Antidepressants worsen rapid-cycling course in bipolar depression: A STEP-BD randomized clinical trial
Open accessAbstract
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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Antidepressants have been shown to destabilize patients with rapid cycling BDI, even with concurrent mood stabilizer use.
“Antidepressants are not recommended, as they have been shown to destabilize patients, even with concurrent mood stabilizer use.324”
From Canadian Network for Mood and Anxiety Treatments ( <scp>CANMAT</scp> ) and International Society for Bipolar Disorders ( <scp>ISBD</scp> ) 2018 guidelines for the management of patients with bipolar disorder (2018) · cites this paper as [324]
The Discussion reports that continuing antidepressants was associated with more mood episodes in rapid-cycling bipolar disorder and that concurrent mood stabilizers did not protect against worsening, at least for depressive episodes. The Methods include bipolar I, II, and NOS patients; the paper does not establish this finding specifically for rapid-cycling bipolar I patients. (LLM, conf=0.84)
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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)
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 184
- Pages
- 318-321
- ISSN
- 0165-0327 (ISSN-L)
- 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
- 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 › 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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