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Atypical Antipsychotics for Schizophrenia: Combination Therapy and High Doses [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2011 Dec. (CADTH Optimal Use Report, No. 1.1.)

Cover of Atypical Antipsychotics for Schizophrenia: Combination Therapy and High Doses

Atypical Antipsychotics for Schizophrenia: Combination Therapy and High Doses [Internet].

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Summary with Action Plan

In Canada, the most frequently prescribed atypical antipsychotics combinations include Risperdal, Seroquel, and Zyprexa. Yet, not a single randomized controlled trial (RCT) was found to support the efficacy or safety of these combinations despite a comprehensive systematic review by the Canadian Agency for Drugs and Technologies in Health (CADTH).

The available evidence identified few clinical advantages and uncertain harms when using combination or high-dose strategies for patients with schizophrenia who have an inadequate response to an antipsychotic.

No advantages found

Combination strategy: The evidence examining the use of two antipsychotics simultaneously compared with monotherapy is limited to 13 RCTs of short duration. Meta-analyses of these trials by CADTH revealed no clinically important differences in response rate, schizophrenia symptoms, extrapyramidal side effects, akathisia, metabolic side effects, or hospitalization rates between monotherapy and combination therapy. With insufficient evidence to accurately assess harms, the risks associated with atypical antipsychotic combination therapy are largely unknown.

High-dose strategy: Ten RCTs of short duration examined higher-than-recommended atypical antipsychotic dosing compared with standard dosing. No consistent evidence was found to suggest that going beyond the maximum recommended dose led to improved outcomes, and the potential harms of this approach are uncertain.

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Copyright © 2011 Canadian Agency for Drugs and Technologies in Health.
Bookshelf ID: NBK169706
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