Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline
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Background: Few studies have examined the relative risks of switching into hypomania or mania associated with second-generation antidepressant drugs in bipolar depression. Aims: To examine the relative acute effects of bupropion, sertraline and venlafaxine as adjuncts to mood stabilisers. Method: In a 10-week trial, participants receiving out-patient treatment for bipolar disorder (stratified for rapid cycling) were randomly treated with a flexible dose of one of the antidepressants, or their respective matching placebos, as adjuncts to mood stabilisers. Results: A total of 174 adults with bipolar disorder I, II or not otherwise specified, currently in the depressed phase, were included. All three antidepressants were associated with a similar range of acute response (49–53%) and remission (34–41%). There was a significantly increased risk of switches into hypomania or mania in participants treated with venlafaxine compared with bupropion or sertraline. Conclusions: More caution appears indicated in the use of venlafaxine rather than bupropion or sertraline in the adjunctive treatment of bipolar depression, especially if there is a prior history of rapid cycling.
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SNRIs and MAOIs have a higher propensity than other antidepressants to induce manic switch and cause mood destabilization.
“Other classes of antidepressants such as serotonin‐ norepinephrine reuptake inhibitors [SNRIs] and monoamine oxidase inhibitors [MAOIs] could be used adjunctively but clinicians need to ensure adequate anti‐manic prophylaxis in such situations, as SNRIs and MAOIs have a higher propensity than other antidepressants to induce manic switch and cause mood destabilization (level 2).276, 277, 278”
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 [276]
The 'Overall response and switch rates on antidepressant augmentation' section reports a greater switch risk with venlafaxine than with bupropion or sertraline, largely driven by patients with rapid-cycling disorder. The paper does not establish that SNRIs as a class have higher risk, and the passages do not address MAOIs or show that either class causes mood destabilization. Page numbers were not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAntidepressant monotherapy can induce hypomania and rapid cycling.
“Antidepressant monotherapy can induce hypomania and rapid cycling (3).”
From Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial (2018) · cites this paper as [3]
The Clinical and research implications section reports switches into hypomania or mania during antidepressant treatment, particularly with venlafaxine. But the Method section says the antidepressants were added to mood stabilisers, not used as monotherapy, and the Rapid cycling section treats rapid cycling as an existing patient status rather than an outcome induced by treatment. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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References 39 · Cited by 350
- Authors
- Post, R. M., Altshuler, L. L., Leverich, G. S., Frye, M. A., Nolen, W. A., Kupka, R. W., Suppes, T., McElroy, S., Keck, P. E., Denicoff, K. D., Grunze, H., Walden, J., Kitchen, C. M. R., & Mintz, J.
- Affiliations
- National Institute of Mental Health (US)
- University of California, Los Angeles (US)
- University Medical Center Groningen (NL)
- The University of Texas Southwestern Medical Center (US)
- University of Cincinnati (US)
- Ludwig-Maximilians-Universität München (DE)
- TU Bergakademie Freiberg (DE)
- Corresponding author
- Post, R. M.
- Venue
- British Journal of Psychiatry
- Publisher
- Royal College of Psychiatrists
- Published
- 2006-08
- Volume
- 189
- Issue
- 2
- Pages
- 124-131
- ISSN
- 0007-1250 (ISSN-L)
- 1472-1465
- OpenAlex
- W2121798700
- Semantic Scholar
- 54757d9cf04619d1388743c207ccaf4b2c3431dc
- Cited by
- 350
- References
- 39
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 11 · 2021: 34 · 2020: 10 · 2019: 7 · 2018: 10 · 2017: 11 · 2016: 18 · 2015: 20 · 2014: 16 · 2013: 19 · 2012: 27
- FWCI
- 16.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The British Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Pfizer
- GlaxoSmithKline
- Stanley Medical Research Institute
- National Institute of Mental Health
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- bipolar depression, venlafaxine, bupropion, sertraline, manic switch, rapid cycling bipolar disorder, mood stabilizers, antidepressant safety
- MeSH terms
- Venlafaxine Hydrochloride, Adjuvants, Pharmaceutic, Adult, Affect, Antidepressive Agents, Bipolar Disorder, Cyclohexanols, Depressive Disorder, Double-Blind Method, Female, Humans, Male, Risk Factors, Severity of Illness Index, Bupropion, Treatment Outcome, Antidepressive Agents, Second-Generation, Sertraline
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