Predictors of switch from depression to mania in bipolar disorder

• Manic switch is a primary issue when treating bipolar depression.
• Concomitant manic symptoms and panic attacks are the strongest risk factors.
• Antidepressant treatment may not represent a primary risk factor.
• In low risk cases, younger age, past treatments or suicide attempts may be relevant.

Manic switch is a relevant issue when treating bipolar depression. Some risk factors have been suggested, but unequivocal findings are lacking. We therefore investigated predictors of switch from depression to mania in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) sample. Manic switch was defined as a depressive episode followed by a (hypo)manic or mixed episode within the following 12 weeks. We assessed possible predictors of switch using generalized linear mixed models (GLMM).8403 episodes without switch and 512 episodes with switch (1720 subjects) were included in the analysis. Several baseline variables were associated with a higher risk of switch. They were younger age, previous history of: rapid cycling, severe manic symptoms, suicide attempts, amphetamine use and some pharmacological and psychotherapeutic treatments. During the current depressive episode, the identified risk factors were: any possible mood elevation, multiple mania-associated symptoms with at least moderate severity, and comorbid panic attacks.In conclusion, our study suggests that both characteristics of the disease history and clinical features of the current depressive episode may be risk factors for manic switch.