This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.


Atypical Antipsychotics in Bipolar Depression: Potential Mechanisms of Action

Lakshmi N. Yatham, MBBS, FRCPC, MRCPsych(UK); Jeffrey M. Goldstein, PhD, MSC; Eduard Vieta, MD, PhD; Charles L. Bowden, MD; Heinz Grunze, MD, PhD; Robert M. Post, MD; Trisha Suppes, MD, PhD; and Joseph R. Calabrese, MD

Published: June 15, 2005

Article Abstract

“Conventional” antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), bupropion,or serotonin-norepinephrine reuptake inhibitors, are not recommended as monotherapy forbipolar depression. Although they are likely to provide effective symptom relief in combination withmood stabilizers, the risk of precipitating a switch to mania often complicates their use even as combinationtherapy. Recently, 2 psychotropic medications approved for treating acute mania, olanzapineand quetiapine, have also been shown to possess antidepressant activity without destabilizing moodand, as such, are potential mood stabilizers. This article aims to review the mechanism of action ofconventional antidepressants and newer agents that are effective in the treatment of bipolar depression.A number of mechanisms have been postulated to play a role in the effective treatment of bipolar depression,including targets as diverse as serotonin (5-HT), norepinephrine, dopamine, γ-aminobutyricacid (GABA), glutamate, and various second messenger signaling pathways. A review of the data revealsan important point of commonality among the antidepressant treatments, olanzapine, and quetiapine.Antidepressant treatments, such as norepinephrine reuptake inhibitors, SSRIs, and electroconvulsivetherapy, induce a reduction of 5-HT2A receptors. Both olanzapine and quetiapine not only areantagonists at this receptor but also induce downregulation of 5-HT2A receptors. It is possible that theantidepressant efficacy of these agents is mediated by this receptor, while the additional benefit ofolanzapine and quetiapine over unimodal antidepressant treatments, in terms of stabilizing mood, maybe provided by their concomitant dopamine D2 antagonism. Further studies should be conducted toexamine these hypotheses.

Some JCP and PCC articles are available in PDF format only. Please click the PDF link at the top of this page to access the full text.

Related Articles

Volume: 66

Quick Links: