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Polypharmacy in schizophrenia

Zink, Mathias; Englisch, Susanne; Meyer-Lindenberg, Andreas

Current Opinion in Psychiatry: March 2010 - Volume 23 - Issue 2 - p 103–111
doi: 10.1097/YCO.0b013e3283366427
Schizophrenia: Edited by W. Wolfgang Fleischhacker

Purpose of review Although most guidelines recommend monotherapy in schizophrenia, the combined application of multiple psychotropic agents is very common, especially in treatment-refractory cases. We review the empirical basis supporting these attempts and their relevance for clinical practice.

Recent findings Polypharmacy intends to address different aspects of treatment resistance, most importantly insufficient response of psychotic positive and negative symptoms, but also cognitive disturbances, affective comorbidity, obsessive–compulsive syndromes and side-effects of antipsychotic drugs. This review summarizes the current state of evidence of combined antipsychotic treatment strategies and the augmentation of antipsychotics with mood stabilizers, antidepressants and experimental substances.

Summary In general, rigorous data on combination therapy in schizophrenia are rare and further randomized controlled trials, naturalistic trials and head-to-head-trials are necessary. Some evidence supports a combination of antipsychotics and antidepressants for negative symptoms and comorbid major depressive episodes. The add-on of lithium and mood stabilizers lacks compelling evidence, but might be beneficial for specific subgroups. For treatment-resistant cognitive symptoms, antipsychotic medication should be combined with cognitive remediation, as no pharmacological add-on strategy has gained convincing evidence so far. Treatment-emergent positive and/or negative symptoms under clozapine monotherapy might benefit from adding a second atypical substance.

Central Institute of Mental Health, Mannheim, Germany

Correspondence to PD Dr med. Mathias Zink, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, P.O. Box 12 21 20, D-68072 Mannheim, Germany Tel: +49 621 1703 2911; fax: +49 621 1703 1205; e-mail:

© 2010 Lippincott Williams & Wilkins, Inc.