When the tricyclic antidepressants amitriptyline and desipramine (Norpramin) were compared with placebo, one of every two patients treated experienced at least moderate relief of neuropathic pain (number needed to treat = 2). However, multiple studies comparing tricyclic antidepressants found no evidence that one was superior to another. No high-quality evidence comparing tricyclic antidepressants with anticonvulsants was found.

The Cochrane review also evaluated studies with respect to specific causes of neuropathic pain. There was good evidence for the effect of tricyclic antidepressants for diabetic neuropathy, but only limited evidence of effectiveness was available regarding the selective serotonin reuptake inhibitors (SSRIs) fluoxetine (Prozac), citalopram (Celexa), and paroxetine (Paxil). There also was evidence that tricyclic antidepressants are effective for postherpetic neuralgia. There was some evidence of benefit from tricyclic antidepressants for central neuropathic pain, but tricyclic antidepressants were not effective in HIV neuropathy.

Treatment recommendations from the Fourth International Conference on the Mechanisms and Treatment of Neuropathic Pain, published in the Archives of Neurology, advocate five options for the initial treatment of neuropathic pain: tricyclic antidepressants, gabapentin, 5% lidocaine patch (Lidoderm), opioids, and tramadol (Ultram). (2) This conference was sponsored by the manufacturer of the 5% lidocaine patch. The recommendations cite evidence supporting the use of gabapentin for postherpetic neuralgia, diabetic neuropathy, and mixed neuropathic pain syndromes; the lidocaine patch for postherpetic neuralgia; opioids for postherpetic neuralgia and diabetic neuropathy; and tramadol for diabetic neuropathy and painful polyneuropathy. They also note that although tricyclic antidepressants were the first medications to be demonstrated effective for neuropathic pain in placebo-controlled trials, they must be used cautiously because of the potential for adverse effects. (2)

The best evidence on antidepressants for neuropathic pain supports the use of tricyclic antidepressants for painful diabetic neuropathy and postherpetic neuralgia. Tricyclic antidepressants should be used with caution in older persons because of the potential for adverse effects including drowsiness, dry mouth, blurred vision, constipation, and urinary retention, (1) and caution also is required in patients with underlying cardiovascular disease, glaucoma, or autonomic neuropathy. (2) Although anticonvulsants also have been demonstrated effective for neuropathic pain, there is no good evidence comparing the relative safety and effectiveness of tricyclic antidepressants with anticonvulsants or other agents for neuropathic pain. Selection of an agent for treating neuropathic pain should be guided by the underlying diagnosis, an awareness of any comorbid conditions or risk factors, and patient preference.

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