A retrospective cohort study of 21,012 adults to investigate which antidepressants pose the greatest risk of developing mania

Rashmi Patel, Peter Reiss, Hitesh Shetty, Matthew Broadbent, Robert James Stewart, Philip McGuire, Matthew John Taylor

Research output: Contribution to journalPoster abstractpeer-review

36 Citations (Scopus)


Purpose: First episode bipolar disorder may be misrecognised and inappropriately treated with antidepressants which may increase risk of developing mania. However, the extent to which this depends on what type of antidepressant is prescribed remains unclear. We investigated the association between different classes of antidepressants and subsequent onset of mania in a large sample of patients receiving mental healthcare for depression.

Materials and Methods: Data on prior antidepressant therapy were extracted from 21,012 adults receiving care for depression from the South London and Maudsley NHS Foundation Trust (SLaM) using the Clinical Record Interactive Search tool (CRIS). Multivariable Cox regression analysis (with age and gender as covariates) was used to investigate the association of antidepressant therapy with risk of developing mania.

Results: 91,110 person-years of follow-up data were analysed (mean follow-up: 4.3 years). The overall incidence rate of mania was 10.9 per 1000 person-years. The peak incidence of mania was seen in patients aged between 26 and 35 years (12.3 per 1000 person-years). The most frequently prescribed antidepressants were SSRIs (35.5%), mirtazapine (9.4%), venlafaxine (5.6%) and TCAs (4.7%). Prior antidepressant treatment was associated with an increased incidence of mania ranging from 13.1 to 19.1 per 1000 person-years. Multivariable analysis indicated a significant association with SSRIs (Hazard ratio 1.34, 95% CI 1.18-1.52) and venlafaxine (1.35, 1.07-1.70).

Conclusion: Antidepressant treatment is associated with an increased risk of subsequent mania. These findings highlight the importance of considering the possibility of an emerging bipolar disorder when treating people with antidepressants.
Original languageEnglish
Article numbereip.12397
Pages (from-to)178
Number of pages1
JournalEarly Intervention in Psychiatry
Issue numberS1
Publication statusPublished - 3 Oct 2016


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