A new study investigates the links between antidepressant medication and the eventual onset of manic episodes and bipolar disorder.

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Antidepressant drugs have well-known side effects. Could mania be the latest to join the list?

Despite the steady growth of depression in America and beyond, the treatment for this, the most common psychological disorder in the Western world, still has much room for improvement.

Antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs), certainly are successful. They have made vast improvements to depressed patients’ lives.

But, as use of antidepressants creeps up and up, so does the evidence for negative long-term effects.

Current antidepressants cause a variety of immediate side effects. Among the most troublesome impacts of SSRIs (one of the most common antidepressant classes) are sexual dysfunction, weight gain and sleep disturbance.

A recent study, published in BMJ Open, uses retrospective data from more than 21,000 anonymized patients under treatment for major depression from 2006-2013. The research team set out to investigate another, more subtle and gradual side effect of antidepressants that is currently gaining evidence.

Various studies, over the past few years, have demonstrated an increase in the incidence of manic episodes and bipolar disorder linked to antidepressant usage.

A recent meta-analysis, combining the results of multiple studies, found that 12.5% of depressed patients taking antidepressants eventually displayed manic symptoms.

Another retrospective study, looking at 6 years worth of data, found a prevalence rate of the so-called manic/hypomanic switch of 13.1%.

On the other hand, not all studies have found such convincing results; some that did find a link between antidepressants, mania and bipolar were primarily looking at other parameters and found this “manic switch” relationship as an aside. There is certainly room for further investigation.

The current study, headed up by Dr. Rashmi Patel at the Department of Psychosis Studies, King’s College, London, looked into the health care records of 21,000 adults in receipt of treatment for major depression.

The results did indeed show an increased risk of mania and bipolar disorder in the patients taking antidepressants.

The team found that the overall yearly risk of a new diagnosis of mania and bipolar disorder was 1.1%. However, the patients prescribed antidepressant treatments had an increased risk of a subsequent diagnosis of bipolar disorder and/or mania. The yearly risk for this ranged from 1.3% to 1.9%.

This effect was most pronounced for SSRIs and venlafaxine, which yielded a 34-35% increase in the risk of receiving a diagnosis of either bipolar or mania. Even after controlling for potentially confounding variables, including age and gender, the results remained significant.

The authors are clear about the investigation’s limitations. This is an observational study and conclusions cannot be drawn about cause and effect.

It is not yet clear whether the antidepressant drugs cause the mania and bipolar, or whether they simply trigger a disorder that is already lying dormant. Despite the report’s shortfalls, the authors stand by the results:

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.”

Predicting a future manic episode is not, of course, an exact science, but there are clues in patient history that might be better used. A family history of mania or bipolar, a psychotic phase at an early age, problems with drugs or alcohol or unresponsive depression could all signal a natural propensity for the manic end of the spectrum.

The authors end with a note of caution: antidepressants are safe. It is essential that anyone taking depression medication continues as prescribed. Stopping medication is of much greater risk to psychological health than the potential future risk of bipolar or mania.

Medical News Today recently looked at the increasing use of ketamine as an alternative in the treatment of depression.