Pain relief in diabetic neuropathy: the effectiveness of imipramine and related drugs.

Experience of treating 80 consecutive patients with painful diabetic neuropathy and a double-blind study of imipramine in acute painful neuropathy are reported. A standard stepwise protocol was used, based on imipramine as the drug of first choice, substitution of amitriptyline or mianserin as second choice, and, thirdly, addition of phenothiazine or clonazepam if necessary. Sixty per cent were satisfied with imipramine alone and all but 3 (5%) were improved by the stepwise scheme. Paradoxically, the most effective analgesia was obtained in those with the most severe and unpleasant pain. Often 150 mg of imipramine or amitriptyline was necessary. The onset of analgesia and relapse after withdrawal of treatment were rapid, facilitating clinical use, and suggesting a peripheral rather than central drug action.