Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer. The analgesic effect of amitriptyline on chronic facial pain. A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia. Amitriptyline in neuropathic cancer pain in patients on morphine therapy: a randomized placebo-controlled, double-blind crossover study. Amitriptyline in the treatment of chemotherapy-induced neuropathic symptoms. Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. A randomized, double-blind clinical trial. Does addition of low-dose flupentixol enhance the analgetic effects of low-dose amitriptyline in somatoform pain disorder? Nortriptyline versus amitriptyline in postherpetic neuralgia: a randomized trial. A pilot study examining topical amitriptyline, ketamine, and a combination of both in the treatment of neuropathic pain. Efficacy of amitriptyline for relief of pain in spinal cord injury: results of a randomized controlled trial. Topical 2% amitriptyline and 1% ketamine in neuropathic pain syndromes: a randomized, double-blind, placebo-controlled trial. A randomized, controlled trial of amitriptyline and naproxen in the treatment of patients with fibromyalgia. Comparison of the effectiveness of amitriptyline and gabapentin on chronic neuropathic pain in persons with spinal cord injury. A randomized, double-blind, placebo-controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder. Randomized double-blind study comparing the efficacy and safety of lamotrigine and amitriptyline in painful diabetic neuropathy. Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain. Central post-stroke pain--a controlled trial of amitriptyline and carbamazepine. Evaluation of amitriptyline in primary fibrositis. A double-blind, placebo-controlled study. Amitriptyline versus maprotiline in postherpetic neuralgia: a randomized, double-blind, crossover trial. Multicenter, randomized, placebo-controlled trial of amitriptyline in children with functional gastrointestinal disorders.
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. 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. To study the effect of fluoxetine (FL) and amitriptyline (AM), alone and in combination, in patients with fibromyalgia (FM).
                Nineteen patients with FM completed a randomized, double-blind crossover study, which consisted of 4 6-week trials of FL (20 mg), AM (25 mg), a combination of FL and AM, or placebo. Patients were evaluated on the first and last day of each trial period. Outcome measures included a tender point score, the Fibromyalgia Impact Questionnaire (FIQ), the Beck Depression Inventory (BDI) scale, and visual analog scales (VAS) for global well-being (1 completed by the physician and 1 by the patient), pain, sleep trouble, fatigue, and feeling refreshed upon awakening.
                Both FL and AM were associated with significantly improved scores on the FIQ and on the VAS for pain, global well-being, and sleep disturbances. When combined, the 2 treatments worked better than either medication alone. Similar, but nonsignificant, improvement occurred in the BDI scale, the physician global VAS, and the VAS for fatigue and feeling refreshed upon awakening. Trends were less clear for the tender point score.
                Both FL and AM are effective treatments for FM, and they work better in combination than either medication alone. 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. Neuropathy is common in patients receiving vinca alkaloids, platinum derivatives, or taxanes. This double-blind, randomized, placebo-controlled study assessed the efficacy of low-dose amitriptyline to relieve chemotherapy-induced symptoms in 44 patients (age 20-65 years) who had neuropathic symptoms (numbness, tingling, pain) with a severity of > or =3/10. They were treated with amitriptyline for eight weeks (10mg/day to start, then dose elevation of 10mg/week up to 50mg/day if tolerated, followed by a stable dose > or =4 weeks). The patients completed a diary twice weekly, noting the intensity of pain, numbness and tingling, global improvement, and adverse effects. Neurological examination was performed at each visit (baseline, four, and eight weeks). The patients assessed both intensity and relief of pain, and overall discomfort. They also completed the Neuropathic Pain Scale and validated measures of anxiety and depression, and quality of life (QoL). The results demonstrated that amitriptyline did not improve sensory neuropathic symptoms, although there was a trend toward global improvement and improved QoL in favor of the amitriptyline group. No statistical significance was reached, probably due to the small number of patients and too low dose of amitriptyline. Amitriptyline was well tolerated. To compare the relative efficacy and tolerability of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia, and to identify predictors of response to amitriptyline and cyclobenzaprine.
                Two hundred eight patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered into a 6-month prospective, double-blind, multicenter trial and were randomized to 1 of 3 treatment groups: amitriptyline, cyclobenzaprine, or placebo.
                After 1 month, 21%, 12%, and 0% of the amitriptyline, cyclobenzaprine, and placebo patients, respectively, had significant clinical improvement (amitriptyline versus placebo P = 0.002, cyclobenzaprine versus placebo P = 0.02, amitriptyline versus cyclobenzaprine P not significant). These percentages increased to 36%, 33%, and 19%, respectively, at the 6-month assessment (P not significant). The nature and frequency of side effects reported by patients treated with amitriptyline and those reported by patients treated with cyclobenzaprine were similar. A normal Minnesota Multiphasic Personality Inventory (MMPI) profile at baseline was predictive of clinical improvement at the 1-month evaluation (odds ratio 3.3, 95% confidence interval 1.2-9.0). However, neither the MMPI profile nor any of the demographic, clinical, or functional parameters evaluated at baseline predicted long-term response.
                Our data confirm the short-term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia. Long-term efficacy could not be demonstrated because of a higher-than-expected placebo response. Predictors of response to these drugs could not be determined. In a double-blind, crossover study, the effects of 75 mg amitriptyline alone during 5 weeks on pain intensity were compared with the effects of a combination of 75 mg amitriptyline and 3 mg flupentixol during 5 weeks in 34 patients with somatoform pain disorder. Both treatments resulted in a statistically significant reduction in pain. However, pain reduction in the combined treatment did not differ from that in the treatment with amitriptyline as a single drug. Neither tardive dyskinesias nor other serious side effects were observed. The results do not support the clinical practice of adding low-dose neuroleptics to low-dose antidepressants in the treatment of somatoform pain disorder. 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. The involvement of ongoing peripheral activity in the generation of nociceptive input in neuropathic pain suggests that topical drug delivery may be useful as a treatment strategy. This is a pilot study providing initial information regarding the use of novel topical preparations containing amitriptyline (AMI), ketamine (KET), and a combination of both in the treatment of neuropathic pain.
                The study design included a 2 day randomized, double blind, placebo controlled, 4 way cross-over trial of all treatments, followed by an open label treatment phase using the combination cream for 7 days. Twenty volunteers with chronic neuropathic pain were randomly assigned to treatment order and applied 5 mls of each topical treatment (1% AMI, 0.5% KET, combination AMI 1%/KET 0.5%, and placebo) for 2 days. Measures of pain at the end of each block included the short form McGill Pain Questionnaire (MPQ) and visual analog scales (VAS) for present pain intensity and pain relief. Eleven subjects who judged subjective improvement from any treatment in the initial trial entered the open-label trial and used the combination cream for 7 days. Pain levels were recorded daily using the same measures. Blood levels for amitriptyline and ketamine were performed at 7 days to determine whether systemic absorption had occurred.
                There was no statistically significant difference from placebo after 2 days for any treatment during the double blind component of the trial. In the 11 subjects who used the combination cream, there was a statistically significant effect, with subjects reporting significantly greater analgesia by days 3 to 7 according to measures of pain and pain relief. Blood levels revealed that there was no significant systemic absorption of amitriptyline or ketamine. Only 2 subjects experienced side effects; these were minor and did not lead to discontinuation of the cream.
                This pilot study demonstrated a lack of effect for all treatments in the 2 day double blind placebo controlled trial, followed by analgesia in an open label trial in a subgroup of subjects who chose to use the combination cream for 7 days. Blood analysis revealed no significant systemic absorption of either agent after 7 days of treatment, and creams were well tolerated. A larger scale randomized trial over a longer interval is warranted to examine further effects observed in the open label 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. A double-blind, randomized, placebo-controlled 3-week study evaluated the efficacy of topical 2% amitriptyline, 1% ketamine, and a combination of both in treating patients with neuropathic pain.
                Ninety-two patients with diabetic neuropathy, postherpetic neuralgia, or postsurgical/posttraumatic neuropathic pain with allodynia, hyperalgesia, or pinprick hypesthesia were randomly assigned to receive one of four creams (placebo, 2% amitriptyline, 1% ketamine, or 2% amitriptyline-1% ketamine combined). The primary outcome measure was change in average daily pain intensity (baseline week vs. final week) using an 11-point numerical pain rating scale. Secondary outcomes included the McGill Pain Questionnaire, measures of allodynia and hyperalgesia, and patient satisfaction.
                A reduction in pain scores of 1.1-1.5 units was observed in all groups, and there was no difference between groups. Blood concentrations revealed no significant systemic absorption. Minimal side effects were encountered.
                This randomized, placebo-controlled trial examining topical 2% amitriptyline, 1% ketamine, and a combination in the treatment of neuropathic pain revealed no difference between groups. Optimization of doses may be required, because another study has revealed that higher concentrations of these agents combined do produce significant analgesia. Sixty-two patients with fibromyalgia were randomly assigned to receive 25 mg of amitriptyline at night, 500 mg of naproxen twice daily, both amitriptyline and naproxen, or placebo in a 6-week, double-blind trial. Amitriptyline was associated with significant improvement in all outcome parameters, including patient and physician global assessments, patient pain, sleep difficulties, fatigue on awakening, and tender point score. Patients taking the combined naproxen-amitriptyline regimen experienced minor, but not significant, improvement in pain when compared with patients who took amitriptyline alone. Amitriptyline, or amitriptyline and naproxen, is an effective therapeutic regimen for patients with fibromyalgia. To test the hypotheses that both amitriptyline and gabapentin are more effective in relieving neuropathic pain than an active placebo, diphenhydramine.
                Randomized, controlled, double blind, triple crossover 8-week trial.
                Veterans Affairs medical center.
                Community dwelling adults with spinal cord injury (N=38) were recruited by telephone, letters, and flyers.
                Eight-week trial each of amitriptyline, gabapentin, and diphenhydramine.
                Pain intensity measured with a 10-cm visual analog scale (VAS) and an 11-point (0-10) numeric rating scale (NRS) and depressive symptomatology measured with the Center for Epidemiologic Studies Depression Scale-Short Form (CESD-SF).
                Baseline VAS scores for participants with low (< 10) CESD-SF scores was 4.61 and for those with high scores (> or = 10) it was 7.41. At week 8, in participants with high baseline CESD-SF scores, amitriptyline (mean, 4.21) was more effective than diphenhydramine (mean, 6.67; P=.035), and there was a nonsignificant trend suggesting that amitriptyline may be more effective than gabapentin (mean, 6.68; P=.061). Gabapentin was no more effective than diphenhydramine (P=.97). There was no significant difference among the medications for those with lower CESD-SF scores. Results could not be attributed to dropout rates, order or dose of medications, amount of medication taken for breakthrough pain, or side effects.
                Amitriptyline is more efficacious in relieving neuropathic pain than diphenhydramine at or below the level of spinal cord injury in people who have considerable depressive symptomatology. To study the usefulness of moclobemide and amitriptyline in the treatment of fibromyalgia (FM) in females without psychiatric disorder.
                In the present four centre, 12 week study, 130 female FM patients not suffering from psychiatric disorders were randomized to receive amitriptyline (AMI; 25 37.5 mg), moclobemide (MOCLO; 450-600 mg) or identical placebo.
                Seventy-four, 54 and 49 per cent of patients on AMI, MOCLO and placebo, respectively, were judged as responders. The patients on AMI also managed best regarding the respective improvements during the trial in general health, pain, sleep quality and quantity, and fatigue on visual analogue scales (VAS), the areas of the Nottingham Health Profile (NHP), as well as in the three Sheehan's functional disability scales. In the within-group comparisons, MOCLO also improved pain assessed both on VAS and on the NHP pain dimension, but the improvement was invalidated by the poor success of the drug with regard to sleep. The tolerabilities of all three drugs were comparable.
                The study indicates that MOCLO may not be helpful in FM patients free from clinically meaningful psychiatric problems. To compare the efficacy and safety of lamotrigine and amitriptyline in controlling chronic painful peripheral neuropathy in diabetic patients.
                A randomized, double-blind, crossover, active-control, clinical trial with variable dose titration was carried out (n = 53). Amitriptyline orally, at doses of 10, 25 and 50 mg at night-time, each dose for 2 weeks, and lamotrigine orally, at doses of 25, 50 and 100 mg twice daily, each dose for 2 weeks, by optional titration were used. There was a placebo washout period for 2 weeks between the two drugs. Assessment for pain relief, overall improvement and adverse events were carried out.
                Good, moderate and mild pain relief were noted in 19 (41%), six (13%) and seven (15%) patients on lamotrigine and 13 (28%), five (11%) and 15 (33%) patients on amitriptyline, respectively, by patient's global assessment of efficacy and safety. Patient and physicians global assessment, McGill pain questionnaire and Likert pain scale showed no significant difference between the treatments, although improvement with both treatments was seen from 2 weeks. Of the 44 adverse events reported, 33 (75%) were with amitriptyline, sedation being the commonest [in 19 (43%) patients]. Lamotrigine caused adverse events in 11 (25%), of which rash in three (7%) and elevations of creatinine in four (9%) were the most common. The preferred lamotrigine dose was 25 mg twice daily.
                As there are few differences between the two treatments in efficacy, lamotrigine 25 mg twice daily might be the first choice as it is associated with fewer adverse effects in our population. 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. 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. Seventy patients with primary fibrositis satisfying Smythe's criteria were studied in a 9-week double-blind trial comparing 50 mg amitriptyline with placebo. Fifty-nine patients completed the trial: 27 were treated with amitriptyline, and 32 took a placebo. The patients who received amitriptyline improved significantly in their morning stiffness and pain analog scores at 5 and 9 weeks, compared with baseline scores, whereas no changes were noted in these parameters in the placebo group. Fibrocytic point tenderness did not improve significantly in either of the treatment groups. When compared with the placebo group, the amitriptyline group improved significantly with respect to sleep pattern and patient and physician global assessments. Our data indicate that amitriptyline has some therapeutic benefit in patients with primary fibrositis. 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. There are no prospective, multicenter, double-blind, placebo-controlled, randomized pharmacologic trials for the treatment of pain-predominant functional gastrointestinal disorders in children. The aim of this study was to evaluate the efficacy of amitriptyline in children with pain-predominant functional gastrointestinal disorders.
                In this multicenter placebo-controlled trial, children with irritable bowel syndrome, functional abdominal pain, or functional dyspepsia were randomized to 4 weeks of placebo or amitriptyline (10 mg/d, weight <35 kg; 20 mg/d, weight >35 kg). Assessment of gastrointestinal symptoms, psychological traits, and daily activities occurred before and after intervention. Pain was assessed daily with self-report diaries. The primary outcome was overall response to treatment (child's assessment of pain relief and sense of improvement). Secondary outcomes were effect on psychosocial traits and daily functioning.
                Ninety children were enrolled, and 83 completed the study (placebo, 40 children [30 girls]; drug, 43 children [35 girls]). A total of 63% of patients reported feeling better and 5% feeling worse in the amitriptyline arm compared with 57.5% feeling better and 2.5% feeling worse in the placebo arm (P = .63). Pain relief was excellent in 7% and good in 38% of children receiving placebo compared with excellent in 15% and good in 35% of children treated with amitriptyline (P = .85). Logistic regression analysis of those reporting excellent or good response versus fair, poor, or failed response showed no difference between amitriptyline and placebo (P = .83). Children who had more severe pain at baseline in both groups (P = .0065) had worse outcome. Amitriptyline reduced anxiety scores (P < .0001).
                Both amitriptyline and placebo were associated with excellent therapeutic response. There was no significant difference between amitriptyline and placebo after 4 weeks of treatment. Patients with mild to moderate intensity of pain responded better to treatment.
Amitriptyline has been a first-line treatment for neuropathic pain for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against decades of successful treatment in many patients with neuropathic pain or fibromyalgia. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect. Amitriptyline should continue to be used as part of the treatment of neuropathic pain or fibromyalgia, but only a minority of patients will achieve satisfactory pain relief. Limited information suggests that failure with one antidepressant does not mean failure with all.
It is unlikely that any large randomised trials of amitriptyline will be conducted in specific neuropathic pain conditions or in fibromyalgia to prove efficacy.