Association between antidepressant resistance in unipolar depression and subsequent bipolar disorder: cohort study
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Background: People with major depressive disorder who fail to respond to adequate trials of antidepressant treatment may harbour hidden bipolar disorder. Aims: We aimed to compare the rates of a change in diagnosis to bipolar disorder among people with major depressive disorder with stratified responses to antidepressants during an 8-year follow-up period. Method: Information on individuals with major depressive disorder identified during 2000 (cohort 2000, n = 1485) and 2003 (cohort 2003, n = 2459) were collected from a nationally representative cohort of 1 000 000 health service users in Taiwan. Participants responding well to antidepressants were compared with those showing poor responses to adequate trials of antidepressants. Results: In 7.6–12.1% of those with a diagnosis of unipolar major depressive disorder this diagnosis was subsequently changed to bipolar disorder, with a mean time to change of 1.89–2.98 years. Difficult-to-treat participants presented higher rates of change to a bipolar diagnosis (25.6% in cohort 2000; 26.6% in cohort 2003) than easy-to-treat participants (8.8–8.9% in cohort 2000; 6.8–8.6% in cohort 2003; P <0.0001). Regression analysis showed that the variable most strongly associated with the change in diagnosis was antidepressant use history. The difficult-to-treat participants were associated most with diagnostic changing (cohort 2000: odds ratio (OR) = 1.88 (95% CI 1.12–3.16); cohort 2003: OR = 4.94 (95% CI 2.81–8.68)). Conclusions: This is the first large-scale study to report an association between antidepressant response history and subsequent change in diagnosis from major depressive disorder to bipolar disorder. Our findings support the view that a history of poor response to antidepressants in unipolar depression could be a useful predictor for bipolar diathesis.
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Individuals prescribed multiple failed antidepressant trials (i.e., TRD) have a much greater likelihood of an underlying diagnosis of bipolar disorder as compared to persons prescribed a single antidepressant trial.
“Indeed, it is reported that individuals prescribed multiple failed antidepressant trials (i.e., TRD) have a much greater likelihood of an underlying diagnosis of bipolar disorder as compared to persons prescribed a single antidepressant trial 157 .”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [157]
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- Correa R, Akiskal H, Gilmer W, Nierenberg AA, Trivedi M, Zisook S. Is unrecognized bipolar disorder a frequent contributor to apparent treatment resistant depression? J Affect Disord 2010; 126: 10-8.
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Self-citation
- Authors
- Li, C.-T., Bai, Y.-M., Huang, Y.-L., Chen, Y.-S., Chen, T.-J., Cheng, J.-Y., & Su, T.-P.
- Affiliations
- Taipei Veterans General Hospital (TW)
- National Yang Ming University (TW)
- Corresponding author
- Su, Tung-Ping
- Venue
- British Journal of Psychiatry
- Publisher
- Royal College of Psychiatrists
- Published
- 2012-01
- Volume
- 200
- Issue
- 1
- Pages
- 45-51
- ISSN
- 0007-1250 (ISSN-L)
- 1472-1465
- OpenAlex
- W2164793282
- Cited by
- 177
- References
- 24
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 10 · 2023: 10 · 2022: 10 · 2021: 9 · 2020: 9 · 2019: 9 · 2018: 12 · 2017: 13 · 2016: 13 · 2015: 12 · 2014: 17 · 2013: 17 · 2012: 14
- FWCI
- 10.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The British Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health Research Institutes
- Taipei Veterans General Hospital
- 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
- antidepressant resistance, unipolar major depression, bipolar disorder, antidepressant response, diagnostic change, treatment-resistant depression
- MeSH terms
- Adult, Antidepressive Agents, Anxiety Disorders, Bipolar Disorder, Major Depressive Disorder, Diagnosis, Differential, Disease Susceptibility, Epidemiologic Methods, Female, Humans, Male, Middle Aged, Taiwan, Outcome Assessment, Health Care, Substance-Related Disorders, International Classification of Diseases, Depressive Disorder, Treatment-Resistant
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