Tricyclic antidepressants (TCA) have been shown to be safe and effective in the treatment of neuropathic pain. Commonly used agents include amitriptyline, nortriptyline, imipramine, desipramine. These agents have been studied in double-blind, randomized controlled trials with results suggesting that each of them reduces pain independent of their effect on depression (Portenoy et al. 1984). TCAs are thought to exert their analgesic effect by inhibiting norepinephrine and serotonin reuptake in the central nervous system. Unfortunately, they also effect cholinergic, histaminergic, and adrenergic transmission, resulting in some limiting side effects. These include sedation, orthostasis, cardiac arrhythmia, and urinary retention which may limit their usefulness in certain patient populations, especially the elderly.
Since the introduction of tricyclic antidepressants, a number of newer generation of antidepressants have been developed. The selective serotonin and norepinephrine reuptake inhibitors (SNRI) are among the newest class of antidepressants, and their ability to reduce pain in various neuropathic syndromes has also been examined.
Duloxetine (Cymbalta®; Eli Lily, Indianapolis, IN) has recently been approved by the Food and Drug Administration (FDA) for the treatment of diabetic neuropathic pain. Goldstein and coworkers (Allen 2008) reported on a randomized trial of 457 patients treated for 12 weeks with 20, 60, or 120 mg a day of duloxetine. The 60 and 120 mg a day doses demonstrated greater improvement than placebo in the 24-h average pain score beginning 1 week after randomization. Duloxetine has a similar pharmacology to venlafaxine in that it is a reuptake inhibitor for serotonin and norepinephrine. It differs from venlafaxine in that it is a norepinephrine reuptake inhibitor at lower doses. The clinical significance of this difference has yet to be demonstrated; however, there is clinical evidence that venlafaxine is also useful in the treatment of neuropathic pain syndromes (Guldiken et al. 2004, Yucel et al. 2005).
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