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Correlations With the Neurobiologic Actions of Tricyclic Antidepressant Drugs and Lithium Ion on the Serotonin System

Claude de Montigny, MD, PhD, FRCP(C); Gèrard Cournoyer, MD; Raymond Morissette, MD, FRCP(C); Robert Langlois, MD, CSPQ; Gilles Caillè, PhD

Arch Gen Psychiatry. 1983;40(12):1327-1334.

Abstract
• Preliminary reports suggested that the addition of lithium carbonate to the regimen of patients treated with, but not responding to, a tricyclic antidepressant (TCA) drug can induce a rapid alleviation of depression. We examined the effect of lithium carbonate addition in 39 patients with unipolar depression whose conditions were not improved by at least three weeks' TCA drug administration. In 30 of 42 observations, lithium carbonate brought about a greater than 50% improvement within 48 hours. In a second study, the effects of lithium carbonate addition were compared in five amitriptyline hydrochloride—pretreated and five placebo-pretreated patients who showed no improvement after a three-week treatment. All five patients receiving amitriptyline showed a greater than 50% improvement 48 hours after lithium carbonate addition, whereas only one patient in the placebo group showed a marked response. In a third study the effect of lithium carbonate withdrawal was studied in nine TCA-resistant patients who had shown a marked improvement 48 hours after lithium addition. Only five of these patients had a relapse five days after lithium discontinuation. Since animal studies have shown that TCA drugs sensitize forebrain neurons to serotonin and that lithium enhances the activity of serotonin-containing neurons, we propose that the antidepressant effect of lithium addition in TCA-resistant patients might be mediated by enhancing serotonin neurotransmission.

Author Affiliations
From the Psychiatric Research Center, Louis-H Lafontaine Hospital, Montreal (Drs de Montigny, Cournoyer, Morissette, Langlois, and Caillè), and the Neuroscience Research Center, Faculty of Medicine, University of Montreal (Dr de Montigny).

Footnotes
Accepted for publication June 14, 1983.

Presented in part at the American Psychiatric Association meeting, Toronto, May 19, 1982.

Reprint requests to Neuroscience Research Center, Faculty of Medicine, University of Montreal, PO Box 6128, Station A, Montreal, Quebec, Canada H3C 3J7.

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