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.