Bipolar disorder, antidepressants and induction of hypomania or mania. A systematic review

Objective: The literature cautions against the induction of (hypo)mania owing to the use of antidepressants in bipolar disorder. Objectives of this review are to examine: (1) the evidence for this assumption; (2) underlying risk factors;, and (3) the extent to which a mood stabilizer may be protective. Method: A systematic literature review was conducted. Results: Thirteen relevant studies were included. All of them had methodological shortcomings. Overall, there is no strong evidence that use of antidepressants in bipolar disorder increases the risk of (hypo)mania. Possible, although unreplicated, risk factors are: a short allele of the promoter region of the serotonin transporter gene SCL6A4, substance abuse or dependence, multiple antidepressant trials, lower number of previous manias, less delusions during illness, depressive polarity at illness onset, and rapid cycling that has, however, been contradicted by another study. Subtype of bipolar disorder (I or II) has been considered in four studies, with conflicting results. Mood stabilizers are possibly protective. Conclusion: There is an urgent need for adequate studies of sufficient size. For the time being, treatment of bipolar depression may best be based on the results of the life chart of the individual patient keeping in mind the risk factors found until now.