combination therapy for Schizophrenia

Doctors sometimes prescribe multiple medications to patients in an attempt to increase the effectiveness of treatment. This study calls into question the use of combination therapy for schizophrenia, showing that they are no more effective than one medication alone.


Schizophrenia is a serious mental illness that affects countless men and women each year. Antipsychotic drugs, the cornerstone of schizophrenia treatment, are limited and sometimes ineffective. This can lead doctors to prescribe combination therapies (two or more medications at the same time), in an attempt to enhance treatment effectiveness. There has been an overwhelming amount of research done to assess the effectiveness of combination therapies but the results have been mixed.

To assess a complex research question, scientists perform meta-analyses to systematically review of all valid and relevant data from existing studies. Taking this a step further, scientists from the Feinstein Institute for Medical Research performed a rigorous analysis of all published meta-analyses concerning the effectiveness of combination therapy for schizophrenia.

The authors completed a literature review of all relevant meta-analyses published prior to May 2016.  They included meta-analyses of randomized control trials comparing the effectiveness of combination therapies to monotherapies (one medication only) and/or to placebos. The quality of each meta-analysis was assessed using a tool called AMSTAR. While AMSTAR provides a useful analysis of the quality of the meta-analysis, it does not unfortunately assess the quality of the original studies included in the meta-analysis. To include this important information, the researchers used “AMSTAR – Plus Content” to capture the content quality of the original clinical trials.

The study included 29 meta-analyses, containing data from a total of 381 clinical trials and 19,321 study participants, and providing data 42 different medications. The authors found no compelling evidence to support the use of combination therapies.

This analysis calls into question the results of the 14 meta-analyses reviewed that recommended combination therapies. The authors found that the quality of the meta-analyses was generally very good, but the quality of the original studies ranged significantly. For example, most of the trials included in the meta-analyses had very small sample sizes and/or the results were not replicated in other studies.

This is perhaps due to the fact that clinical trials of this type face challenges such as small sample sizes and publication bias. Studies that show positive results (a significant improvement, or a strong correlation) tend to be published more often than studies that show a negative result (no improvement or correlation). This is known as publication bias and can significantly impact the results of a meta-analysis.

In order to confirm these conclusions, large-scale randomized control trials are needed to truly determine the effectiveness of combination therapy for schizophrenia.


Written By: Lisa Borsellino, B.Sc.

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