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Published Online: 1 October 2014

The Risk of Switch to Mania in Patients With Bipolar Disorder During Treatment With an Antidepressant Alone and in Combination With a Mood Stabilizer

Alexander Viktorin, M.Sc., Paul Lichtenstein, Ph.D., Michael E. Thase, M.D., Henrik Larsson, Ph.D., Cecilia Lundholm, M.Sc., Patrik K.E. Magnusson, Ph.D., and Mikael Landén, M.D., Ph.D.Authors Info & Affiliations

Publication: American Journal of Psychiatry

Volume 171, Number 10

https://doi.org/10.1176/appi.ajp.2014.13111501

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Abstract

The risk of a manic switch was increased in depressed patients with bipolar disorder who were on antidepressant monotherapy but not in depressed bipolar patients who were treated with an antidepressant and concurrent mood stabilizer.

Abstract

Objective

This study examined the risk of antidepressant-induced manic switch in patients with bipolar disorder treated either with antidepressant monotherapy or with an antidepressant in conjunction with a mood stabilizer.

Method

Using Swedish national registries, the authors identified 3,240 patients with bipolar disorder who started treatment with an antidepressant and had no antidepressant treatment during the previous year. Patients were categorized into those receiving antidepressant monotherapy and those receiving an antidepressant plus a mood stabilizer. A within-individual design was used to control for confounding by disorder severity, genetic makeup, and early environmental factors. Cox regression analyses conditioned on individual were used to compare the rate of mania 0–3 months and 3–9 months after the start of antidepressant treatment with a preceding non-treatment period.

Results

Nearly 35% of the patients were treated with antidepressant monotherapy. The increased risk of treatment-emergent mania was confined to patients on antidepressant monotherapy (hazard ratio=2.83, 95% CI=1.12, 7.19). Among patients treated with a concurrent mood stabilizer, no acute change in risk of mania was observed during the 3 months after the start of antidepressant treatment (hazard ratio=0.79, 95% CI=0.54, 1.15), and a decreased risk was observed during the period 3–9 months after treatment initiation (hazard ratio=0.63, 95% CI=0.42, 0.93).

Conclusions

In this national registry study, antidepressant monotherapy was associated with an increased risk of mania. However, no risk of mania was seen in patients receiving an antidepressant while treated with a mood stabilizer. The results highlight the importance of avoiding antidepressant monotherapy in the treatment of bipolar disorder.

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Information & Authors

Information

Published In

American Journal of Psychiatry

Volume 171 • Number 10 • October 2014

Pages: 1067 - 1073

PubMed: 24935197

History

Received: 15 November 2013

Revision received: 27 March 2014

Accepted: 25 April 2014

Published online: 1 October 2014

Published in print: October 2014

Authors

Affiliations

Alexander Viktorin, M.Sc.

From the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; the Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden; and the Department of Psychiatry, University of Pennsylvania, Philadelphia.

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Paul Lichtenstein, Ph.D.

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Michael E. Thase, M.D.

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Henrik Larsson, Ph.D.

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Cecilia Lundholm, M.Sc.

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Patrik K.E. Magnusson, Ph.D.

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Mikael Landén, M.D., Ph.D.

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Notes

Address correspondence to Dr. Landén ([email protected]).

Funding Information

Dr. Thase has served as a consultant for Alkermes, AstraZeneca, Bristol-Myers Squibb, Cerecor, Eli Lilly, Dey Pharma, Forest Laboratories (including PGx), Gerson Lehman Group, Guidepoint Global, Lundbeck, MedAvante, Merck (including Schering-Plough and Organon), Neuronetics, Ortho-McNeil (including Johnson & Johnson), Otsuka, Pamlab, Pfizer (including Wyeth-Ayerst Pharmaceuticals), PGx, Shire, Sunovion, Supernus, Takeda, and Transcept Pharmaceuticals; he has received grant support from the Agency for Healthcare Research and Quality, Alkermes, Eli Lilly, Forest Pharmaceuticals, NIMH, Otsuka, PharmaNeuroboost, and Roche; he has equity holdings in MedAvante and has received royalties from the American Psychiatric Foundation, Guilford Press, Herald House, and W.W. Norton; his spouse is employed by Peloton Advantage (Formerly Advogent and Embryon), which does business with Pfizer/Wyeth. Dr. Landén has received lecture honoraria from AstraZeneca, Bayer, Biophausia, Bristol-Myers Squibb, and Servier Sweden and has served on an advisory board for Lundbeck. The other authors report no financial relationships with commercial interests.Supported by grants from the Swedish Medical Research Council (K2014-62X-14647-12-51 and K2010-61P-21568-01-4), the Swedish Foundation for Strategic Research, and the Swedish Brain Foundation.

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The Risk of Switch to Mania in Patients With Bipolar Disorder During Treatment With an Antidepressant Alone and in Combination With a Mood Stabilizer

Abstract