Rapid-Cycling Bipolar Disorder

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Do Antidepressants Cause Rapid Cycling?

A particularly contentious issue regarding rapid cycling is whether it is induced by antidepressant medication.^[7] Perhaps the most convincing data to support this view were provided by a study from Wehr and colleagues^[8] of 51 patients with rapid cycling. For a subgroup of patients whose rapid cycling appeared related to antidepressant use, the investigators employed repeated on-off trials of tricyclic antidepressants to demonstrate that about 20% of the total sample had rapid cycling clearly associated with antidepressant use. Lending further support to the link between antidepressants and rapid cycling are observations that rapid mood switching has become more prevalent since antidepressant medication has come into widespread use.^[9]

However, some experts argue that the risk of antidepressant mood destabilization may have been overestimated, and that depression itself, rather than antidepressant drugs, may be responsible for periods of rapid cycling. In a 1992 prospective study from Coryell and colleagues,^[5] there was no association between antidepressant use and rapid cycling when the investigators statistically controlled for the presence of a major depressive episode.

Although questions remain about the role of antidepressants in inducing rapid-cycling bipolar disorder, US guidelines, including the American Psychiatric Association (APA) practice guidelines for the treatment of bipolar disorder,^[10] reflect the opinion that antidepressants do pose a risk for manic switching and mood destabilization -- and are therefore relatively contraindicated in patients with rapid cycling. However, because depression appears to represent a driving force behind rapid cycling,^[11] there exists a tremendous need to identify therapeutic agents with antidepressant efficacy that do not destabilize mood or induce further cycle acceleration.