Strongest association found for SSRIs and venlafaxine

Taking certain antidepressants for depression is linked to a heightened risk of subsequent mania and bipolar disorder, reveals research published in the online journal BMJ Open.

The strongest association seemed to be for serotonin reuptake inhibitors, or SSRIs for short, and the dual action antidepressant venlafaxine, the analysis indicated.

The researchers base their findings on the anonymised medical records of more than 21,000 adults in receipt of treatment for major (unipolar) depression between 2006 and 2013 at a large provider of inpatient and community mental healthcare in London.

The research team looked at subsequent diagnoses of bipolar disorder or mania following an original diagnosis of unipolar depression, so-called because it lacks the ‘highs’ typical of bipolar disorder.

The analysis revealed that the overall yearly risk of a new diagnosis of mania and bipolar disorder between 2006 and 2013 was 1.1% (10.9/1000 patient years).

The peak age for diagnosis was seen among patients aged 26 to 35, among whom the yearly risk was 1.2% (12.3/1000 patient years).

The most commonly prescribed antidepressants were SSRIs (35.5%); mirtazapine (9.4%); venlafaxine (5.6%) and tricyclics (4.7%).

Previous treatment with certain antidepressants was associated with a heightened risk of a subsequent diagnosis of bipolar disorder and/or mania, the yearly risk of which ranged from 1.3% to 1.9% (13.1 to 19.1/1000 patient years).

Further analysis revealed that this heightened risk was particularly associated with treatment with SSRIs and venlafaxine. These drugs were associated with a 34-35% increased risk of being diagnosed with bipolar disorder and/or mania.

These findings held true even after taking account of potentially influential factors.

This is an observational study so no firm conclusions can be drawn about cause and effect, and the researchers point out that their findings may be explained by latent bipolar disorder rather than any effects of drug treatment. Furthermore, they were unable to obtain information on important risk factors.

“However, regardless of underlying diagnosis or aetiology 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 high risk of future episodes of mania,” say the researchers.

Pertinent risk factors include a family history of bipolar disorder, a depressive episode with psychotic symptoms, young age at first diagnosis of depression, and depression that is unresponsive to treatment.

“Our findings also highlight an 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,” they write.

In an accompanying videocast, the researchers highlight that the absolute risk of developing bipolar disorder is low and antidepressants are safe and effective treatments for depression and anxiety. Patients should not stop their treatment suddenly as this may result in withdrawal symptoms, they advise.

A video abstract for this manuscript is available to view here: https://www.youtube.com/watch?v=LPaiMOog2ss