Mid-Term and Long-Term Efficacy and Effectiveness of Antipsychotic Medications for Schizophrenia: A Data-Driven, Personalized Clinical Approach

Objective: Our aim in this article is 2-fold: first, to examine the mid-term to long-term data on efficacy, from controlled and naturalistic and other studies, in order to determine if they are consistent with the quantitative meta-analyses of mostly short-term, randomized controlled trials Our second (and most important) aim is to use these and other data to provide guidance about the potential relationship of these differences among antipsychotics to the individual patient’s own experience with antipsychotic drugs in the process of shared decision-making with the patients and their significant others.

Data Sources: A search of PubMed, Embase, and PsychINFO was conducted for articles published in English between January 1, 1999, and April 2011, using the search terms double-blind AND randomized AND olanzapine AND (ziprasidone OR risperidone OR quetiapine OR haloperidol OR fluphenazine OR perphenazine OR aripiprazole).

Study Selection: Studies with a duration 3 months or longer, including patients with schizophrenia or schizoaffective disorder, reporting survival analysis for all-cause discontinuation and relapse or dropout due to poor efficacy were selected.

Data Extraction: We extracted the number of patients relapsed due to poor efficacy and hazard rates for relapses.

Data Synthesis: Overall, the efficacy patterns of both controlled effectiveness and observational long-term studies closely parallel the efficacy observed in the short-term, controlled studies. The results of Phase 1 Clinical Antipsychotic Trials of Intervention Effectiveness are very similar to, but not identical with, the controlled short-term efficacy studies, the European First-Episode Schizophrenia Trial, and naturalistic studies. The mid-term and long-term data suggest that olanzapine is more effective than risperidone and that both of these are better than the other first- and second-generation antipsychotics except for clozapine, which is the most efficacious of all. Further large differences emerged regarding the specific mid-term and long-term safety profiles of individual antipsychotics.

Conclusions: Despite intraclass differences and the complexities of antipsychotic choice, the second-generation antipsychotics are important contributions not only to the acute phase but, more importantly, to the maintenance treatment of schizophrenia.

J Clin Psychiatry 2011;72(12):1616-1627

© Copyright 2011 Physicians Postgraduate Press, Inc.

Submitted: February 10, 2011; accepted August 15, 2011

(doi:10.4088/JCP.11r06927).

Corresponding author: Ira D. Glick, MD, 401 Quarry Rd, Ste 3365, Stanford, CA 94305 (iraglick@stanford.edu).