Are two antidepressant mechanisms better than one?

338 J Clin Psychiatry 58:8, August 1997 © Coyright 997 Phsicians Poraduate Pess, nc. ne pesonal opy ay be pinted New drugs with multiple mechanisms may not only be able to reduce side effects, they might even improve antidepressant efficacy. There is a troubling clinical notion, especially among some investigators, that the SSRIs are not as powerful as the TCAs for treating patients who have severe depression or who are resistant to prior trials of antidepressants. Looking at the pharmacology of the favorite Europe TCA clomipramine, we see that it is both a serotonin and a norepinephrine reuptake inhibitor. Is it possible that the SSRIs went too far by removing he classical antidepressants, namely tricyclic antidepressants (TCAs) and monoamIssue: A drug that combines two or more synergistic mechanisms of action may yield superior therapeutic efficacy or tolerability compared to a single therapeutic mechanism of highly selective agents. Are Two Antidepressant Mechanisms Better Than One?