Antidepressant-Induced Mania in Bipolar Patients: Identification of Risk Factors

Background: Concerns about possible risks ofswitching to mania associated with antidepressants continue tointerfere with the establishment of an optimal treatment paradigmfor bipolar depression.

Method: The response of 44 patients meetingDSM-IV criteria for bipolar disorder to naturalistic treatmentwas assessed for at least 6 weeks using the Montgomery-AsbergDepression Rating Scale and the Bech-Rafaelson Mania RatingScale. Patients who experienced a manic or hypomanic switch werecompared with those who did not on several variables includingage, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number ofprevious manic episodes, type of antidepressant therapy used(electroconvulsive therapy vs. antidepressant drugs and, moreparticularly, selective serotonin reuptake inhibitors [SSRIs]),use and type of mood stabilizers (lithium vs. anticonvulsants),and temperament of the patient, assessed during a normothymicperiod using the hyperthymia component of the SemistructuredAffective Temperament Interview.

Results: Switches to hypomania or mania occurredin 27% of all patients (N = 12) (and in 24% of the subgroup ofpatients treated with SSRIs [8/33]); 16% (N = 7) experiencedmanic episodes, and 11% (N = 5) experienced hypomanic episodes.Sex, age, diagnosis (bipolar I vs. bipolar II), and additionaltreatment did not affect the risk of switching. The incidence ofmood switches seemed not to differ between patients receiving ananticonvulsant and those receiving no mood stabilizer. Incontrast, mood switches were less frequent in patients receivinglithium (15%, 4/26) than in patients not treated with lithium(44%, 8/18; p = .04). The number of previous manic episodes didnot affect the probability of switching, whereas a high score onthe hyperthymia component of the Semistructured AffectiveTemperament Interview was associated with a greater risk ofswitching (p = .008).

Conclusion: The frequency of mood switchingassociated with acute antidepressant therapy may be reduced bylithium treatment. Particular attention should be paid topatients with a hyperthymic temperament, who have a greater riskof mood switches.