The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders
Open accessAbstract
OBJECTIVE: The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. METHOD: An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. RESULTS: There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. CONCLUSIONS: Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.
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For patients with bipolar disorder I, antimanic therapy prevents (hypo)manic episodes and avoids mood induction effects during BLT.
“For patients with BD I, antimanic therapy is indicated during BLT and at least 2–4 weeks prior to initiating BLT (Pacchiarotti et al. 2013), to prevent (hypo)manic episodes and to avoid mood induction effects.”
From Light therapy for bipolar disorders: Clinical recommendations from the international society for bipolar disorders (ISBD) Chronobiology and Chronotherapy Task Force (2025) · cites this paper as Pacchiarotti et al. 2013
The Consensus Statements recommend mood-stabilizing treatment alongside antidepressants for patients with bipolar I disorder, but say its ability to prevent treatment-associated mood switching is unproven. The cited paper does not address bright light therapy (BLT) or recommend starting antimanic therapy 2–4 weeks before it. The Results > Safety section likewise discusses switching during antidepressant treatment, not BLT. (LLM, conf=0.88)
Experimental — accuracy not yet measuredBupropion might occasionally induce treatment emergent affective switches, albeit with lower probability than several other antidepressants.
“Bupropion might occasionally induce treatment emergent affective switches, albeit with lower probability than several other antidepressants (82).”
From The detrimental effects of smoking on the course and outcome in adults with bipolar disorder—A narrative review (2023) · cites this paper as [82]
The Safety section reports a mood switch in one of nine bupropion-treated patients versus five of ten desipramine-treated patients, and cites a trial with a lower switch rate for bupropion than venlafaxine. It also cautions that switches may occur spontaneously and recommends “treatment-emergent affective switch” rather than “antidepressant-induced switch” to avoid implying causality. The comparative risk is supported, but the claim that bupropion induces the switches goes beyond the evidence presented. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAvailable trials do not support the efficacy of antidepressants as monotherapy in patients with BDI depression.
“Antidepressants should not be used as monotherapy in patients with BDI depression, as available trials do not support their efficacy and there are concerns about their safety in terms of mood switching (level 2 negative).260, 289, 290, 291”
There are concerns about the safety of antidepressants as monotherapy in BDI depression in terms of mood switching.
“Antidepressants should not be used as monotherapy in patients with BDI depression, as available trials do not support their efficacy and there are concerns about their safety in terms of mood switching (level 2 negative).260, 289, 290, 291”
Use of antidepressants in bipolar disorder remains controversial.
“While the use of antidepressants in BD remains controversial260, 426 and there have been no studies in older age BD; antidepressants are frequently used in this population (>40% of patients).666”
Before conducting the study, the authors chose a threshold that required ≥80% of experts to endorse a statement as Essential or Important, on the basis of ≥80% being a commonly employed threshold in mental health research and to be consistent with Delphi studies conducted by three independent ISBD Task Forces.
“Before conducting the study, we chose a threshold that required ≥ 80% of experts to endorse a statement as Essential or Important, on the basis of ≥ 80% being a commonly employed threshold in mental health research [47, 48, 49], and to be consistent with Delphi studies conducted by three independent ISBD Task Forces [50, 51, 52].”
From Essential Information About Chronobiology and Chronotherapy for the Optimal Care of People With Bipolar Disorders: An Expert Consensus (2026) · cites this paper as [50]
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Self-citation
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Research works printed but not linked: 2
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“As the recent ISBD task force report noted, “There is a striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder” (Pacchiarotti et al., 2013a).”
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Self-citationCrouse, J. J., Loblay, V., Jorm, A., Wong, T. R., de Haan, Z., Gorban, C., Shin, M., Tonini, E., Aiken, C., Alloy, L. B., et al. (2026) · Bipolar Disorders · doi:10.1111/bdi.70141 · Cited by 3 · see citing works
“…we chose a threshold that required ≥ 80% of experts to endorse a statement as Essential or Important , on the basis of ≥ 80% being a commonly employed threshold in mental health research [47–49], and to be consistent with Delphi studies conducted by three independent ISBD Task Forces [50–52].”
Self-citationCutler, A. J., Laliberté, F., Germain, G., MacKnight, S. D., Boudreau, J., Wade, S. W., & Parikh, M. (2024) · Journal of Medical Economics · doi:10.1080/13696998.2024.2419721 · Cited by 3 · see citing works
“…date. g Cariprazine treatment duration was defined as the interval between the first cariprazine dispensing and the last cariprazine dispensing. the follow-up period, which could be reflective of comorbidities or the concerningly high use of antidepressant therapies for the treatment of BP-I 4,38 .”
- Authors
- 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., Tondo, L., Findling, R. L., Youngstrom, E. A., Tohen, M., Undurraga, J., González-Pinto, A., Goldberg, J. F., Yildiz, A., Altshuler, L. L., Calabrese, J. R., Mitchell, P. B., Thase, M. E., Koukopoulos, A., Colom, F., Frye, M. A., Malhi, G. S., Fountoulakis, K. N., Vázquez, G., Perlis, R. H., Ketter, T. A., Cassidy, F., Akiskal, H., Azorin, J.-M., Valentí, M., Mazzei, D. H., Lafer, B., Kato, T., Mazzarini, L., Martínez-Aran, A., Parker, G., Souery, D., Özerdem, A., McElroy, S. L., Girardi, P., Bauer, M., Yatham, L. N., Zarate, C. A., Nierenberg, A. A., Birmaher, B., Kanba, S., El-Mallakh, R. S., Serretti, A., Rihmer, Z., Young, A. H., Kotzalidis, G. D., MacQueen, G. M., Bowden, C. L., Ghaemi, S. N., Lopez-Jaramillo, C., Rybakowski, J., Ha, K., Perugi, G., Kasper, S., Amsterdam, J. D., Hirschfeld, R. M., Kapczinski, F., & Vieta, E.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- From the Bipolar Disorders Program, Clinical Institute of Neuroscience, Hospital Clinic Barcelona, IDIBAPS (Institute of Biomedical Research August Pi i Sunyer), CIBERSAM (Center for Biomedical Research Network on Mental Health), University of Barcelona, Barcelona, Spain; Mood Disorders Centre, Department of Psychiatry, University of British Columbia, Vancouver; Department of Psychiatry, Harvard Medical School, Boston; Department of Psychiatry, University Medical Center Groningen, University of Groningen...
- ORCID
- Pacchiarotti, Isabella
- Bond, David J.
- Baldessarini, Ross J.
- Nolen, Willem A.
- Grunze, Heinz
- Licht, Rasmus W.
- Post, Robert M.
- Goodwin, Guy M.
- Tondo, Leonardo
- Findling, Robert L.
- Youngstrom, Eric A.
- Tohen, Mauricio
- Undurraga, Juan
- González-Pinto, Ana
- Goldberg, Joseph F.
- Calabrese, Joseph R.
- Mitchell, Philip B.
- Colom, Francesc
- Frye, Mark A.
- Malhi, Gin S.
- Vázquez, Gustavo
- Perlis, Roy H.
- Ketter, Terence A.
- Valentí, Marc
- Lafer, Beny
- Kato, Tadafumi
- Parker, Gordon
- Souery, Daniel
- Özerdem, Ayşegül
- McElroy, Susan L.
- Girardi, Paolo
- Bauer, Michael
- Yatham, Lakshmi N.
- Zarate, Carlos A.
- Nierenberg, Andrew A.
- Birmaher, Boris
- Serretti, Alessandro
- Young, Allan H.
- Kotzalidis, Georgios D.
- MacQueen, Glenda M.
- Ghaemi, S. Nassir
- Rybakowski, Janusz
- Ha, Kyooseob
- Perugi, Giulio
- Kasper, Siegfried
- Kapczinski, Flávio
- Vieta, Eduard
- Venue
- American Journal of Psychiatry
- Published
- 2013-11
- Volume
- 170
- Issue
- 11
- Pages
- 1249-1262
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC4091043
- OpenAlex
- W2114807890
- Cited by
- 770
- References
- 104
- Citations by year
- 2026: 43 · 2025: 47 · 2024: 42 · 2023: 47 · 2022: 46 · 2021: 53 · 2020: 60 · 2019: 65 · 2018: 59 · 2017: 67 · 2016: 67 · 2015: 89 · 2014: 80 · 2013: 4 · 2012: 1
- FWCI
- 56.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- National Institutes of Health (Z99 MH999999)
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- bipolar disorder, antidepressant use, antidepressant-induced mania, mood switching, mixed states, serotonin reuptake inhibitors, bupropion, tricyclic antidepressants, tetracyclic antidepressants, bipolar I disorder, bipolar II disorder, mood stabilizers, antidepressant safety, clinical guidelines
- MeSH terms
- Suicide Prevention, Affect, Antidepressive Agents, Bipolar Disorder, Delphi Technique, Humans, Suicide, Treatment Outcome, Advisory Committees, Consensus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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