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Antidepressant-induced mania is a well-known clinical phenomenon; patients who have rapid cycling, are female, or are taking older tricyclic antidepressants (rather than SSRIs) are reportedly at particular risk. However, in a recent meta-analysis of randomized controlled trials (RCTs), mania was not associated with antidepressant use, which suggests that the phenomenon might relate to patient characteristics screened out of RCTs. For example, substance-use disorder (SUD) is highly prevalent in bipolar patients but is an exclusion criterion in RCTs.
In a retrospective chart review of patients seen at an academic bipolar-disorder clinic over 4 years, researchers assessed whether current or past SUDs increase the risk for mania within 12 weeks …