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Published Online: 31 January 2017

Switch Rates During Acute Treatment for Bipolar II Depression With Lithium, Sertraline, or the Two Combined: A Randomized Double-Blind Comparison

Lori L. Altshuler, M.D., Catherine A. Sugar, Ph.D., Susan L. McElroy, M.D., Brian Calimlim, Dr.P.H., Michael Gitlin, M.D., Paul E. Keck, Jr., M.D., Ana Aquino-Elias, B.S., Brian E. Martens, B.S.S.W., M.S., E. Grace Fischer, B.S., Teri L. English, B.A., Janine Roach, M.D., and Trisha Suppes, M.D., Ph.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 174, Number 3
https://doi.org/10.1176/appi.ajp.2016.15040558
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Abstract

Objective:

The authors compared medication-induced mood switch risk (primary outcome), as well as treatment response and side effects (secondary outcomes) with three acute-phase treatments for bipolar II depression.

Method:

In a 16-week, double-blind, multisite comparison study, 142 participants with bipolar II depression were randomly assigned to receive lithium monotherapy (N=49), sertraline monotherapy (N=45), or combination treatment with lithium and sertraline (N=48). At each visit, mood was assessed using standardized rating scales. Rates of switch were compared, as were rates of treatment response and the presence and severity of treatment-emergent side effects.

Results:

Twenty participants (14%) experienced a switch during the study period (hypomania, N=17; severe hypomania, N=3). Switch rates did not differ among the three treatment groups, even after accounting for dropout. No patient had a manic switch or was hospitalized for a switch. Most switches occurred within the first 5 weeks of treatment. The treatment response rate for the overall sample was 62.7% (N=89), without significant differences between groups after accounting for dropout. The lithium/sertraline combination group had a significantly higher overall dropout rate than the monotherapy groups but did not have an accelerated time to response.

Conclusions:

Lithium monotherapy, sertraline monotherapy, and lithium/sertraline combination therapy were associated with similar switch and treatment response rates in participants with bipolar II depression. The dropout rate was higher in the lithium/sertraline combination treatment group, without any treatment acceleration advantage.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Volume 174 • Number 3 • March 01, 2017
Pages: 266 - 276
PubMed: 28135846

History

Received: 29 April 2015
Revision received: 27 March 2016
Accepted: 31 October 2016
Published online: 31 January 2017
Published in print: March 01, 2017

Keywords

  1. Antidepressants
  2. Clinical Drug Studies
  3. Drug Side Effects-Other
  4. Lithium
  5. Bipolar II Disorder
  6. Bipolar Depression

Authors

Affiliations

Lori L. Altshuler, M.D.
From the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles; the Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles; the Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles; the Department of Biostatistics, School of Public Health, University of California, Los Angeles; the Lindner Center of HOPE, Mason, Ohio; the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati; the Department of Psychiatry and Biobehavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the VA Palo Alto Health Care System, Palo Alto, Calif.; and the Department of Psychiatry, Olive View–UCLA Medical Center, Sylmar, Calif.
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Catherine A. Sugar, Ph.D.
From the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles; the Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles; the Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles; the Department of Biostatistics, School of Public Health, University of California, Los Angeles; the Lindner Center of HOPE, Mason, Ohio; the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati; the Department of Psychiatry and Biobehavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the VA Palo Alto Health Care System, Palo Alto, Calif.; and the Department of Psychiatry, Olive View–UCLA Medical Center, Sylmar, Calif.
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Susan L. McElroy, M.D.
From the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles; the Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles; the Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles; the Department of Biostatistics, School of Public Health, University of California, Los Angeles; the Lindner Center of HOPE, Mason, Ohio; the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati; the Department of Psychiatry and Biobehavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the VA Palo Alto Health Care System, Palo Alto, Calif.; and the Department of Psychiatry, Olive View–UCLA Medical Center, Sylmar, Calif.
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Brian Calimlim, Dr.P.H.
From the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles; the Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles; the Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles; the Department of Biostatistics, School of Public Health, University of California, Los Angeles; the Lindner Center of HOPE, Mason, Ohio; the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati; the Department of Psychiatry and Biobehavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the VA Palo Alto Health Care System, Palo Alto, Calif.; and the Department of Psychiatry, Olive View–UCLA Medical Center, Sylmar, Calif.
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Michael Gitlin, M.D.
From the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles; the Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles; the Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles; the Department of Biostatistics, School of Public Health, University of California, Los Angeles; the Lindner Center of HOPE, Mason, Ohio; the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati; the Department of Psychiatry and Biobehavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the VA Palo Alto Health Care System, Palo Alto, Calif.; and the Department of Psychiatry, Olive View–UCLA Medical Center, Sylmar, Calif.
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Paul E. Keck, Jr., M.D.
From the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles; the Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles; the Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles; the Department of Biostatistics, School of Public Health, University of California, Los Angeles; the Lindner Center of HOPE, Mason, Ohio; the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati; the Department of Psychiatry and Biobehavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the VA Palo Alto Health Care System, Palo Alto, Calif.; and the Department of Psychiatry, Olive View–UCLA Medical Center, Sylmar, Calif.
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Ana Aquino-Elias, B.S.
From the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles; the Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles; the Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles; the Department of Biostatistics, School of Public Health, University of California, Los Angeles; the Lindner Center of HOPE, Mason, Ohio; the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati; the Department of Psychiatry and Biobehavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the VA Palo Alto Health Care System, Palo Alto, Calif.; and the Department of Psychiatry, Olive View–UCLA Medical Center, Sylmar, Calif.
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Brian E. Martens, B.S.S.W., M.S.
From the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles; the Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles; the Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles; the Department of Biostatistics, School of Public Health, University of California, Los Angeles; the Lindner Center of HOPE, Mason, Ohio; the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati; the Department of Psychiatry and Biobehavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the VA Palo Alto Health Care System, Palo Alto, Calif.; and the Department of Psychiatry, Olive View–UCLA Medical Center, Sylmar, Calif.
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E. Grace Fischer, B.S.
From the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles; the Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles; the Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles; the Department of Biostatistics, School of Public Health, University of California, Los Angeles; the Lindner Center of HOPE, Mason, Ohio; the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati; the Department of Psychiatry and Biobehavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the VA Palo Alto Health Care System, Palo Alto, Calif.; and the Department of Psychiatry, Olive View–UCLA Medical Center, Sylmar, Calif.
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Teri L. English, B.A.
From the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles; the Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles; the Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles; the Department of Biostatistics, School of Public Health, University of California, Los Angeles; the Lindner Center of HOPE, Mason, Ohio; the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati; the Department of Psychiatry and Biobehavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the VA Palo Alto Health Care System, Palo Alto, Calif.; and the Department of Psychiatry, Olive View–UCLA Medical Center, Sylmar, Calif.
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Janine Roach, M.D.
From the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles; the Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles; the Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles; the Department of Biostatistics, School of Public Health, University of California, Los Angeles; the Lindner Center of HOPE, Mason, Ohio; the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati; the Department of Psychiatry and Biobehavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the VA Palo Alto Health Care System, Palo Alto, Calif.; and the Department of Psychiatry, Olive View–UCLA Medical Center, Sylmar, Calif.
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Trisha Suppes, M.D., Ph.D.
From the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles; the Jane and Terry Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles; the Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles; the Department of Biostatistics, School of Public Health, University of California, Los Angeles; the Lindner Center of HOPE, Mason, Ohio; the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati; the Department of Psychiatry and Biobehavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the VA Palo Alto Health Care System, Palo Alto, Calif.; and the Department of Psychiatry, Olive View–UCLA Medical Center, Sylmar, Calif.
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Notes

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

Funding Information

National Institute of Mental Health10.13039/100000025: 5R01MH074707, 5R01MH074928, 5R01MH074929
Supported by a collaborative R01 grant by the NIMH: 5R01MH074707 (to Dr. Altshuler at UCLA Medical Center and VA Greater Los Angeles Healthcare System), 5R01MH074929 (to Dr. McElroy at University of Cincinnati College of Medicine and the Lindner Center of HOPE), and 5R01MH074928 (to Dr. Suppes at the University of Texas Southwestern Medical Center, Dallas, and the VA Palo Alto Health Care System, Palo Alto).Dr. McElroy is a consultant to or scientific advisory board member for Bracket, Hoffmann–La Roche, MedAvante, Myriad, Naurex, Novo Nordisk, Shire, and Sunovion; she is a principal or co-investigator on studies sponsored by Alkermes, Forest, the Marriott Foundation, Naurex, NIMH, Orexigen Therapeutics, Shire, Sunovion, and Takeda; she is an inventor on U.S. patent no. 6,323,236 B2 (Use of Sulfamate Derivatives for Treating Impulse Control Disorders) and, along with the patent’s assignee, University of Cincinnati, has received payments from Johnson & Johnson, which has exclusive rights under the patent. Dr. Gitlin has been on speakers bureaus for and received honoraria and travel expenses from Bristol-Myers Squibb and Otsuka. Dr. Keck is a co-inventor on U.S. patent no. 6,387,956 (a method of treating obsessive-compulsive spectrum disorder that includes administering an effective amount of tramadol), for which he has received no financial benefit. Dr. Suppes has received research funding from Elan, NIMH, Pathway Genomics, Stanley Medical Research Institute, Sunovion Pharmaceuticals, and the VA Cooperative Studies Program; has served as a consultant or an advisory board member for A/S H. Lundbeck, Merck, and Sunovion Pharmaceuticals; and has received royalties from Jones & Bartlett and UpToDate. The other authors report no financial relationships with commercial interests.

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