Treatment of refractory depression with combination reserpine and tricyclic antidepressant therapy

Chronic reserpine use has been reported to precipitate severe depression in some individuals as a result of its amine-depleting action. However, early clinical studies demonstrated that acute administration of high doses of parenteral reserpine in combination with a tricyclic antidepressant could produce rapid improvement in depressive symptoms. Because these early studies defined treatment resistance as failure to respond to a brief course of treatment with a single tricyclic antidepressant, we performed a more stringent, placebo-controlled evaluation of high dose reserpine in nine depressives refractory to at least six previous drug treatments. Overall, neither reserpine nor placebo produced a meaningful decrease in depression ratings within 1 week of treatment; however, one patient did respond to a second course of reserpine. Side effects were mild to moderate in severity, and there were no cases of profound hypotension. Although the efficacy of this drug combination in severely refractory depressives was not confirmed, reserpine may still prove a useful adjunctive agent in some tricyclic-resistant depressed patients.