheral neuropathy in HIV-infected patients. Randomized, placebo-controlled, multicenter clinical trial. Each site enrolled patients into 1 of the following 3 options: (1) a modified double-blind 2 x 2 factorial design of SAR, amitriptyline, or the combination compared with placebo, (2) a modified double-blind design of an SAR vs control points, or (3) a double-blind design of amitriptyline vs placebo. Terry Beirn Community Programs for Clinical Research on AIDS (HIV primary care providers) in 10 US cities. Patients with HIV-associated, symptomatic, lower-extremity peripheral neuropathy. Of 250 patients enrolled, 239 were in the acupuncture comparison (125 in the factorial option and 114 in the SAR option vs control points option), and 136 patients were in the amitriptyline comparison (125 in the factorial option and 11 in amitriptyline option vs placebo option). Standardized acupuncture regimen vs control points, amitriptyline (75 mg/d) vs placebo, or both for 14 weeks. Changes in mean pain scores at 6 and 14 weeks, using a pain scale ranging from 0.0 (no pain) to 1.75 (extremely intense), recorded daily. Patients in all 4 groups showed reduction in mean pain scores at 6 and 14 weeks compared with baseline values. For both the acupuncture and amitriptyline comparisons, changes in pain score were not significantly different between the 2 groups. At 6 weeks, the estimated difference in pain reduction for patients in the SAR group compared with those in the control points group (a negative value indicates a greater reduction for the "active" treatment) was 0.01 (95% confidence interval [CI], -0.11 to 0.12; P=.88) and for patients in the amitriptyline group vs those in the placebo group was -0.07 (95% CI, -0.22 to 0.08; P=.38). At 14 weeks, the difference for those in the SAR group compared with those in the control points group was -0.08 (95% CI, -0.21 to 0.06; P=.26) and for amitriptyline compared with placebo was 0.00 (95% CI, -0.18 to 0.19; P=.99). In this study, neither acupuncture nor amitriptyline was more effective than placebo in relieving pain caused by HIV-related peripheral neuropathy.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a randomized placebo-controlled, double-blind crossover study.

Amitriptyline is the most common analgesic adjuvant used in cancer patients with neuropathic pain, even though no specific studies have demonstrated a benefit. A randomized placebo-controlled, double-blind crossover study was designed to evidence the effects of amitriptyline in patients with neuropathic cancer pain. Sixteen advanced cancer patients with neuropathic pain on systemic morphine therapy, no longer receiving oncologic treatment, presenting moderate pain (about 4 or more, but less than 7, on a numerical scale of 0-10) in the last week, and given a stable morphine dose in the last 2 days were admitted to the study. During the first week of study, patients were administered 25 mg of amitriptyline or equivalent drops of placebo at night for 3 days and 50 mg for the following 4 days. Doses for patients aged more than 65 years were 15 mg (first 3 days) and 30 mg (3 days after). After a week, a crossover took place for the second week, with the other treatment at an inverse sequence. Opioid consumption, pain intensity, symptoms and adverse effects, mood, sleep, patient's preference, quality of life before starting the study, the first week after and the second week after were recorded. No significant benefits in analgesia were found in the global pain intensity of the previous week of treatment, the least pain intensity or the pain evaluated just after a week of treatment, at the moment of the visit, when amitriptyline was compared with placebo. A significant difference was evidenced for the worst pain (P < 0.035). No differences in opioid doses during the period of study were found. Drowsiness, confusion and dry mouth were significantly more intense with amitriptyline than with placebo (P < 0.036, 0.003, and 0.034, respectively). There were no substantial differences between the two treatments in Spitzer's quality of life score and for each item. No differences in patients' preference for the two treatment periods were found. The analgesic effects of amitriptyline were slight and associated with adverse effects. In light of the results obtained in the study, the extensive use of the drug for cancer pain should be questioned.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Venlafaxine in neuropathic pain following treatment of breast cancer.

Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer. However, adverse effects are a major problem. Venlafaxine has no anticholinergic effects and could have a better compliance. The aim of the study was to evaluate the effectiveness of venlafaxine in neuropathic pain. The study was a randomized, double-blind, crossover comparison of venlafaxine and inactive placebo. The study lasted 10 weeks. The number of tablets (18.75 mg) taken daily was increased by one at a 1 week interval. Pain intensity and pain relief were registered daily by a diary and by a questionnaire and a computer program (Painscreen) on each visit. Adverse effects were evaluated with the diaries and a 10-item list on each visit. Also, anxiety and depression were measured on each visit. Venous blood samples were collected before the treatment and at 4 weeks for the determination of the serum levels of venlafaxine and its three metabolites. Thirteen patients were analysed. The average daily pain intensity as reported in the diary (primary outcome) was not significantly reduced by venlafaxine compared with placebo. However, the average pain relief (diary) and the maximum pain intensity (retrospective assessment by the computer program) were significantly lower with venlafaxine compared with placebo. Anxiety and depression were not affected. Adverse effects did not show significant differences between treatments. The two poor responders had low venlafaxine concentrations whereas the two slow hydroxylizers had high venlafaxine concentrations and excellent pain relief. Thus, higher doses could be used in order to improve pain relief. Copyright 2002 European Federation of Chapters of the International Association for the Study of Pain

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Trazodone hydrochloride in the treatment of dysesthetic pain in traumatic myelopathy: a randomized, double-blind, placebo-controlled study.

Dysesthetic pain following traumatic myelopathy is characterized by diffuse burning and tingling sensations distal to the level of spinal injury. The dysesthetic pain syndrome (DPS) can compromise performance of functional abilities and inhibit participation in rehabilitation programs. Recent laboratory evidence suggests that antidepressant medications with selective inhibition of serotonin reuptake in the brain may be associated with superior analgesic effect compared to such non-selective agents as amitriptyline. Trazodone hydrochloride is a potent presynaptic serotonin reuptake blocker with few anticholinergic and cardiovascular side effects. This study was a randomized, double-blind, placebo-controlled trial of trazodone hydrochloride for the treatment of DPS. Following a 2-week placebo lead-in period, patients were randomized to a 6-week course of 150 mg trazodone hydrochloride/day or placebo. Evaluations of pain quality and intensity were performed at 2-week intervals, utilizing the McGill Pain Questionnaire, Sternbach Pain Intensity Scale, and Zung Pain and Distress Index. Neurologic examination and assessment of side effects were performed at each evaluation session. No significant changes were noted in reported pain measures between patients allocated to the active drug group and those given placebo during the course of the protocol. However, significantly more patients randomized to trazodone complained of side effects and prematurely terminated their participation in the study. The results of this investigation are consistent with those of other earlier trials which indicate that such antidepressant medications as trazodone hydrochloride which selectively inhibit presynaptic reuptake of serotonin, may not be effective in the control of certain pain syndromes. These results do not preclude the possible utility of these agents in the treatment of other pain syndromes or at higher doses than previously studied.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Amitriptyline and fluphenazine in the treatment of postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a vexing problem occurring in 10 to 20 percent of people with from herpes zoster (shingles). Anecdotal reports show that fluphenazine enhances the effects of amitriptyline for the treatment of PHN. The aim of this study was to determine, in a controlled manner, whether this was the case. In a double-blind placebo-controlled study, 49 patients with PHN were randomly assigned to four treatment groups: Group 1, amitriptyline; Group 2, amitriptyline and fluphenazine; Group 3, fluphenazine; Group 4, a placebo. An active placebo was used to mimic the anticholinergic side effects of dry mouth. The study lasted 8 weeks, with weekly progress evaluations with use of visual analog scales (VAS), the McGill Pain Questionnaire (MPQ), and a side-effects scale. A statistically significant decrease was seen in pain in Groups 1 and 2, and no significant changes were seen in Groups 3 and 4. There was no significant difference when fluphenazine was added to amitriptyline. These data support the effectiveness of amitriptyline in treatment of PHN, but do not support the addition of fluphenazine.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Depression masquerading as diabetic neuropathy.

Fifty-nine patients referred for painful diabetic neuropathy of the lower extremities were evaluated for depression and response to antidepressant drug therapy in a double-blind controlled study. All patients were found to have substantial degrees of depression during psychiatric interview and by Kupfer-Detre test scores (8.1 +/- 0.6, as compared with control values of 4.0 to 4.3 +/- 0.2). Treatment with imipramine hydrochloride or amitriptyline hydrochloride resulted in complete remission of lower extremity pains in all patients in 10 +/- 2 weeks, with concomitant relief of depression and return of depression test scores to 3.8. These results suggest that the syndrome of painful diabetic neuropathy of the lower extremities represents a depressive equivalent in a large proportion of cases and that treatment with imipramine or amitriptyline is a successful mode of therapy for such persons.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Trazodone in burning mouth pain: a placebo-controlled, double-blind study.

An 8-week parallel, placebo-controlled, double-blind trial evaluated the efficacy of the antidepressant trazodone in the treatment of chronic burning mouth pain. Thirty-seven carefully selected women aged 39 to 71 (mean 58.6 years) were randomized to receive either 200 mg of trazodone or a placebo in a similar manner. Pain and pain-related symptoms were evaluated on a visual analogue scale and other measures at 0, 2, 4, and 8 weeks. There were no significant differences between the groups in treatment effects for pain or pain-related symptoms. Seven patients in the trazodone group and 2 in the placebo group failed to complete the trial because of side effects. The most common side effects were dizziness and drowsiness. In this controlled trial, trazodone failed to relieve burning mouth pain.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Amitriptyline in the prophylaxis of central poststroke pain. Preliminary results of 39 patients in a placebo-controlled, long-term study.

We performed a double-blind, placebo-controlled study to investigate the effectiveness of amitriptyline for the prophylactic treatment of patients with acute thalamic stroke in preventing central poststroke pain. Subject received, in a randomized sequence, either amitriptyline titrated from 10 to 75 mg in extended-release form or placebo over a therapy period of 365 days. We documented the time when pain developed; the intensity, type, site, and distribution of pain; and the presence/absence and type of allodynia. Thirty-nine patients (23 women and 16 men; age range, 36 to 68 years) with central poststroke pain participated. The placebo group showed a pain rate of 21% within 1 year after the diagnosis of thalamic stroke compared with 17% in the group under prophylactic treatment with amitriptyline. Average (SE) time to pain was 318 (23) days for patients in the placebo group and 324 (24) days for patients in the amitriptyline group. With the achieved sample sizes of this study and a pain rate of approximately 21% in the placebo group, any near-perfect pain protection would have been detected. Near-perfect pain protection, in this context, refers to pain in <2.4% of the recruited patients treated with amitriptyline or in approximately 89% of placebo-treated patients. Larger studies are recommended to test the hypothesis that prophylactic amitriptyline reduces but does not completely prevent central poststroke pain.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Amitriptyline, but not lorazepam, relieves postherpetic neuralgia.

In a double-blind, randomized, crossover study, 58 patients with postherpetic neuralgia received 6-week courses of amitriptyline, 12.5 to 150 mg/d; lorazepam, 0.5 to 6 mg/d; or lactose placebo. Doses were titrated to the maximum level tolerated. Patients rated pain in a diary, using lists of verbal descriptors. Forty-seven percent of patients reported moderate or greater relief with amitriptyline, 16% with placebo, and 15% with lorazepam. Mean amitriptyline dose was 65 mg/d. Greater relief was associated with higher amitriptyline doses, up to the maximum dose of 150 mg/d, and with higher serum tricyclic levels. Lorazepam did not relieve pain and was associated with severe depressive reactions in four patients.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

The effects of pre-emptive treatment of postherpetic neuralgia with amitriptyline: a randomized, double-blind, placebo-controlled trial.

Seventy-two patients older than 60 years of age who received a diagnosis of herpes zoster (HZ) were entered into a randomized, double-blind, placebo-controlled trial of daily amitriptyline 25 mg. Treatment with either amitriptyline or placebo continued for 90 days after diagnosis. Pain prevalence at 6 months was the primary outcome. Results showed that early treatment with low-dose amitriptyline reduced pain prevalence by more than one-half (p < 0.05; odds ratio, 2.9:1) This finding makes a strong case for the pre-emptive administration of amitriptyline, in combination with an antiviral drug, to elderly patients with acute herpes zoster.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Efficacy of amitriptyline for relief of pain in spinal cord injury: results of a randomized controlled trial.

Chronic pain in persons with spinal cord injury (SCI) is a difficult problem for which there is no simple method of treatment. Few randomized controlled trials of medications for pain in persons with SCI have been conducted. This study was designed to determine whether amitriptyline, a tricyclic antidepressant, is efficacious in relieving chronic pain and improving pain-related physical and psychosocial dysfunction in persons with SCI. Eighty-four participants with SCI and chronic pain were randomized to a 6-week trial of amitriptyline or an active placebo, benztropine mesylate. All pre- and post-treatment assessments were conducted by evaluators blind to the allocation. Regression analyses were conducted to examine whether there was a medication group effect on the primary (average pain intensity) and secondary outcome measures. No significant differences were found between the groups in pain intensity or pain-related disability post-treatment, in either intent-to-treat analyses or analyses of study completers. These findings do not support the use of amitriptyline in the treatment of chronic pain in this population, but we cannot rule out the possibility that certain subgroups may benefit.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy.

Amitriptyline reduces the pain caused by peripheral-nerve disease, but treatment is often limited by side effects related to the drug's many pharmacologic actions. Selective agents might be safer and more effective. We carried out two randomized, double-blind, crossover studies in patients with painful diabetic neuropathy, comparing amitriptyline with the relatively selective blocker of norepinephrine reuptake desipramine in 38 patients, and comparing the selective blocker of serotonin reuptake fluoxetine with placebo in 46 patients. Fifty-seven patients were randomly assigned to a study as well as to the order of treatment, permitting comparison among all three drugs and placebo as the first treatment. The patients rated the degree of pain present each day using verbal descriptors, and they also assessed the extent of pain relief globally at the end of each treatment period. After individual dose titration, the mean daily doses of the drugs were as follows: amitriptyline, 105 mg; desipramine, 111 mg; and fluoxetine, 40 mg. There was moderate or greater relief of pain in 28 of the 38 patients (74 percent) who received amitriptyline, 23 of the 38 patients (61 percent) who received desipramine, 22 of the 46 patients (48 percent) who received fluoxetine, and 19 of the 46 patients (41 percent) who received placebo. The differences in responses between amitriptyline and desipramine and between fluoxetine and placebo were not statistically significant, but both amitriptyline and desipramine were superior to placebo. Amitriptyline and desipramine were as effective in patients who were not depressed as in depressed patients, but fluoxetine was effective only in depressed patients. Desipramine relieves pain caused by diabetic neuropathy with efficacy similar to that of amitriptyline, offering an alternative for patients unable to tolerate the latter. Blockade of norepinephrine reuptake is likely to mediate the analgesic effect of these antidepressant drugs in diabetic neuropathy. Fluoxetine, which blocks serotonin uptake, is no more effective than placebo for the relief of pain.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team.

Painful sensory neuropathy is a common complication of HIV infection. Based on prior uncontrolled observations, we hypothesized that amitriptyline or mexiletine would improve the pain symptoms. A randomized, double-blind, 10-week trial of 145 patients assigned equally to amitriptyline, mexiletine, or matching placebo. The primary outcome measure was the change in pain intensity between baseline and the final visit. The improvement in amitriptyline group (0.31+/-0.31 units [mean+/-SD]) and mexiletine group (0.23+/-0.41) was not significantly different from placebo (0.20+/-0.30). Both interventions were generally well tolerated. Neither amitriptyline nor mexiletine provide significant pain relief in patients with HIV-associated painful sensory neuropathy.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Comparative efficacy of SSRIs and amisulpride in burning mouth syndrome: a single-blind study.

Although a significant amount of evidence indicates the efficacy of some antidepressants in treating psychogenic pain and somatoform disorder, very few studies have investigated their possible therapeutic action in burning mouth syndrome (BMS). The purpose of this 8-week, single-blind study was to provide preliminary data on the efficacy and tolerability of amisulpride and the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline for patients with BMS. Seventy-six patients with BMS (diagnosed according to the criteria in the literature and integrating the Diagnostic Interview Schedule-Revised for a complete psychiatric assessment), with no possible local or systemic causes and without concurrent major depression, were randomly assigned to receive amisulpride (50 mg/day), paroxetine (20 mg/day), or sertraline (50 mg/day). Efficacy assessments included a visual analogue scale (VAS) for pain intensity, the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), and the Clinical Global Impressions scale (CGI). All 3 treatment regimens resulted in a significant improvement from baseline in burning mouth symptoms at week 8 as demonstrated by the quantitative (mean reduction in VAS, HAM-D, and HAM-A scores) and qualitative (percentage of responders) analyses. Amisulpride showed a shorter response latency than the SSRIs. No serious adverse events were reported, and the incidence of side effects did not differ among the 3 groups. None of the patients who received amisulpride withdrew from the trial, whereas withdrawal from the trial occurred within the first week of treatment in 11.5% of patients (N = 3) treated with paroxetine and in 21.7% of patients (N = 5) treated with sertraline. The data suggest that amisulpride and SSRIs may be effective treatments for BMS; they are equally effective and equally well tolerated in the short-term treatment of BMS. Amisulpride is associated with better compliance within the first week of treatment and with a shorter response latency in comparison with SSRIs. This finding may indicate that amisulpride is especially useful at the beginning of drug therapy of BMS. Double-blind, placebo-controlled trials are needed to further document the efficacy of amisulpride and SSRIs in the treatment of BMS.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Nortriptyline versus amitriptyline in postherpetic neuralgia: a randomized trial.

OBJECTIVE (BACKGROUND): Amitriptyline (AT) is a standard therapy for postherpetic neuralgia (PHN). Our hypothesis was that nortriptyline (NT), a noradrenergic metabolite of AT, may be more effective. A randomized, double-blind, crossover trial of AT versus NT was conducted in 33 patients. Thirty-one patients completed the trial. Twenty-one of 31 (67.7%) had at least a good response to AT or NT, or both. We found no difference with regard to relief of steady, brief, or skin pain by visual analog scales for pain and pain relief; mood; disability; satisfaction; or preference between the two drugs. Intolerable side effects were more common with AT. Most patients (26/33) were not depressed, and most responding showed no change in rating scales for depression despite the occurrence of pain relief. We concluded that this study provides a scientific basis for an analgesic action of NT in PHN because pain relief occurred without an antidepressant effect, and that although there were fewer side effects with NT, AT and NT appear to have a similar analgesic action for most individuals.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Nortriptyline-fluphenazine vs. carbamazepine in the symptomatic treatment of diabetic neuropathy.

We compared the efficacy and tolerance of the combination of nortriptyline-fluphenazine (NF) vs. carbamazepine (CMZ) in the symptomatic therapy of patients with severe, distal, symmetrical, predominantly sensitive diabetic polyneuropathy (DPN). We followed a double blind, crossover, randomized and double placebo design. Sixteen patients with severe DPN participated in the study. Patients received either NF (1 tablet three times a day (tid)), for 2 weeks and 2 tablets tid for the next 2 weeks or CMZ 1/2 tablet tid for 2 weeks and 1 tablet tid for the next 2 weeks. After this, patients received placebos of both drugs (wash-out period), until symptoms returned to baseline levels (100%), then they were crossed over to receive the other comparing drug schedule. A visual analogue scale was used to evaluate the percent changes in pain and paresthesia. HbA1, fasting serum glucose, and safety tests were performed at 2- and 4-week intervals, respectively. Both therapies produced significant improvement of both pain and paresthesia. No statistically significant differences were observed between both therapies for either pain or paresthesia. No significant biochemical changes were observed with any of the two therapies. Side effects were mild and more frequent in the NF period. In this study no superiority of either drug schedule was demonstrated; therefore, the decision to use any of them should be made according to the associated pathology and potential side effects of each drug.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Studies on the concomitant use of carbamazepine and clomipramine for the relief of post-herpetic neuralgia.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Amitriptyline versus maprotiline in postherpetic neuralgia: a randomized, double-blind, crossover trial.

Amitriptyline (AT) relieves some patients with postherpetic neuralgia (PHN). Many patients suffer side effects and better therapies are necessary. The aim of this study was to evaluate the efficacy of maprotiline (MT) (noradrenergic) compared to AT (mixed noradrenergic and serotonergic) in this disorder. Thirty-five patients entered a randomized, double-blind, crossover trial of these two agents. We found that MT relieved PHN in many patients but was not as effective as AT. Side effects were troublesome with both agents. Relief of steady pain, brief pain and pain on tactile stimulation occurred. Four groups of responses were identified. Some patients reported relief with both agents, some with neither agent and others with only one of the drugs. Most patients were not depressed and analgesia was observed to occur without change in depression ratings in most patients who responded. This result provides evidence that in some patients AT may act via a selective noradrenergic mechanism in relieving PHN and that individuals may differ in the balance and type of neurotransmitters inhibiting pain. Selective noradrenergic agents may be effective if AT fails.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Distigmine and amitriptyline in the treatment of chronic pain.

Sixty-five patients attending a pain relief clinic were randomly allocated to treatment for 5 weeks with amitriptyline alone, distigmine alone, amitriptyline and distigmine started together, or addition of distigmine to preexisting treatment with amitriptyline. Forty-eight patients successfully completed the trial; the most common cause for withdrawal was dry mouth in the amitriptyline-alone group. Two parameters were measured: Pain intensity was measured at the beginning and end of the treatment, and the saliva flow was measured at the beginning and the end of the treatment. At the end of 5 weeks, treatment with a combination of amitriptyline (75 mg/day) and distigmine (10 mg/day) resulted in a 43% reduction of pain and no subjectively noticeable mouth dryness. Distigmine alone also decreased pain and increased saliva flow, sometimes to the point of discomfort, whereas amitriptyline alone, in this particular series, did not significantly reduce pain and produced unpleasant mouth dryness. The addition of distigmine to preexisting (and ineffective) amitriptyline treatment failed to relieve pain. We therefore conclude that a combination of amitriptyline and distigmine (both given ab initio) may be a useful therapy for chronic pain.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Central post-stroke pain--a controlled trial of amitriptyline and carbamazepine.

A double-blind, 3-phase, cross-over, placebo-controlled trial of the pain-relieving effect of amitriptyline and carbamazepine was carried out in 15 patients with central post-stroke pain (CPSP) but without signs of depression. Treatment was given, in randomized order, for periods of 4 weeks, separated by 1 week wash-out. The final doses were 75 and 800 mg/day, respectively, for amitriptyline and carbamazepine. The treatment effects were assessed by daily ratings of pain intensity on a 10-step verbal scale and at the end of each treatment period by a global rating of the analgesic effect on a 5-step verbal scale. For the assessment of depression the Comprehensive Psychopathological Rating Scale (CPRS) was used. Amitriptyline produced a statistically significant reduction of pain when compared to placebo. According to the global rating, 10 of the 15 patients were responders to this drug. The effect could already be noticed during the second treatment week and it appeared to be correlated to the plasma concentration, since the median total ami- and nortriptyline concentrations were 497 and 247 nmol/l, respectively, for responders and non-responders. The early onset, together with the fact that the patients were not depressed, nor did they obtain reduced scores on ratings of depressive symptoms and signs, provides strong support for the conclusion that the pain relief was not caused by an antidepressive effect. Five of the 14 patients treated with carbamazepine reported some pain relief, but the effect did not reach statistical significance when compared to placebo. No correlation was found between effect and plasma concentration. In general, the patients tolerated the planned final dose of amitriptyline well. No final dose reduction was necessary. Carbamazepine caused more side effects and the final dose had to be reduced in 4 patients. However, only 1 patient had to be taken off medication, on day 25, due to drug interaction.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer.

The effectiveness of amitriptyline in relieving neuropathic pain following treatment of breast cancer was studied in 15 patients in a randomised, double-blind placebo-controlled crossover study. The dose was escalated from 25 mg to 100 mg per day in 4 weeks. The placebo and amitriptyline phases were separated by a 2-week wash-out period. Visual analogue and verbal rating scales were used for the assessment of pain intensity and pain relief. Other measures included the number of daily activities disturbed by the pain, the Finnish McGill Pain Questionnaire, adverse effects, anxiety, depression, pressure threshold and grip strength. Amitriptyline significantly relieved neuropathic pain both in the arm and around the breast scar. Eight out of 15 patients had a more than 50% decrease in the pain intensity ('good responders') with a median dose of 50 mg of amitriptyline. The 7 patients who had a less than 50% effect had drug concentrations equaling those of the good responders. The 'poor responders' reported significantly more adverse effects with amitriptyline and placebo than the good responders. It is concluded that amitriptyline effectively reduced neuropathic pain following treatment of breast cancer. However, the adverse effects of amitriptyline put most of the patients off from using the drug regularly.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study.

The aim of this randomized double blind placebo controlled study was to investigate the effectiveness and the safety of venlafaxine XR 75 and 150 mg on ongoing pain and on quantitative sensory tests in 60 patients with neuropathic pain for 8 weeks. Evaluation parameters consisted of ongoing pain intensity (VAS), patient satisfaction, side effects, global efficacy and tolerance. Quantitative sensory measurements taken from the affected area before and after the drug treatment included pin-prick hyperalgesia, allodynia, detection and pain thresholds to electrical and heat stimuli, temporal summation of repetitive electrical and heat stimuli. A total of 55 patients completed the study. VAS scores decreased significantly compared to the baseline measurements in all groups. There was no significant difference between the groups regarding pain intensity and escape medication. The areas of allodynia and pin-prick hyperalgesia decreased significantly in venlafaxine groups compared to the placebo. There was no significant difference between the groups regarding the detection thresholds (electrical and heat). The pain threshold and the summation threshold to electrical stimuli and the summation threshold to heat stimuli increased significantly following treatment in both venlafaxine groups. In addition, the degree of the temporal summation to electrical and heat stimuli decreased significantly following treatment in both venlafaxine groups compared to the placebo. The study showed significant effect of venlafaxine in the manifestations of hyperalgesia and temporal summation, but not on the ongoing pain intensity. Furthermore, the quantitative sensory tests provided complementing information to the clinical measures.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

[Treatment of post-herpes zoster pain with tramadol. Results of an open pilot study versus clomipramine with or without levomepromazine].

To date, no universally applicable recommendations are available for the treatment of patients with postherpetic neuralgia. A mixture of clinical anecdotes, experimental findings and observations from clinical trials form the basis of the medical arsenal for this condition. Tricyclic antidepressants are commonly used, and clinical experience and several investigations have documented their effectiveness. Today, single entity antidepressants, which can be combined with neuroleptics to increase analgesia, are generally recommended for the treatment of postherpetic neuralgia. Some authors also recommend the additional administration of an opioid if analgesia is inadequate. Just over a decade ago, opioids were considered ineffective for the treatment of neuropathic pain; however, more recent investigations relating to the use of opioids, primarily in the treatment of nontumour-related chronic pain, have led to a revision of their use in neuropathic pain. Nevertheless, the use of opioid therapy for neurogenic pain remains controversial. Tramadol is a synthetic, centrally acting analgesic with both opioid and nonopioid analgesic activity. The nonopioid component is related to the inhibition of noradrenaline (norepinephrine) reuptake and stimulation of serotonin (5-hydroxytryptamine; 5-HT) release at the spinal level. In this regard, there are parallels with antidepressants, which are believed to potentiate the effect of biogenic amines in endogenous pain-relieving systems. There is evidence that, in tramadol, both mechanisms act synergistically with respect to analgesia. The aim of this pilot study was to investigate, for the first time, the analgesic efficacy and tolerability of tramadol, compared with the antidepressant clomipramine, in the treatment of postherpetic neuralgia. If necessary, clomipramine was used in combination with the neuroleptic levomepromazine. The study allowed individualised dosages at predetermined intervals up to a maximum daily dose of tramadol 600mg and clomipramine 100mg, or clomipramine 100mg with or without levomepromazine 100mg. 21 (60%) of 35 randomised patients (> or = 65 years) received the study medication over the 6-week period [tramadol n = 10; clomipramine with or without levomepromazine) n = 11]. After 3 weeks' treatment the dosage in both groups remained almost constant for the rest of the 6-week treatment phase (mean daily dose: tramadol 250 to 290mg; clomipramine 59.1 to 63.6mg). Only 3 patients required the combination of clomipramine and levomepromazine. At the outset, both groups recorded an average pain level of 'moderate' to 'very severe'. In correlation with increasing the study medication, this had decreased to 'slight' by the end of the treatment, when 9 of 10 patients in the tramadol group and of 6 of 11 patients in the clomipramine group retrospectively rated their analgesia as excellent, good or satisfactory. The psychological/physical condition of the patients did not change significantly during tramadol treatment. Sensitivity and depression parameters decreased in the clomipramine group. The incidence of adverse events for all patients was similar in both groups (tramadol 76.5%; clomipramine with or without levomepromazine 83.3%). In conclusion, tramadol would appear to be an interesting therapeutic alternative for pain relief in postherpetic neuralgia, particularly in patients who are not depressed. In clinical practice, tramadol and clomipramine can best be used differentially. For example, tramadol could be the drug of first choice in patients with obvious cardiovascular disease (not an uncommon problem in the > or = 65 year age group) in whom antidepressants are contraindicated, and similarly in patients in whom an antidepressant effect is not required. (ABSTRACT TRUNCATED)

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain.

Reports of gabapentin use in diabetic peripheral neuropathy pain stimulate a need for controlled trials to determine its comparative efficacy to the therapeutic standard of amitriptyline hydrochloride. To determine the efficacy of gabapentin compared with amitriptyline in treating diabetic peripheral neuropathy pain. Prospective, randomized, double-blind, double-dummy, crossover study. Veterans Affairs San Diego Healthcare System, Ambulatory Care Clinic. Twenty-eight veterans were referred by their primary care providers. Two patients withdrew before randomization because of no neuropathic pain after washout; a third withdrew for unexpected surgery that required analgesics. Three patients withdrew because of adverse effects and 1 for protocol violation. Patients with stable glycemic control and neuropathic pain randomized to 6 weeks of therapy with gabapentin, 900 to 1800 mg/d, or amitriptyline hydrochloride, 25 to 75 mg/d, with a 1-week washout before crossover. Pain relief measured by pain scale with verbal descriptors and global pain score assessment at treatment end. Participants and investigators were blinded throughout. Mean dosages were of gabapentin, 1565 mg/d, and of amitriptyline hydrochloride, 59 mg/d. Sixty-five percent of patients reached maximum dose with gabapentin and 54% with amitriptyline. Mean score diary analysis showed pain relief with gabapentin and amitriptyline was not significantly different (P = .26). Global data were obtained from 21 of 25 enrolled patients who completed the study. Moderate or greater pain relief was experienced in 11 (52%) of 21 patients with gabapentin and 14 (67%) of 21 patients with amitriptyline. There were no significant period or carry-over effects (P = .35). Although both drugs provide pain relief, mean pain score and global pain score data indicate no significant difference between gabapentin and amitriptyline. Gabapentin may be an alternative for treating diabetic peripheral neuropathy pain, yet does not appear to offer considerable advantage over amitriptyline and is more expensive. Larger trials are necessary to define gabapentin's place in treating diabetic peripheral neuropathy pain.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Antidepressants for cancer pain and other painful syndromes with deafferentation component: comparison of amitriptyline and trazodone.

The Authors report a clinical multicentre experience with antidepressant agents (trazodone and amitriptyline) in the treatment of chronic cancer pain with deafferentation component. Forty-five patients were admitted to the study: 27 with oncological peripheral nerve lesions, 6 with post herpetic neuralgias, 10 with not oncological nerve lesions, 2 with central nervous lesions. Almost all of them were already being treated with NSAID associated with weak or strong opioids. A random double blind study was performed: 23 patients were treated with trazodone, 22 with amitriptyline. In the assessment of results, pain intensity, hours of sleep, hours standing and lying, side effects, mood, anxiety, weakness were all taken into consideration. The therapeutic analgesic efficacy of the two drugs proved to be similar.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Evaluation of efficacy of the perioperative administration of venlafaxine XR in the prevention of postmastectomy pain syndrome.

Postmastectomy pain syndrome (PMPS) is a neuropathic pain syndrome that may develop following breast surgery. Venlafaxine has been shown to be efficacious in the management of PMPS. The preemptive administration of venlafaxine has been shown to be efficacious in reducing the incidence of neuropathic pain in the rat model. We examined the efficacy of administering either venlafaxine or placebo for two weeks starting the night before surgery to 100 patients scheduled for either partial or radical mastectomy with axillary dissection. Patients were administered PCA morphine for the first 24 hours following surgery and then acetaminophen/oxycodone tablets. Pain scores were recorded at rest and movement on day 1, at 1 month, and at 6 months after surgery. At 6 months postoperatively, the presence of pain in the chest, arm, and axilla; edema; decreased sensation in the operative area; and phantom breast pain were recorded. There was no difference in postoperative opioid use. Pain scores with movement were lower in the venlafaxine group at 6 months. Pain scores at all other time intervals were similar. There was a significant decrease in the incidence of chest wall pain (55% vs. 19%, P = 0.0002), arm pain (45% vs. 17%, P = 0.003), and axilla pain (51% vs. 19%, P = 0.0009) between the control group and the venlafaxine group, respectively. No significant differences were noted between the two groups with regard to edema, phantom pain, or sensory changes. We conclude that the perioperative administration of venlafaxine beginning the night prior to surgery significantly reduces the incidence of PMPS following breast cancer surgery.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Psychogenic facial pain: presentation and treatment.

Ninety three patients took part in a two centre double blind controlled clinical trial designed to assess the efficacy of dothiepin (Prothiaden) as compared with placebo and a soft biteguard in the treatment of psychogenic facial pain. The results showed the superiority of dothiepin over placebo in achieving pain relief; 71% of patients were pain free in the dothiepin group at nine weeks compared with 47% in the placebo group. The biteguard conferred no benefit and compliance in its use was poor. Out of 84 patients followed up for 12 months, 68 (81%) became pain free. An adverse life event before development of pain, minimal previous surgical treatment, and freedom from pain at nine weeks were strong prognostic indicators for successful treatment. These results are clear evidence of the efficacy of dothiepin in psychogenic facial pain, though the drug may be needed for up to a year.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study.

To evaluate the efficacy and safety of 6 weeks of venlafaxine extended-release (ER) (75 mg and 150-225 mg) treatment in patients with painful diabetic neuropathy. This multicenter, double-blind, randomized, placebo-controlled study included 244 adult outpatients with metabolically stable type 1 or 2 diabetes with painful diabetic neuropathy. Primary efficacy measures were scores on the daily 100 mm Visual Analog Pain Intensity (VAS-PI) and Pain Relief (VAS-PR) scales. Secondary efficacy measures included the Clinical Global Impressions-Severity of Illness and the Clinical Global Impressions-Improvement, Patient Global Rating of Pain Relief, and percentage of patients achieving 50% reduction in pain intensity. Baseline pain intensity was 68.7 mm (moderately severe). At week 6, the percentage reduction from baseline in VAS-PI was 27% (placebo), 32% (75 mg), and 50% (150-225 mg; P < 0.001 vs placebo). Mean VAS-PR scores in the 150-225 mg group were significantly greater than placebo at week 6 (44 vs 60 mm; P < 0.001). The number needed to treat (NNT) for 50% pain intensity reduction with venlafaxine ER 150-225 mg was 4.5 at week 6. Nausea and somnolence were the most common treatment-emergent adverse events. Seven patients on venlafaxine had clinically important ECG changes during treatment. Venlafaxine ER appears effective and safe in relieving pain associated with diabetic neuropathy. NNT values for higher dose venlafaxine ER are comparable to those of tricyclic antidepressants and the anticonvulsant gabapentin.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

A double-blind comparison of topical capsaicin and oral amitriptyline in painful diabetic neuropathy.

An 8-week double-blind, multicenter, parallel study compared the safety and efficacy of topical capsaicin and oral amitriptyline in patients with painful diabetic neuropathy involving the feet. Two hundred thirty-five patients were randomized to treatment with either capsaicin cream or amitriptyline capsules. Capsaicin-treated patients received inactive capsules, and amitriptyline-treated patients applied vehicle cream. A visual analogue scale of pain intensity and measurements of interference by pain with functional activities were recorded at onset and at 2-week intervals. A visual analogue scale of pain relief and physicians' global evaluation assessed changes in pain status from baseline. Topical capsaicin and oral amitriptyline produced equal and statistically significant improvements in pain over the course of the study. By the end of week 8, 76% of patients in each group experienced less pain, with a mean reduction in intensity of more than 40%. By the end of the study, the interference with daily activities by pain had diminished significantly (P = .001) in both groups, including improvements in sleeping and walking. No systemic side effects were observed in patients treated with topical capsaicin. Most patients receiving amitriptyline experienced at least one systemic side effect, ranging from somnolence (46%) to neuromuscular (23%) and cardiovascular (9%) adverse effects. Topically applied capsaicin is an equally effective but considerably safer alternative to amitriptyline for relief of the pain of diabetic neuropathy.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Imipramine treatment in diabetic neuropathy: relief of subjective symptoms without changes in peripheral and autonomic nerve function.

The effect of imipramine on symptomatic peripheral diabetic neuropathy in 9 patients was examined in a double-blind cross-over study against placebo. The dose of imipramine was adjusted to yield optimal plasma levels of imipramine plus desipramine of 300-750 nM. Imipramine had a clear beneificial effect on the symptoms of the neuropathy, whereas no changes in a range of neurophysiological measurement was detected. Despite some adverse effects, especially of an anticholinergic nature, the patients generally preferred imipramine to placebo.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain.

To evaluate the effectiveness and safety of bupropion sustained-release (SR) for the treatment of neuropathic pain. This single-center, outpatient, randomized, double-blind, placebo-controlled, crossover study consisted of two phases. Forty-one nondepressed patients with neuropathic pain spent 6 weeks in each phase in random order and received identical tablets of 150 mg bupropion SR or placebo. Patients were instructed to take one tablet once daily for 1 week followed by one tablet twice daily for 5 weeks. While the patients took bupropion SR, neuropathic pain relief was improved or much improved in 30 (73%) patients, and one of these patients became pain-free. The mean average pain score at baseline was 5.7, which remained unchanged at the end of week 6 with placebo, but decreased by 1.7 points to 4.0 (p < 0.001) during therapy with bupropion SR. Pain relief with bupropion SR was significant at week 2 (p < 0.05) and continued throughout weeks 3 through 6 (p < 0.001). A significant decrease in interference of pain on quality of life was observed while patients were receiving bupropion SR compared with placebo. Side effects experienced with bupropion SR were not dose-limiting and consisted primarily of dry mouth, insomnia, headache, gastrointestinal upset, tremor, constipation, and dizziness. This placebo-controlled crossover trial showed that bupropion SR (150-300 mg daily) was effective and well tolerated for the treatment of neuropathic pain.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms.

The effect of the selective serotonin reuptake inhibitor paroxetine on diabetic neuropathy symptoms was examined in comparison to imipramine and placebo in a randomised, double-blind, cross-over study. Paroxetine was given as a fixed dose of 40 mg/day, while the dose of imipramine was adjusted to yield optimal plasma levels of imipramine plus desipramine of 400-600 nM. Paroxetine significantly reduced the symptoms of neuropathy as measured by both observer- and self-rating, but was somewhat less effective than imipramine. However, patients showing a weaker response to paroxetine than to imipramine had lower plasma concentrations of paroxetine than patients with similar response to the 2 drugs. On imipramine 5 patients dropped out because of intolerable side effects and 4 of 19 patients completing the study reported withdrawal symptoms after discontinuing imipramine. On paroxetine no patients dropped out due to side effects and no withdrawal symptoms were reported. Self-rating showed no depressive symptoms at baseline, and no changes during the study. Neither paroxetine nor imipramine caused changes in objective measures of peripheral nerve function. In conclusion, 40 mg paroxetine/day significantly reduced the symptoms in peripheral diabetic neuropathy, and it was suggested that by dose adjustment on the basis of drug level monitoring, paroxetine may become as effective as imipramine. Paroxetine was devoid of the often disturbing autonomic side effects limiting the use of imipramine in several patients.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

A controlled study of amitriptyline in the treatment of chronic pain.

This paper reports a study in which a double-blind controlled cross-over study of amitriptyline vs. placebo was carried out in a group of patients referred to a multidisciplinary pain clinic for the management of chronic intractable pain for which no substantial organic cause could be demonstrated. Of 52 patients entering the 12-week trial, 20 withdrew before completion. No differences were found in terms of global improvement on either agent. Subjective reports indicated a greater reduction in pain at 2 and 4 weeks on amitriptyline, but no difference at 6 weeks. None of the baseline measures was predictive of response.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain.

Antidepressant drugs are increasingly used in the management of chronic pain. They are mainly prescribed for cancer-related pain and central pain, e.g. phantom or stump pain, post-herpetic neuropathy. However, no controlled clinical trials have validated their in either pathology. Thus, physicians still do not know whether antidepressants are really effective and which might be best. It is still debated whether the effect of antidepressants in the management of chronic pain is limited to the amelioration of frequently concomitant depression or extends to pain itself. To verify both the analgesic effect of tricyclic antidepressants, and the possible relationship between their antidepressant effect and the relief of central pain, we carried out a randomized, within-patient (cross-over) placebo-controlled study in patients suffering from central pain. The results clearly indicate the better analgesic effect of tricyclic antidepressants over placebo (p less than 0.0001). Within the antidepressants tested, chlorimipramine, a blocker of serotonin reuptake, is significantly more effective (p less than 0.0001) than notriptyline, a blocker of noradrenaline reuptake. Finally, the antinociceptive effect is independent of the effects of the two drugs on the symptoms of depression.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial.

Tricyclic antidepressants (TCA) provide less than satisfactory pain relief for postherpetic neuralgia (PHN), and the role of opioids is controversial. To compare the analgesic and cognitive effects of opioids with those of TCA and placebo in the treatment of PHN. Seventy-six patients with PHN were randomized in a double-blind, placebo-controlled, crossover trial. Each subject was scheduled to undergo three treatment periods (opioid, TCA, and placebo), approximately 8 weeks' duration each. Doses were titrated to maximal relief or intolerable side effects. The primary outcome measures were pain intensity (0 to 10 scale), pain relief (0 to 100%), and cognitive function. Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication. Fifty patients completed two periods, and 44 patients completed all three. Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg. Opioids and TCA reduced pain (1.9 and 1.4) more than placebo (0.2; p < 0.001), with no appreciable effect on any cognitive measure. The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%; p < 0.001). More patients completing all three treatments preferred opioids (54%) than TCA (30%; p = 0.02). Opioids effectively treat PHN without impairing cognition. Opioids and TCA act via independent mechanisms and with varied individual effect.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Trial of amitriptyline for relief of pain in amputees: results of a randomized controlled study.

To evaluate whether amitriptyline is more effective than placebo in improving phantom limb pain or residual limb pain. Randomized controlled trial of amitriptyline for 6 weeks. University hospital. Thirty-nine persons with amputation-related pain lasting more than 6 months. Six-week trial of amitriptyline (titrated up to 125 mg/d) or an active placebo (benztropine mesylate). Analyses were conducted to examine whether there was a medication group effect on the primary outcomes (average pain intensity) and secondary outcome measures (disability, satisfaction with life, handicap). No significant differences were found between the treatment groups in outcome variables when controlling for initial pain scores. Our findings do not support the use of amitriptyline in the treatment of postamputation pain.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Desipramine relieves postherpetic neuralgia.

Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressant agents, but its pain-relieving potential has received little study. Other antidepressant agents--notably amitriptyline--are known to ameliorate postherpetic neuralgia, but those agents are often toxic. In a randomized double-blind crossover design, we gave 26 postherpetic neuralgia patients 6 weeks of treatment with desipramine (mean dose, 167 mg/day) and placebo. Nineteen patients completed both treatments; 12 reported at least moderate relief with desipramine and two reported relief with placebo. Pain relief with desipramine was statistically significant from weeks 3 to 6. Psychiatric interview at entry into the study produced a diagnosis of depression for 4 patients; pain relief was similar in depressed and nondepressed patients and was statistically significant in the nondepressed group alone. We conclude that desipramine administration relieves postherpetic neuralgia and that pain relief is not mediated by mood elevation. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressant agents that have relieved neuropathic pain, may be involved in relief of postherpetic neuralgia.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study.

To assess the analgesic efficacy of topical administration of 3.3% doxepin hydrochloride, 0.025% capsaicin and a combination of 3. 3% doxepin and 0.025% capsaicin in human chronic neuropathic pain. A randomized, double-blind, placebo-controlled study of 200 consenting adult patients. Patients applied placebo, doxepin, capsaicin or doxepin/capsaicin cream daily for 4 weeks. Patients recorded on a daily basis overall pain, shooting, burning, paraesthesia and numbness using a 0-10 visual analogue scale during the week prior to cream application (baseline levels) and for the 4 week study period. Side-effects and desire to continue treatment were also recorded. Overall pain was significantly reduced by doxepin, capsaicin and doxepin/capsaicin to a similar extent. The analgesia with doxepin/capsaicin was of more rapid onset. Capsaicin significantly reduced sensitivity and shooting pain. Burning pain was increased by doxepin and by capsaicin and to a lesser extent by doxepin/capsaicin. Side-effects were minor. One patient requested to continue placebo cream, 17 doxepin cream, 13 capsaicin and 9 the combination of doxepin and capsaicin. Topical application of 3.3% doxepin, 0.025% capsaicin and 3.3% doxepin/0. 025% capsaicin produces analgesia of similar magnitude. The combination produces more rapid analgesia.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

An open and double-blind cross-over study on the efficacy of clomipramine (Anafranil) in patients with painful mono- and polyneuropathies.

82 patients with chronic pain resulting from mononeuropathy were treated with psychotropic drugs in an open therapeutic study. In this study we found that treatment with a combination of clomipramine (Anafranil) and small doses of neuroleptics was significantly superior to therapy with neuroleptics alone. In a subsequent double-blind study, it was attempted for the first time to determine the efficacy of clomipramine compared to that of acetylsalicylic acid in 48 patients with painful mono- and polyneuropathies. The test was carried out in a cross-over trial with two sequence groups. We evaluated assessments of pain by both patients and doctors, and were able to prove statistically that clomipramine possesses a significantly greater efficacy compared to that of acetylsalicylic acid. By taking into account recent anatomical, biochemical and pharmacological studies, it can be concluded that clomipramine probably has-in addition to the action on peripheral receptors-a direct effect upon pain modulation systems. It seems possible that clomipramine activates serotonin-containing neurons of the endorphin-mediated analgesia system that control pain transmission in the CNS.

CD005454

This update has provided additional confirmation on the effectiveness of antidepressants for neuropathic pain and has provided new information on another antidepressant - venlafaxine. There is still limited evidence for the role of SSRIs. Whether antidepressants prevent the development of neuropathic pain (pre-emptive use) is still unclear. Both TCAs and venlafaxine have NNTs of approximately three. This means that for approximately every three patients with neuropathic pain who are treated with either of these antidepressants, one will get at least moderate pain relief. There is evidence to suggest that other antidepressants may be effective but numbers of participants are insufficient to calculate robust NNTs. SSRIs are generally better tolerated by patients and more high quality studies are required.

Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial.

Although amitriptyline relieves pain in many patients with painful diabetic neuropathy, side effects often preclude effective treatment. Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressants. We compared a 6 week course of desipramine (mean dose, 201 mg/day) to active placebo in 20 patients with painful diabetic neuropathy in a double-blind crossover trial. Pain relief with desipramine was statistically significant in weeks 5 and 6. Eleven patients reported at least moderate relief with desipramine, compared to 2 with placebo. Pain relief tended to be greater in depressed patients, but relief was also observed in patients who did not show an antidepressant effect. We conclude that desipramine relieves pain in many patients with painful diabetic neuropathy, offering an alternative for patients unable to tolerate amitriptyline. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressants proven effective in neuropathic pain, may mediate this analgesic effect.

CD004897

Preliminary studies suggest benefit from blood alkalinisation with NaHCO3 in OP poisoning, but there is insufficient evidence to support its routine clinical use. Further research is required to determine the method of alkalinisation that will optimise outcomes, and the regimen which will produce the target arterial pH of 7.50 (range 7.45 to 7.55). This should be followed by a well-designed randomised controlled trial to determine efficacy.

Effect of high doses of sodium bicarbonate in acute organophosphorous pesticide poisoning.

The sodium bicarbonate (NaHCO3) dosage used in treating the patients with organophosphorous pesticide (OP) poisoning did not result in sufficient alkalinization of the blood. We thus investigated the effects of higher doses by infusion (5 mEq/kg over 1 hour, followed by 5-6 mEq/kg daily until recovery or death) to maintain the arterial pH between 7.45 and 7.55. There were 26 (14 M and 12 F) patients aged 24.1 +/- 9.7 years and 27 (16 M and 11 F) aged 25.7 +/- 9.1 years in the test and contro groups, respectively. Arterial blood pH of the test group (7.48 +/- 0.02) was much higher (p < 0.0001) than the controls (7.36 +/- 0.02). The total atropine doses used for the control patients (129.45 +/- 61 mg) was significantly (p = 0.048) higher than the controls (93.4 +/- 59.1 mg). Hospitalization days were statistically higher (p = 0.037) in the controls (5.59 +/- 1.97 days) than in the bicarbonate group (4.33 +/- 1.99 days). Infusion of high doses of NaHCO3 appears to be beneficial in treatment of patients with OP poisoning.

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

Experimental comparison of the effectivity of individually adapted and standardized dosages of haloperidol.

Experimental tests of whether an individual neuroleptic treatment for compensation of acute schizophrenic disorders is more effective and has fewer side effects than a standard therapy were performed under double-blind conditions. For this purpose, a group of 16 patients was treated with 10 mg haloperidol/day for the duration of 14 days, and another group of 16 patients was treated with 20 mg haloperidol/day for the same period. 16 patients of a third group were treated for 14 days with an individual haloperidol dose adapted to the psychopathological findings. Patients were randomly allocated to the treatment groups. The medication was laid down in accordance with the randomization plan without informing the ward staff and raters by a leading physician of the hospital who was not involved in the data collection in the investigation. The psychological findings were registered by means of the BPRS and the global appraisal by the doctor (CGI) on days 0, 7 and 14. Extrapyramidal side effects were registered by means of the Simpson scale on days 0, 7 and 14. A superiority of the individually adapted treatment over standardized treatment could be demonstrated neither for the therapeutic target parameters nor for the side effect variables. On the contrary, a tendency to superiority in the groups treated with fixed doses was found. The results are discussed in terms of their significance for treatment practice.

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

Haloperidol for acute schizophrenic patients. An evaluation of three oral regimens.

The relative efficacy of three oral regimens of haloperidol was compared in a ten-day, double-blind study of 63 acutely ill schizophrenic patients newly admitted to the hospital. One group of patients received 20 mg of haloperidol on day 1, then increasing increments of 20 mg a day, reaching a maximum dosage of 100 mg daily on day 5. Another group received 10 mg of haloperidol on day 1, then increasing increments of 10 mg daily, reaching 100 mg daily on day 10. A third group of patients received a fixed dosage of 10 mg daily for ten days. Haloperidol was well tolerated by the patients; there were no serious adverse reactions. The data indicated that the regimens had similar therapeutic efficacy, suggesting that acutely ill schizophrenic patients respond to a wide range of doses of haloperidol but that onset of response and efficacy are not increased in most patients by providing a high initial loading dosage. Adequate, safe dosage must be determined in each case.

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

Effects of high and low dosage of haloperidol on the brain in relation to schizophrenic thought disorder.

The drug difference between a low and a high dosage of haloperidol was investigated in 40 acutely ill schizophrenic patients. All patients were classified as being thought disordered or non-thought disordered schizophrenic using psychometric methods. From the pool of 40 patients two groups were randomly chosen for the double-blind study, one group receiving 80 mg of liquid haloperidol daily, the other group 16 mg of liquid haloperidol daily. On 5 days during the 21-day treatment the psychopathological state of the patient was evaluated by means of the AMDP system.

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

Optimal dose of neuroleptic in acute schizophrenia. A controlled study of the neuroleptic threshold and higher haloperidol dose.

After individual determination of neuroleptic threshold (NT) doses of haloperidol, 106 patients with schizophrenia or schizoaffective disorder (Research Diagnostic Criteria) were treated openly at such doses (mean, 3.7 +/- 2.3 mg/d) for 2 weeks. Ten responding patients were discharged and unavailable for follow-up or refused subsequent randomization, and one non-responding patient refused randomization. The remaining 95 responding or nonresponding patients were then randomly assigned, double-blind, to a dosage of haloperidol two to 10 times higher (mean, 11.6 +/- 4.7 mg/d) or to a continuing NT dosage (mean, 3.4 +/- 2.3 mg/d) for another 2 weeks. Of the 58 patients exposed only to NT dosages of haloperidol, 72% clinically recovered within the 5-week trial. Higher dosages given to 47 patients did not lead to greater improvement in measures of psychosis, but did produce slightly greater declines in measures of hostility. Higher dosages did regularly lead to significant increases in distressing extrapyramidal side effects.

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

Dosage of haloperidol for schizophrenia.

Eighty-seven newly admitted inpatients with schizophrenia were randomized to receive 10, 30, or 80 mg/d of oral haloperidol. They were treated under double-blind conditions for 6 weeks, less if their acute symptoms remitted sooner. Survival analysis showed no differences among the three treatments. Side effects were minimal in all three treatment groups, and there were no differences in side effects among the groups. These results suggest that dosages higher than 10 mg/d of haloperidol for most patients have no additional beneficial effect in the treatment of acute or exacerbated schizophrenia.

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

Haloperidol plasma level after a test dose as predictor for the clinical response to treatment in acute schizophrenic patients.

In a fixed-dose, double-blind study, the clinical response of schizophrenic patients to a high (0.40 mg/kg) or a low (0.15 mg/kg) dose of haloperidol (HL) was compared. The relationship between HL steady-state plasma levels and clinical improvement was examined. The utility of HL plasma level after a single test dose (0.05 mg/kg) in predicting the clinical response to treatment was evaluated. No difference in clinical improvement was observed between the two groups as a whole, although the high-dose group had a faster initial improvement. The high-dose group showed more extrapyramidal effects during treatment. No relationship was found between HL steady-state levels and clinical improvement. For the low-dose group, HL plasma level after the test dose was significantly positively correlated with the improvement after eight days of treatment. The test dose HL plasma level was no predictor of the clinical response to treatment in the high-dose group. The possibility of predicting the clinical response of schizophrenic patients to treatment from the plasma level after a test dose is still an open question that requires further studies.

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

Further evidence of a dose-response threshold for haloperidol in psychosis.

The authors' goal was to determine whether higher doses of haloperidol improve antipsychotic response. During a 2-week, double-blind, randomized fixed-dose study, 24 psychotic patients were given 4, 10, or 40 mg/day of haloperidol. No clinically relevant difference between groups in favor of the higher antipsychotic doses could be detected. Doses of 4 mg/day of haloperidol appear to be as effective as higher doses in the treatment of psychosis.

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

A two-phase, double-blind randomized study of three haloperidol plasma levels for acute psychosis with reassignment of initial non-responders.

To clarify the plasma level/therapeutic response relationship of haloperidol (HPDL) we used a prospective double-blind design in 95 acutely psychotic patients. After drug washout, patients were randomly assigned to a low, middle or high plasma level range for 2 weeks (phase A), and then 50% of the initial non-responders were randomly reassigned into the putative therapeutic range for an additional 2 weeks (phase B). There were no significant differences in clinical outcome between the three plasma level ranges in phase A. However, in phase B initial non-responders displayed greater improvement in the middle range than in the low or the high ranges. No further benefit was observed when plasma levels were raised to or maintained in the high range.

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

[Comparison of the therapeutic effects between haloperidol and insulin coma in schizophrenia and optimal blood levels of haloperidol].

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia.

Since all antipsychotics block dopamine D(2) receptors, the authors investigated how well D(2) receptor occupancy in vivo predicts clinical response, extrapyramidal side effects, and hyperprolactinemia. In a double-blind study, 22 patients with first-episode schizophrenia were randomly assigned to 1.0 or 2. 5 mg/day of haloperidol. After 2 weeks of treatment, D(2) receptor occupancy was determined with [(11)C]raclopride and positron emission tomography, and clinical response, extrapyramidal side effects, and prolactin levels were measured. Patients who showed adequate responses continued taking their initial doses, those who did not respond had their doses increased to 5.0 mg/day, and evaluations were repeated at 4 weeks for all patients. The patients showed a wide range of D(2) occupancy (38%-87%). The degree of receptor occupancy predicted clinical improvement, hyperprolactinemia, and extrapyramidal side effects. The likelihood of clinical response, hyperprolactinemia, and extrapyramidal side effects increased significantly as D(2) occupancy exceeded 65%, 72%, and 78%, respectively. The study confirms that D(2) occupancy is an important mediator of response and side effects in antipsychotic treatment. The data are consistent with a "target and trigger" hypothesis of antipsychotic action, i.e., that the D(2) receptor specificity of antipsychotics permits them to target discrete neurons and that their antagonist properties trigger within those neurons intracellular changes that ultimately beget antipsychotic response. While limited to haloperidol, the relationship between D(2) occupancy and side effects in this study helps explain many of the observed clinical differences between typical and atypical antipsychotics.

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

Haloperidol: therapeutic window in schizophrenia.

Twenty-two schizophrenic inpatients were treated for 3 weeks with three randomly fixed oral doses of haloperidol (10, 20, or 30 mg). Analysis of the results by a nonlinear regression model revealed a curvilinear relationship between haloperidol levels in plasma and clinical response, as assessed on the Brief Psychiatric Rating Scale (pseudo-R2 = 0.85, F = 17.7, p < 0.001, correlation between coefficients ranged from 0.99 to -0.52). This curve defines roughly three drug level ranges (low, < 5.5 ng/ml; optimal, 5.5 to 14.4 ng/ml; and high or toxic, > 14.4 ng/ml), which are significant for clinical practice. Patients with high levels improve to a lesser extent or even worsen in negative symptoms, showing a nonstatistically significant trend to present more extrapyramidal symptoms. Our data thus support the existence of a therapeutic window for haloperidol. Schizophrenic patients with acute exacerbation and drug levels in this range would have a greater probability of global clinical improvement.

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

Rapid treatment of acute psychotic symptoms with high- and low-dose haloperidol. Behavioral considerations.

Twenty acutely psychotic male psychiatric inpatients were assigned to two groups and treated with high- and low-dose haloperidol using a rapid neuroleptization technique. A six-day maintenance phase followed. Both groups improved at one hour, one day, and seven days after starting treatment, and neither group differed as to degree or rapidity of symptom alleviation. Therefore, the results of the study do not give experimental support for the administration of high doses of haloperidol to young, acutely psychotic inpatients with relatively good prognoses.

CD001951

No results are conclusive and all are based on small, short, studies. It would be understandable, however, if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the >1.5-3.0 mg/day dose range.

Plasma haloperidol levels and clinical effects in schizophrenia and schizoaffective disorder.

Plasma haloperidol levels between 5 and 11 ng/mL may be clinically optimal for acutely exacerbated schizophrenia, but the evidence for this therapeutic window has been inconsistent. Haloperidol was administered in a double-blind manner during two consecutive 3-week experimental periods to 65 patients with acutely exacerbated schizophrenia or schizoaffective disorder. Two plasma levels were targeted: "low" (2 ng/mL) and "moderate" (10 ng/mL). The subjects were randomly assigned to four treatment sequences (low-low, low-moderate, moderate-moderate, or moderate-low). In the first 3 weeks, the antipsychotic efficacy of haloperidol increased with plasma levels up to approximately 12 ng/mL. In the second 3 weeks, decrease of plasma levels reduced negative symptoms. For most patients, plasma levels not exceeding 12 ng/mL yield the best results in the first 3 weeks of treatment. Subsequent lowering of the plasma levels may improve negative symptoms.

CD006989

In view of the lack of evidence for the benefit or lack of benefit of antihistamine add-on therapy with topical nasal steroids for children with intermittent or persistent allergic rhinitis, it is important that clinicians are mindful of the adverse effects of antihistamines and the additional costs that may be incurred.

Is the usage of intranasal glucocorticosteroids alone in allergic rhinitis sufficient?

Recently, it is claimed that the usage of the intranasal glucocorticosteroids alone, instead of H1-antihistamines + intranasal glucocorticosteroids, reduces the complaints in moderate-to-severe seasonal allergic rhinitis (SAR). This study aims to evaluate the efficacy of the intranasal glucocorticosteroids alone during the pollen season by using objective and subjective parameters. Twenty-four patients (mean age, 12.17 +/- 2.26 years) with SAR sensitive to pollen are included in this study. The patients were divided into two groups randomly. Twelve patients in group I were given H1-antihistamine (loratadine) + intranasal glucocorticosteroid (mometasone furoate), and 12 patients in group II were given only intranasal glucocorticosteroid (mometasone furoate) for 12 weeks. To evaluate the results, subjective parameters (daytime nasal symptoms score, daytime eye symptoms score, and nighttime symptoms score) and objective parameters (nasal smear, nasal peak inspiratory flow [NPIF], and nasal biopsy) are used. With regard to the baseline data, it was observed that both groups had a significant decrease in total symptom score (p < 0.01), a significant increase in NPIF values (p < 0.01), and a significant decrease in the number of eosinophils in both nasal smear and biopsy (p < 0.01) after treatment. Comparing groups I and II in terms of treatment success, the improvement in daytime nasal symptoms score (p < 0.01 versus p < 0.01), daytime eye symptoms score (p < 0.01 versus p < 0.01), and total symptom score (p < 0.versus p < 0.01) was not different. However, there was a significant improvement in nighttime symptoms score between groups I and II (p < 0.01 versus p > 0.05). Furthermore, NPIF and nasal biopsy findings did not differ between groups (p > 0.05). The usage of H1-antihistamine + intranasal glucocorticosteroid has no superiority over the administration of intranasal glucocorticosteroid alone for treatment of SAR in pollen season. However, this finding needs to be confirmed in larger series studies.

CD002744

Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.

Zanamivir prophylaxis: an effective strategy for the prevention of influenza types A and B within households.

A double-blind, randomized study of inhaled zanamivir for the prevention of influenza in families was conducted. Once a person with a suspected case of influenza was identified (index patient), treatment of all other household members (contacts) > or =5 years old was initiated. Contacts received either 10 mg zanamivir or placebo inhaled once daily for 10 days. Index patients received relief medication only. In total, 487 households (242 placebo and 245 zanamivir) were enrolled, with 1291 contacts randomly assigned to receive prophylaxis. Four percent of zanamivir versus 19% of placebo households (P<.001) had at least 1 contact who developed symptomatic, laboratory-confirmed influenza, representing 81% protective efficacy (95% confidence interval, 64%-90%). Protective efficacy was similarly high for individuals (82%) and against both influenza types A and B (78% and 85%, respectively, for households). Zanamivir was well tolerated and was effective in preventing influenza types A and B within households where the index patient was not treated.

CD002744

Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.

Long-acting neuraminidase inhibitor laninamivir octanoate (CS-8958) versus oseltamivir as treatment for children with influenza virus infection.

We conducted a double-blind, randomized controlled trial to compare a long-acting neuraminidase inhibitor, laninamivir octanoate, with oseltamivir. Eligible patients were children 9 years of age and under who had febrile influenza symptoms of no more than 36-h duration. Patients were randomized to 1 of 3 treatment groups: a group given 40 mg laninamivir (40-mg group), a group given 20 mg laninamivir (20-mg group), and an oseltamivir group. Laninamivir octanoate was administered as a single inhalation. Oseltamivir (2 mg/kg of body weight) was administered orally twice daily for 5 days. The primary end point was the time to alleviation of influenza illness. The primary analysis included 184 patients (61, 61, and 62 in the 40-mg group, 20-mg group, and oseltamivir group, respectively). Laninamivir octanoate markedly reduced the median time to illness alleviation in comparison with oseltamivir in patients infected with oseltamivir-resistant influenza A (H1N1) virus, and the reductions were 60.9 h for the 40-mg group and 66.2 h for the 20-mg group. On the other hand, there were no significant differences in the times to alleviation of illness between the laninamivir groups and oseltamivir group for patients with influenza A (H3N2) or B virus infection. Laninamivir octanoate was well tolerated. The most common adverse events were gastrointestinal events. Laninamivir octanoate was an effective and well-tolerated treatment for children with oseltamivir-resistant influenza A (H1N1) virus infection. Further study will be needed to confirm clinical efficacy against influenza A (H3N2) or B virus infection. Its ease of administration is noteworthy, because a single inhalation is required during the course of illness.

CD002744

Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.

Early oseltamivir treatment of influenza in children 1-3 years of age: a randomized controlled trial.

Oseltamivir provides modest clinical benefits to children with influenza when started within 48 hours of symptom onset. The effectiveness of oseltamivir could be substantially greater if the treatment were started earlier during the course of the illness. We carried out a randomized, double-blind, placebo-controlled trial of the efficacy of oseltamivir started within 24 hours of symptom onset in children 1-3 years of age with laboratory-confirmed influenza during the seasons of 2007-2008 and 2008-2009. Eligible children received either orally administered oseltamivir suspension or a matching placebo twice daily for 5 days. The children received clinical examinations, and the parents filled out detailed symptom diaries for 21 days. Of 408 randomized children who received the study drug (oseltamivir, 203, and placebo, 205), 98 had laboratory-confirmed influenza (influenza A, 79, and influenza B, 19). When started within 12 hours of the onset of symptoms, oseltamivir decreased the incidence of acute otitis media by 85% (95% confidence interval, 25%-97%), but no significant reduction was observed with treatment started within 24 hours. Among children with influenza A, oseltamivir treatment started within 24 hours shortened the median time to resolution of illness by 3.5 days (3.0 vs 6.5 days; P = .006) in all children and by 4.0 days (3.4 vs 7.3; P = .006) in unvaccinated children and reduced parental work absenteeism by 3.0 days. No efficacy was demonstrated against influenza B infections. Oseltamivir treatment started within 24 hours of symptom onset provides substantial benefits to children with influenza A infection. Clinical trials registration. ClinicalTrials.gov identifier: NCT00593502.

CD002744

Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.

Zanamivir for treatment of symptomatic influenza A and B infection in children five to twelve years of age: a randomized controlled trial.

Influenza infection rates are higher in children than in other age groups. This study evaluated the efficacy, safety and tolerability of a 5-day course of twice daily inhaled zanamivir, 10 mg, compared with placebo in the treatment of symptomatic influenza A and B viral infections among children 5 to 12 years of age. This double blind, randomized, placebo-controlled, parallel group, multicenter study conducted in the Northern Hemisphere during the 1998 and 1999 influenza season enrolled 471 patients with influenza-like symptoms for < or = 36 h. Patients were randomly assigned to zanamivir (n = 224) or placebo (n = 247). Symptoms were recorded on diary cards twice daily during treatment, for 9 days after treatment and for 14 additional days (if still reporting moderate/severe cough and/or taking relief medication). A total of 346 (73%) patients were influenza-positive by culture, serology or polymerase chain reaction (65% influenza A, 35% influenza B). Zanamivir reduced the median time to symptom alleviation by 1.25 days compared with placebo among patients with confirmed influenza infection (P < 0.001). Zanamivir-treated patients returned to normal activities significantly faster and took significantly fewer relief medications than placebo-treated patients. Zanamivir was well-tolerated, demonstrating adverse event profiles similar to those of placebo and no clinically significant changes in laboratory findings. Viral susceptibility testing revealed no zanamivir-resistant strains of influenza A or B. Zanamivir was effective in shortening the duration and severity of influenza symptoms and was well-tolerated among children 5 to 12 years of age.

CD002744

Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.

Management of influenza in households: a prospective, randomized comparison of oseltamivir treatment with or without postexposure prophylaxis.

We determined the efficacy of postexposure prophylaxis (PEP) and treatment of ill index cases with oseltamivir, in an attempt to prevent influenza transmission in households, in a study conducted in 277 households with 298 index cases (62% with laboratory-confirmed influenza) and 812 contacts aged > or =1 year. Contacts were randomized by household to receive treatment (5 days; n=402), if illness developed, or PEP for 10 days (n=410), and the number of households with at least 1 contact developing laboratory-confirmed influenza was measured. PEP provided a protective efficacy of 58.5% (95% confidence interval [CI], 15.6%-79.6%; P=.0114) for households against proven influenza and 68.0% (95% CI, 34.9%-84.2%; P=.0017) for individual contacts, compared with treatment of index cases alone. No oseltamivir-resistant variants were detected in treated index cases or contacts. PEP of household contacts of those with influenza reduces the secondary spread of influenza in families when the initial household case is treated.

CD002744

Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.

Oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenza-infected children with asthma.

Among asthmatic children, influenza is associated with increased hospitalizations. Although vaccination is safe and effective among asthmatic children, its protective efficacy varies and uptake rates can be low. In comparison, oseltamivir (Tamiflu) is effective against all influenza strains and can reduce the severity and duration of influenza among adults and children. This study determined the effects of oseltamivir among influenza-infected children with asthma. Asthmatic children (6-12 years of age) were randomized to receive oseltamivir (2 mg/kg) or placebo twice daily, as a syrup. The primary efficacy endpoint was the time to freedom from illness. Secondary endpoints included the area under the symptom score-hour curve, the proportion of patients with asthma exacerbations and changes in forced expiratory volume at 1 second during the dosing period. Analysis was performed for both the intent-to-treat infected (n = 179) and per protocol (n = 162) populations. The primary endpoint for this study was not met. Oseltamivir tended to reduce the time to freedom from illness in the intent-to-treat infected population (10.4 hours, 8%; P = 0.5420), the per protocol population (24.3 hours, 17%; P = 0.1607) and patients who started treatment <24 hours after symptom onset (39.8 hours, 25%; P = 0.0780). However, an improvement in pulmonary function was observed. The improvement in forced expiratory volume at 1 second was significantly greater among oseltamivir-treated patients (10.8% versus 4.7%; P = 0.0148). Oseltamivir-treated patients also experienced fewer asthma exacerbations up to day 7 (68% versus 51%; P = 0.031). Oseltamivir was safe and well-tolerated. Oseltamivir is safe and well-tolerated among asthmatic children, may reduce symptom duration and helps improve lung function and reduce asthma exacerbations during influenza infection.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

Suprapubic versus transurethral bladder drainage after surgery for stress urinary incontinence.

Fifty-one patients with clinical and urodynamic diagnoses of stress urinary incontinence were randomly allocated to either suprapubic (N = 24) or transurethral (N = 27) bladder drainage after vaginal surgery for stress incontinence (revised Pereyra procedure). Postoperative use of suprapubic bladder drainage significantly reduced febrile morbidity (calculated as fever index; P less than .01) and length of hospitalization (P less than .05). Postoperative normal bladder functions resumed more quickly when suprapubic drainage was used (P less than .05), so that most patients did not need bladder catheterization upon discharge, as opposed to more than half of those with Foley catheters, who left the hospital with a catheter in place (P less than .05). We conclude that it is both beneficial and cost-effective to use suprapubic bladder drainage after a Pereyra operation for stress urinary incontinence.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

A prospective, randomized trial comparing continuous bladder drainage with catheterization at abdominal hysterectomy.

To compare the infection rate and post-operative morbidity between in-dwelling urinary catheterization and 'in-out' catheterization at the time of routine total abdominal hysterectomy. The study comprised 100 patients who were blindly randomized to have either an indwelling Foley catheter or an 'in-out' catheterization at the time of surgery. Follow-up data on the retention of urine, urinary symptoms and infection were obtained. Of the 95 patients with complete data, 36% of those undergoing in-out catheterization had urinary retention after operation, requiring bladder emptying, compared with 4% of those receiving an indwelling catheter (P < 0.001). In addition, 29% of the catheterized group had urinary tract bacteriuria compared with 13% of the uncatheterized group (P < 0.025). This randomized controlled trial showed that in-out urinary catheterization at the time of routine abdominal hysterectomy was associated with a significantly higher incidence of post-operative urinary retention compared with in-dwelling catheterization, and may have implications for long-term bladder function.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

Visual internal urethrotomy. A prospective controlled trial comparing the results after 3 versus 28 days of postoperative catheterisation.

In a randomized trial, treatment of urethral stricture by direct visual internal urethrotomy with 3 days of postoperative catheterisation was found to be sufficient, given minimal complications, and had a cure rate of 85% after 6 months and 80% after 1 year follow-up. The postoperative follow-up should not include urethrography, but patient's statement and maximal urinary flow rate might be adequate.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

The infusion trial of micturition.

To compare three methods for a trial of micturition (TOM) (the midnight removal of the catheter, dawn removal, and a new infusion method) in a randomized prospective study. A total of 118 consecutive patients who had undergone transurethral resection of the prostate (TURP) or bladder neck incision (BNI) underwent TOM by one of the three methods. In the infusion method, the bladder was filled at a fast-drip rate via the catheter from a bag of normal saline connected by an intravenous supply set. The catheter was then removed, the patient voided and the volume was measured. From the volume of saline remaining, it was possible to calculate the residual volume in the patient. The infusion TOM took a mean 13 h less than the other two methods, which were statistically indistinguishable. The infusion TOM is safe and simple, is quick to carry out and can be performed at any time. It establishes the completeness of bladder emptying, which helps in the assessment of voiding.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

A clinical evaluation of a modified Foley catheter.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

Midnight removal: an improved approach to removal of catheters.

There is no recognised policy regarding the timing of urethral catheter removal, although early morning removal is commonly practised. Removing the catheter at midnight allows patients to return to a normal voiding pattern more rapidly and to leave hospital earlier.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

[Method for transurethral catheterization for 1-3 days for pelvic floor relaxation in the postoperative period].

This clinic trial, randomized and blinded was done to determine efficient whether reducing transurethral Foley catheterization from 3 days to 1 would lead to fewer urinary (UTI) tract infections without retention becoming a problem. Fifty women undergoing vaginal plastic repair to either 1 or 3 days catheterization. Of 25 patients catheterized for both group postoperative urinary retention occurred in 2 (8%) and required a new catheter. Of 25 patients catheterized for 1 day UTI was diagnosed in 1 (4%) and in 5(20) of those catheterized for 3 days, mean postoperative stay was 2 day for patients catheterized for 1 day and 3 days for those for 3 days. The differences are statistically significant, therefore catheter time may safely be reduced to 1 day. This may be associated with a reduced rate postoperative urinary retention, urinary tract infection, and stay postoperative.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

Clinical application of the Bardex IC Foley catheter.

We performed two randomized prospective studies with the silver-coated Bardex IC catheter in order to evaluate the incidence of bacteriuria during short- and medium-term catheterization after urological procedures. During catheterization only consecutive suprapubic urine samples were taken and cultured. After removal of the catheter the patient was allowed one wash-out void, and before the second micturition a suprapubic puncture was performed to collect a culture specimen. In the first trial, after radical prostatectomy 18 patients with the Bardex IC catheter were compared to 17 patients with a silicon catheter after the same procedure. There was no significant difference in bacteriuria after 14 days (50.0 vs. 53.3%). In the second part of the study 180 patients were evaluated 101 with latex and 79 with Bardex IC catheters. The median catheterization time was 5 days. The results show a significant delay in the onset of bacteriuria when a silver alloy catheter is used (p < 0.003). On day 5 only 6.3% had bacteriuria in the Bardex IC group versus 11.9% in the latex group. We conclude that, after urological procedures, short-term catheterization with the Bardex IC catheter is superior to the classical latex catheter.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

Is an indwelling catheter necessary for bladder drainage after modified Burch colposuspension?

Catheterization is considered to be a mandatory procedure for adequate bladder drainage following an anti-incontinence operation until the recovery of normal voiding function occurs. We conducted this prospective study to challenge this practice. A total of 86 patients with genuine stress incontinence who underwent a modified Burch coplosuspension were randomized into two groups based on the day of operation. The study group consisted of 42 patients who had the transurethral Foley catheter removed postoperatively the next morning (Group A). The control group was composed of 43 patients who had the transurethral indwelling catheter left in place until the fifth postoperative day (Group B). The percentages of immediate voiding difficulties in Groups A and B were 7.1% and 0%, respectively ( P>0.05). The postoperative urinary tract infection rates of Groups A and B were 16.6% and 23.3%, respectively ( P>0.05). The success rates of our patients were not compromised after our modified operative procedures (78.6% with dry results and 19.0% with improved symptoms in Group A vs. 74.4% with dry results and 20.9% with improved symptoms in Group B, P >0.05). Our results imply that it is not necessary that an indwelling catheter, for bladder drainage, be left in place until the fifth postoperative day to prevent immediate voiding difficulties.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

Urinary tract infections and asymptomatic bacteriuria after vaginal plastic surgery. A comparison of suprapubic and transurethral catheters.

In a prospective randomized study comprising 90 women undergoing vaginal plastic surgery, suprapubic and transurethral catheter drainage of the bladder were compared regarding urinary tract infection and asymptomatic bacteriuria. No statistically significant differences were found. The mean duration of catheterization was 4.9 days for suprapubic vs 3.3 days for transurethral catheter patients. Postoperative urinary tract infection was diagnosed in 23.7% of patients with suprapubic and in 27.5% of patients with transurethral catheters. Asymptomatic bacteriuria at catheter removal was found in 21.0% of suprapubic and in 12.5% of transurethral catheter patients. More mechanical complications were seen with SPCs than with TUCs. It is concluded that the two methods involve similar risks of infectious complications but that SPCs have a higher rate of mechanical complications.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

Optical internal urethrotomy with and without catheter. A comparative study.

The role of postoperative catheter treatment after optical internal urethrotomy was studied in a prospective, consecutive, randomised series of 54 patients. Group one was treated without catheter and group two with catheter for one day. No significant difference in recurrence rate was found between the two groups studied by means of voiding interview, uroflowmetry and retrograde urethrography.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

Systematic removal of catheter 48 hours following transurethral resection and 24 hours following transurethral incision of prostate: a prospective randomized analysis of 213 patients.

The interval before removal of the catheter used in prostatic transurethral surgery depends to a great extent on the surgeon, with a frequently empirical orientation. We conducted a prospective, randomized and controlled study of 213 patients who underwent transurethral surgery for benign prostatic hyperplasia. The catheter was removed systematically 24 hours after transurethral incision and 48 hours after transurethral resection of the prostate (group 1-52 and 54 patients, respectively) or the catheterization interval was determined by each surgeon in accordance with the usual criteria (group 2-52 and 55 patients, respectively). No statistically significant differences were noted between these 2 groups in regard to complications. We conclude that systematic removal of the catheter at the aforementioned periods is cost-effective, safe and comfortable for the patient.

CD004374

Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

Management of bladder drainage following vaginal plastic repairs.