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Reducing the Risk of Triggering Mania with the Use of Antidepressants in Bipolar Disorder

shutterstock_212693140A recent article in the American Journal of Psychiatry sheds light on the vexing challenge of treating depression in individuals who have an underlying bipolar disorder: For many people with bipolar disorder, depression occurs more frequently and damages function more severely than mania, but treating bipolar depression with antidepressants carries the risk of triggering manic symptoms.

The Risk of Switch to Mania in Patients with Bipolar Disorder during Treatment with an Antidepressant Alone and in Combination with a Mood Stabilizer
Alexander Viktorin, M.Sc.; Paul Lichtenstein, Ph.D.; Michael E. Thase, M.D.; Henrik Larsson, Ph.D.; Cecilia Lundholm, M.Sc.; Patrik K.E. Magnusson, Ph.D.; Mikael Landén, M.D., Ph.D.
Am J Psychiatry 2014;:. doi:10.1176/appi.ajp.2014.13111501

A number of previous studies suggest high rates of switching even in patients who are taking a mood stabilizer with the antidepressant, but data from this new study provide no evidence of increased risk of switching when the antidepressants are given with a mood stabilizer.
The study identified 3,420 patients in the Swedish National Registries, who were diagnosed with bipolar I disorder. This new study differs from previous, similar studies in two important ways:

  • Instead of comparing data from different participants, this study compared results from individual patients at different times — pre-treatment and post-treatment — in order to reduce confounding variables differences between participants, such as illness severity, genetic factors, or environmental variations.
  • Participants were restricted to only those diagnosed as having bipolar I. I think that this focus on just one subtype of bipolar disorder is helpful, because bipolar I and bipolar II differ and may well have different responses to medications.

The study focused on two groups — those receiving monotherapy (antidepressant only) and those receiving an antidepressant plus a mood stabilizer:

  • Antidepressant only: Surprisingly, 35 percent of the patients were on monotherapy. These patients had a nearly three times higher risk of developing mania in the first three months of treatment than in prior periods of their illness without the antidepressant.
  • Antidepressant + mood stabilizer (anti-manic medication): The participants receiving a combined treatment protocol of mood stabilizer plus an antidepressant showed no increased risk of mania in the first three months of treatment compared to a prior non-treatment period. And in the three-to-nine month period of treatment with the combination there was a decreased risk of mania.

This study teaches two important lessons:

  • Caution should be used in treating bipolar depression with antidepressants, even in people who present with only symptoms of depression (not mania).
  • Antidepressants can be used safely to treat depression in people who have bipolar I, as long as the antidepressant is combined with a so-called mood stabilizer (an anti-manic medication).

Common practice in treating depression in someone who has or is suspected of having an underlying bipolar disorder is to start treatment with lithium, which has shown some success in treating both poles of bipolar disorder — depression and mania. If the lithium is effective in treating the depression, monotherapy with lithium may continue. If the lithium is not effective by itself, then an antidepressant may be added with less risk of triggering manic symptoms than if the antidepressant were to be used alone.

Man on a bench image available from Shutterstock.

Reducing the Risk of Triggering Mania with the Use of Antidepressants in Bipolar Disorder

Candida Fink, MD

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APA Reference
Fink, C. (2014). Reducing the Risk of Triggering Mania with the Use of Antidepressants in Bipolar Disorder. Psych Central. Retrieved on August 15, 2020, from


Last updated: 4 Sep 2014
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