Clinical decision making in the treatment of mixed states

Abstract

Objectives. We reviewed the treatment of bipolar mixed states using efficacy data of licensed and non-licensed physical or pharmacological treatments. Methods. We conducted a literature search to identify published studies reporting data on mixed states. Grading was done using an in-house level of evidence and we compared the efficacy with treatment recommendations of mixed states in current bipolar disorder guidelines. Results. A total of 133 studies reported data on mixed states, and seven guidelines differentiate the acute treatment of mixed states from pure states. The strongest evidence in treating co-occurring manic and depressive symptoms was for monotherapy with aripiprazole, asenapine, extended release carbamazepine, valproate, olanzapine, and ziprasidone. Aripiprazole was recommended in three guidelines, asenapine in one, and carbamazepine and ziprasidone in two. As adjunctive treatment, the strongest evidence of efficacy was for olanzapine plus lithium or valproate. For maintenance, there is evidence for the efficacy of monotherapy with valproate, olanzapine, and quetiapine. In the six guidelines valproate or olanzapine are first line monotherapy options; one recommends quetiapine. Recommended add-on treatments are lithium or valproate plus quetiapine. Conclusions. There is a lack of studies designed to address the efficacy of medications in mixed affective symptoms. Guidelines do not fully reflect the current evidences.

Key words::

• mixed states
• bipolar disorder
• clinical management
• pharmacotherapy
• clinical guidelines

Acknowledgements

We thank Dr Mònica Gratacòs from CHC-Europe, who provided valuable editorial support funded by H. Lundbeck A/S.

Funding body agreement

Funding for this manuscript was provided by H. Lundbeck A/S.

Statement of Interest

Dr. Heinz Grunze received grants/research support, consulting fees and honoraria within the last 3 years from Astra Zeneca, BMS, Desitin, Eli Lilly, Gedeon-Richter, Hoffmann-LaRoche, Janssen-Cilag, Lundbeck, Merck, Otsuka, Sanofi-Aventis, Servier, Sepracor, and UBC.

Dr. Jean-Michel Azorin has undertaken consultancy work for Lilly, Aventis, Janssen, Lundbeck, Astra Zeneca, and BMS. He has received honoraria and hospitality from Lilly, Janssen, Lundbeck, BMS, Pfizer, and Novartis in relation to conference presentations.