Cited by 121Bipolar Disorder and TreatmentTreatment of Major DepressionPersonality Disorders and Psychopathology

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Antidepressants worsen rapid-cycling course in bipolar depression: A STEP-BD randomized clinical trial

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El-Mallakh, Rif S., Vöhringer, Paul A., Ostacher, Michael M., Baldassano, Claudia F., Holtzman, Niki S., Whitham, Elizabeth A., Thommi, Sairah B., Goodwin, Frederick K., Ghaemi, S. Nassir·2015·Journal of Affective Disorders

DOI 10.1016/j.jad.2015.04.054PMC PMC4519402

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Abstract

Background The use of antidepressants in rapid-cycling bipolar disorder has been controversial. We report the first randomized clinical trial with modern antidepressants on this topic.Methods As part of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we analyzed, as an a priori secondary outcome, rapid cycling as a predictor of response in 68 patients randomized to continue vs. discontinue antidepressant treatment, after initial response for an acute major depressive episode. Outcomes assessed were percent time well and total number of episodes. All patients received standard mood stabilizers.Results In those continued on antidepressants (AD), rapid cycling (RC) subjects experienced 268% (3.14/1.17) more total mood episodes/year, and 293% (1.29/0.44) more depressive episodes/year, compared with non-rapid cycling (NRC) subjects (mean difference in depressive episodes per year RC vs. NRC was 0.85 ± 0.37 (SE), df = 28, p = 0.03). In the AD continuation group, RC patients also had 28.8% less time in remission than NRC patients (95% confidence intervals (9.9%, 46.5%), p = 0.004). No such differences between RC and NRC subjects were seen in the AD discontinuation group (Table 1). Analyses within the rapid-cycling subgroup alone were consistent with the above comparisons between RC and NRC subjects, stratified by maintenance antidepressant treatment, though limited by sample size.Conclusions In an a priori analysis, despite preselection for good antidepressant response and concurrent mood stabilizer treatment, antidepressant continuation in rapid-cycling was associated with worsened maintenance outcomes, especially for depressive morbidity, vs. antidepressant discontinuation.

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Authors: El-Mallakh, R. S., Vöhringer, P. A., Ostacher, M. M., Baldassano, C. F., Holtzman, N. S., Whitham, E. A., Thommi, S. B., Goodwin, F. K., & Ghaemi, S. N.
Affiliations: Tufts Medical Center (US)
University of Pennsylvania (US)
George Washington University (US)
Tufts University (US)
ORCID: Vöhringer, Paul A.
Baldassano, Claudia F.
Whitham, Elizabeth A.
Ghaemi, S. Nassir
Venue: Journal of Affective Disorders
Publisher: Elsevier BV
Published: 2015-09
Volume: 184
Pages: 318-321
ISSN: 0165-0327 (ISSN-L)
DOI: 10.1016/j.jad.2015.04.054
PMC: PMC4519402
OpenAlex: W1953160278
Cited by: 120
References: 25
Citations by year: 2026: 9 · 2025: 10 · 2024: 15 · 2023: 12 · 2022: 12 · 2021: 9 · 2020: 9 · 2019: 11 · 2018: 11 · 2017: 8 · 2016: 11 · 2015: 3
FWCI: 8.94
Type: journal article
Language: en
Update notices: erratum (2016-01-15)
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Journal of Affective Disorders (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Universidad de Chile (submittedVersion, cc-by-nc-nd)
Funders: NIH (MH-64189)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Social Sciences › Psychology › Clinical Psychology › Personality Disorders and Psychopathology
Keywords: antidepressants, rapid cycling bipolar disorder, bipolar depression, antidepressant discontinuation, depressive episodes, mood stabilizers, STEP-BD, bipolar disorder treatment
MeSH terms: Adult, Antidepressive Agents, Bipolar Disorder, Female, Humans, Male, Symptom Assessment

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Antidepressants worsen rapid-cycling course in bipolar depression: A STEP-BD randomized clinical trial

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