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.

Single doses of the serotonin agonists buspirone and m-chlorophenylpiperazine do not relieve neuropathic pain.

A large body of evidence links serotonin with analgesia in animal models, but the lack of serotonin agonists suitable for clinical use has delayed study of serotonin's relevance to pain relief in humans. In a randomized, double-blind crossover study, we compared single doses of two 5-HT1 agonists, buspirone and m-chlorophenylpiperazine, to placebo in 20 patients with post-herpetic neuralgia or painful neuropathy. No analgesia was observed after either drug, at doses high enough to produce frequent central nervous system side effects. These results suggest that acute stimulation of 5-HT1 receptors is not sufficient to produce analgesia in patients with these neuropathic pain syndromes.