BACKGROUND

While most guidelines recommend monotherapy with second-generation antipsychotics (SGA) in schizophrenia, the combined application of multiple psychotropic agents is very common, especially in treatment-refractory cases.

METHODS

This review summarizes the evidence of combined antipsychotic treatment strategies and the augmentation of antipsychotics with mood stabilizers, antidepressants and experimental substances, based on publications accessible in public databases (Medline/Ovid, Google, http://www.clinicaltrials.gov) up to October 2009.

RESULTS

Polypharmacy aims to address several aspects of treatment resistance and side effects of antipsychotics. Some evidence supports the augmentation of antipsychotics with 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, cognitive re-mediation seems most promising as no pharmacological add-on strategy has gained convincing evidence so far. Acute dystonic movements should be treated with anticholinergic agents while agitation and anxiety might respond to short-term application of benzodiazepines. Treatment-resistant positive and/or negative symptoms should primarily lead to clozapine monotherapy; the add-on of a second SGA may be considered in single cases.

CONCLUSIONS

In general, rigorous data on combination therapy in schizophrenia are rare, and further randomized controlled trials (RCT), naturalistic and head-to-head-studies are necessary.