Review: Combination therapy with non-clozapine atypical antipsychotic medication: a review of current evidence.

Use of combined antipsychotics for patients with treatment-resistant/refractory schizophrenia is common practice in psychiatry. The objective of this paper is to review the current literature on combining non-clozapine atypical antipsychotics as well as discussing the theoretical benefits and risks, and summarizing the implications for clinical practice. We found in cases of treatment-resistant schizophrenia, where clozapine is deemed inappropriate, combination therapy with non-clozapine atypical antipsychotics is a strategy worthy of consideration. Combinations using olanzapine with either amisulpride or risperidone--or quetiapine with risperidone--in theory act on different receptor profiles and in the limited data available have shown improvement in symptoms, been used most frequently, and on balance have more data on safety. Initial case reports suggest that aripiprazole combined with non-clozapine atypicals may worsen psychosis. The current literature, however, has significant limitations. For this reason, due to the lack of data on safety, caution is recommended. There needs to be further well-designed studies with the aim to specifically investigate the effects of combination therapy to allow the clinician to better balance the risks and benefits (both clinical and economical) of treatment.