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A review of FDA-approved treatment options in bipolar depression

Published online by Cambridge University Press:  15 November 2013

Roger S. McIntyre ,
Danielle S. Cha ,
Rachael D. Kim  and
Rodrigo B. Mansur
Roger S. McIntyre*
Affiliation:
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
Danielle S. Cha
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
Rachael D. Kim
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada
Rodrigo B. Mansur
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada
*
*Correspondence to: Roger S. McIntyre, University of Toronto, 399 Bathurst Street, Toronto, ON, Canada M5 T 2S8. (Email: roger.mcintyre@uhn.on.ca)
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Abstract

Objectives/Introduction

Herein we review the evidence supporting Food and Drug Administration (FDA) approved and emerging treatments for bipolar depression.

Methods

A PubMed search of all English-language articles published up to July 2013 was conducted. The search terms were quetiapine, olanzapine-fluoxetine, olanzapine, lurasidone, ketamine, modafinil/armodafinil, and lamotrigine. The search was augmented with a manual review of relevant article reference lists, as well as posters presented at national and international meetings. Articles selected for review were based on the adequacy of sample size, the use of standardized diagnostic instruments, validated assessment measures, and overall manuscript quality.

Results

Olanzapine-fluoxetine combination (OFC), quetiapine, and lurasidone are FDA-approved for the acute treatment of bipolar depression. Lurasidone is the most recently approved agent for bipolar depression. Olanzapine-fluoxetine combination and quetiapine are approved as single modality therapies while lurasidone is approved as a monotherapy and as an adjunct to lithium or divalproex. The overall effect size of the 3 treatments in mitigating depressive symptoms is similar. Clinically significant weight gain and metabolic disruption as well as sedation are significant limitations of OFC and quetiapine. The minimal propensity for weight gain as well as the metabolic neutrality of lurasidone in the bipolar population is a clinically significant advantage. Evidence also supports lamotrigine with compelling evidence as an adjunct to lithium and in recurrence prevention paradigm; suggested evidence also exists for ketamine and modafinil/armodafinil; notwithstanding, these treatments remain investigational.

Conclusion

Relatively few agents are FDA-approved for bipolar depression. The selection and sequencing of agents in bipolar depression should give primacy to those agents that are FDA-approved. Further refinement of the selection process will need to pay careful attention to the relative hazards of weight gain and metabolic disruption in this highly susceptible population. Other agents with differential mechanisms (eg, ketamine) offer a promising alternative in bipolar depression.

Keywords

Antipsychoticsarmodafinilketaminelurasidonemodafinilolanzapine-fluoxetinequetiapine
Type
CME Review Article
Information
CNS Spectrums , Volume 18 , Issue s1: CME SUPPLEMENT , December 2013 , pp. 1 - 21
Copyright
Copyright © Cambridge University Press 2013 

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Footnotes

This activity is supported by an educational grant from Sunovion Pharmaceuticals Inc.

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