Journal & Summary

Title: Antipsychotic Combinations for Schizophrenia

In patients that may not have a sufficient response from initial antipsychotic tx adding a second antipsychotic medication may be considered.

Objectives of this study

  1. Examining whether antipsychotic combination is effective for treating Schizophrenia 
  2. What antipsychotic combinations is safe for treating Schizophrenia? 

Study type: Review 

Methods: A search of the Cochrane Schizophrenia Group’s register including CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials was done IN September 2010, August 2012, and January 2016.

Subjects & materials: 62 studies consisting of Randomized and Quasi-randomized controlled trials that compared antipsychotic monotherapy, and combination therapies for Schizophrenia and /or Schizophrenia like psychoses. 


– 31 of 62 studies included compared clozapine monotherapy to combination therapy 

– It was believed that combination therapy may be superior in bringing about clinical response (RR 0.73 CI 0.64 – 0.83; participants = 2398; studies = 29; very low-quality evidence)

– Some of the positive findings from the combination therapies were believed to be due to the inclusion of clozapine in most combination groups 

– The subgroup analyses with atypical antipsychotics in both monotherapy and combination groups did not show a difference between the 2 interventions 

– One study showed that antipsychotics combination might decrease the risk of relapse 


– They report that antipsychotic combination therapy during these short-term trials (limitation) showed improved clinical response in patients. This evidence although considered low quality evidence shows that combination of antipsychotics may be more effective for tx Schizophrenia. 

– Combinations with clozapine particularly and typical antipsychotics were found to be effective. 

– in terms of hospital admission there was no difference between combination or monotherapy.

Limitations:  Risk of bias was considered moderate -high (due to things like selective reporting and unclear allocation concealment)


  1. Ortiz-Orendain J, Castiello-de Obeso S, Colunga-Lozano L, Hu Y, Maayan N, Adams CE. Antipsychotic combinations for schizophrenia. Cochrane Database of Systematic Reviews 2017, Issue 6. Art. No.: CD009005. DOI: 10.1002/14651858.CD009005.pub2