Antidepressants may increase later onset of mania, bipolar




People diagnosed with unipolar depression have a higher chance of developing mania or bipolar disorder if they’ve previously been treated with antidepressants, a new study shows (BMJ Open. 2015 Dec 15. doi: 10.1136/bmjopen-2015-008341).

“Our findings demonstrate a significant association between antidepressant therapy in patients with unipolar depression and an increased incidence of mania,” Dr. Rashmi Patel of King’s College, London, and his associates reported in the study. Moreover, the association remains significant after adjusting for both age and gender, they wrote.


Dr. Patel and his associates conducted a retrospective cohort study on 21,012 individuals aged 16 to 65 years – all of whom were diagnosed with depression and had no previous diagnosis of mania or bipolar disorder between April 1, 2006, and March 31, 2013 – from the South London and Maudsley National Health Service Foundation Trust. Clinical data on subjects’ medical history, mental state examinations, diagnostic formulations, and management plans were collected. Subjects also were classified as having had “prior antidepressant therapy” if there was “documentation of antidepressant treatment prior to the date of diagnosis of depression.” Follow-ups occurred through March 31, 2014, and the primary outcome was a diagnosis of mania or bipolar disorder during that period.

Results showed an incidence rate of 10.9 per 1,000 person-years of mania or bipolar disorder across the entire study population. The lowest incidence, 8.3 per 1,000 person-years, was in the 56-65 years age cohort, while those in the 26-35 years age cohort had the highest incidence rate – 12.3 per 1,000 person-years (P = .004).

Subjects with prior antidepressant use saw significant increases in incidence rates of mania or bipolar disorder, depending on which antidepressant they were taking. Those on tricyclics (4.7% of subjects with previous antidepressant treatment) had a 13.1 per 1,000 person-years incidence rate, while those taking trazodone (0.8%) had a 19.1 per 1,000 person-years incidence rate (P = .09 and P = .03, respectively). The most commonly used antidepressants were selective serotonin reuptake inhibitors (35.5%), which yielded an incidence rate of 13.2 per 1,000 person-years.

“The association of antidepressant therapy with mania demonstrated in the present and previous studies highlights the importance of considering whether an individual who presents with depression could be at risk of future episodes of mania,” the authors concluded. They concluded that the findings reinforce the “ongoing need to develop better ways to predict future risk of mania in people with no prior history of bipolar disorder who present with an episode of depression.”

The study was supported by the U.K. Medical Research Council Clinical Research Training Fellowship. Neither Dr. Patel nor his associates reported relevant financial disclosures.

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