Antidepressant use in the treatment of bipolar disorder is controversial due the risks of affective switching and cycle acceleration. Studies of non-comorbid samples suggest that the risk can be mitigated with the use of a concomitant mood stabilizer. However, the majority of patients with bipolar disorder will experience a comorbid substance use disorder and little is known about these individuals because they are typically excluded from clinical trials. Patients entering a substance abuse treatment program who had a history of bipolar disorder were interviewed to evaluate antidepressant-induced affective switching with and without concomitant mood stabilizer. Among 41 comorbid participants, the total lifetime antidepressant-induced switch rate was 76%. The switch rate was 56% for patients taking a mood stabilizer and an antidepressant concomitantly. There was no difference between patients with bipolar I and bipolar II disorders.