The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
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 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 ( CANMAT ) and International Society for Bipolar Disorders ( ISBD ) 2018 guidelines for the management of patients with bipolar disorder (2018) · cites this paper as [324]
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Yatham, L. N., & Malhi, G. S. (2011) · Oxford University Press eBooks · doi:10.1093/med/9780199562305.001.0001 · Cited by 3,515
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Self-citationFundamentals of Clinical Trials
Friedman, L. M., Furberg, C. D., DeMets, D. L., Reboussin, D. M., & Granger, C. B. (2015) · doi:10.1007/978-3-319-18539-2 · Cited by 2,237
Fundamentals of Clinical Trials
Friedman, L. M., Furberg, C. D., & DeMets, D. L. (1998) · doi:10.1007/978-1-4757-2915-3 · Cited by 873
Pacchiarotti, I., Bond, D. J., Baldessarini, R. J., Nolen, W. A., Grunze, H., Licht, R. W., Post, R. M., Berk, M., Goodwin, G. M., Sachs, G. S., et al. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.13020185 · Cited by 770
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Antidepressant Treatment in Bipolar Versus Unipolar Depression
Ghaemi, S. N., Rosenquist, K. J., Ko, J. Y., Baldassano, C. F., Kontos, N. J., & Baldessarini, R. J. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.1.163 · Cited by 271
Self-citationThe Long-term Course of Rapid-Cycling Bipolar Disorder
Coryell, W. H., Solomon, D., Turvey, C., Keller, M. B., Leon, A. C., Endicott, J., Schettler, P. J., Judd, L. L., & Mueller, T. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.9.914 · Cited by 251
The Prospective Course of Rapid-Cycling Bipolar Disorder: Findings From the STEP-BD
Schneck, C. D., Miklowitz, D. J., Miyahara, S., Araga, M., Wisniewski, S. R., Gyulai, L., Allen, M. H., Thase, M. E., & Sachs, G. S. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2007.05081484 · Cited by 186
Baldessarini, R. J., Henk, H. J., Sklar, A., Chang, J. P., & Leahy, L. (2008) · Psychiatric Services · doi:10.1176/ps.2008.59.10.1175 · Cited by 179
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Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., Sharma, V., Goldstein, B. I., Rej, S., Beaulieu, S., et al. (2018) · Bipolar Disorders · doi:10.1111/bdi.12609 · Cited by 1,852
“Several methodological shortcomings likely resulted in the studies underestimating the drug’s effect, including 1) a slow titration which resulted in subjects being on the target dose for a short time, 2) a target dose lower than that often used in clinical practice and in successful maintenance studies (255, 324), an…”
BackgroundInfluentialMalhi, G. S., Bassett, D., Boyce, P., Bryant, R., Fitzgerald, P. B., Fritz, K., Hopwood, M., Lyndon, B., Mulder, R., Murray, G., et al. (2015) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867415617657 · Cited by 842
“…antidepressants in patients with rapid-cycling bipolar disorder leads to a threefold increase in mood episodes during the first year of follow up (El-Mallakh et al., 2015) whereas continuation of antidepressant monotherapy in BD II provides prophylaxis with only minimal risk of switching…”
BackgroundResultFountoulakis, K. Ν., Yatham, L. N., Grunze, H., Vieta, E., Young, A. H., Blier, P., Kasper, S. F., & Moeller, H. J. (2016) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw100 · Cited by 117
Sackeim, H. A., Aaronson, S. T., Bunker, M. T., Conway, C. R., Demitrack, M. A., George, M. S., Prudic, J., Thase, M. E., & Rush, A. J. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.03.021 · Cited by 109
Depression Preceding Diagnosis of Bipolar Disorder
O’Donovan, C., & Alda, M. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00500 · Cited by 87
Metadata
- 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 (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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