Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study

Objectives: To investigate the association between antidepressant therapy and the later onset of mania/ bipolar disorder. Design: Retrospective cohort study using an anonymised electronic health record case register. Setting: South London and Maudsley National Health Service (NHS) Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK. Participants: 21 012 adults presenting to SLaM between 1 April 2006 and 31 March 2013 with unipolar depression. Exposure: Prior antidepressant therapy recorded in electronic health records. Main outcome measure: Time to subsequent diagnosis of mania or bipolar disorder from date of diagnosis of unipolar depression, censored at 31 March 2014. Methods: Multivariable Cox regression analysis with age and gender as covariates. Results: The overall incidence rate of mania/bipolar disorder was 10.9 per 1000 person-years. The peak incidence of mania/bipolar disorder incidence was seen in patients aged between 26 and 35 years (12.3 per 1000 person-years). Prior antidepressant treatment was associated with an increased incidence of mania/ bipolar disorder ranging from 13.1 to 19.1 per 1000 person-years. Multivariable analysis indicated a significant association with selective serotonin reuptake inhibitors (HR 1.34, 95% CI 1.18 to 1.52) and venlafaxine (1.35, 1.07 to 1.70). Conclusions: In people with unipolar depression, antidepressant treatment is associated with an increased risk of subsequent mania/bipolar disorder. These findings highlight the importance of considering risk factors for mania when treating people with depression.