Pharmacotherapy of bipolar mixed states


  • SK is a consultant for AstraZeneca, Eli Lilly & Co. LTY is a consultant for Eli Lilly & Co., AstraZeneca, Pfizer, Bristol-Myers Squibb. PB has received grant support from Jannsen-Cilag, AstraZeneca and is a consultant for Jannsen-Cilag, AstraZeneca, Eli Lilly & Co., GlaxoSmithKline.

Stephanie Krüger, MD, Klinik für Psychiatrie, Universitäts-Klinik Care-Gustav Carus, Dresden Fetscheist. 74, 01307 Dresden, Germany. Fax: 0351 458 5829;


Objective:  Mixed episodes comprise up to 40% of acute bipolar admissions. They are difficult-to-treat, complex clinical pictures. This review provides an overview of the available literature on the pharmacotherapy of manic-depressive mixed states and suggests treatment options.

Method:  Literature was identified by searches in Medline, Embase and the Cochrane Controlled Trials Register. Studies were considered relevant if they contained the keywords mixed mania, mixed state(s), mixed episode(s), treatment, therapy, study or trial.

Results:  Overall, there were very few double-blind, placebo-controlled studies specifically designed to treat manic-depressive mixed states. Rather, patients with mixed states comprised a sub-group of the examined patient cohorts. Nevertheless, the data show that acute mixed states do not respond favourably to lithium. Instead, valproate and olanzapine are drugs of first choice. Carbamazepine may play a role in the prevention of mixed states. Antidepressants should be avoided, because they may worsen intraepisodic mood lability. Lamotrigine may be useful in treating mixed states with predominantly depressive symptoms.

Conclusions:  More treatment studies specifically designed to treat the complex clinical picture of mixed states are clearly needed. Current treatment recommendations for clinical practice based on the available literature can only target select aspects of these episodes.