Mania and bipolar disorder may be adverse effects of antidepressant therapy — venlafaxine and selective serotonin reuptake inhibitors (SSRIs) in particular — according to a new study published in BMJ Open.

Prior studies have suggested this same effect yet were unable to determine if antidepressants cause acute symptoms of hypomania. These studies also considered several outcomes, not just the goal of identifying the rate of mania or hypomania that occurs from certain antidepressants. The present study, then, focuses on this incidence rate with a "real-world sample" of men and women aged 16 to 68 already diagnosed with depression.

Participants were all receiving mental health care from the South London and Maudsley National Health Service Foundation Trust between April 2006 and the end of March 2013. Each had been diagnosed with depression, but had no prior diagnosis of mania or bipolar disorder.

Researchers reviewed their electronic health records, which detail patients' medical history, mental state examination, and treatment plans, in order to determine any subsequent diagnoses of mania or bipolar disorder. Then, they extracted data on prior antidepressant use and subsequent diagnoses; prior use was defined as any antidepressants taken before a formal diagnosis.

The antidepressants included in the study were monomine-oxidase inhibitors; mirtazapine; SSRIs; TCAs; trazodone; venlafaxine; duloxetine; agomelatine and reboxetine.

Of the 21,012 records reviewed, 994 were diagnosed with mania or bipolar disorder during follow-up. The "peak diagnosis" was among patients aged 26 to 35 who were more commonly prescribed SSRIs, mirtazapine, venlafaxine, and tricyclics; greater risk was associated with SSRIs and venlafaxine.

Prior antidepressant use was associated with a heightened risk of a subsequent diagnosis of mania or bipolar disorder, a yearly risk that ranged from 1.3 to 1.9 percent.

"Our findings demonstrate a significant association between antidepressant therapy in patients with unipolar depression and an increased incidence of mania," the researchers wrote. "This association remained significant after adjusting for age and gender."

That said, the estimates found in this study were lower than previous studies have seen. One reason for the discrepancy, researchers pointed out, may be because the sample size was drawn from patients presenting to secondary mental health, having already receiving antidepressant therapy from their primary provider.

There are study limitations outside of this, as well. The findings are based on observational data, "so it’s not possible to infer an aetiological association between antidepressant exposure and subsequent mania/bipolar disorder." Using this kind of data also means researchers can’t draw conclusions about cause and effect — more research needs to be done.

"Despite these limitations, we have demonstrated an association between antidepressant therapy and subsequent mania/bipolar disorder using a large data set of clinical data that is prospectively recorded and representative of everyday clinical practice in secondary mental healthcare," researchers said. "Our findings are therefore generalizable to people receiving standard antidepressant therapy for depression and in keeping with previous studies drawn from observational and interventional research studies."

Most importantly, researchers said this study "highlights an ongoing need to develop better ways to predict future risk of mania in people with no prior history of bipolar."

Source: Patel R, Reiss P, Shetty H, et al. Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study. BMJ Open. 2015.