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  • Publication # 13-RA007

Study finds few clinically important differences between first- and second-generation medications for treating schizophrenia

Mental Health

Currently, there are 11 first-generation antipsychotics (FGA) and 10 second-generation antipsychotics (SGA) available to treat patients with schizophrenia. Clinicians tend to favor SGAs; 75 percent of patients with schizophrenia were prescribed an SGA in 2003. Despite these preferences, there is controversy over the comparative benefits and disadvantages of FGAs and SGAs. A recent review of studies showed few differences of clinical importance between FGAs and SGAs. A total of 263 publications representing 114 primary studies were identified from the literature for inclusion in the analysis. Of these, 110 were randomized clinical trials. A total of 22 drug comparisons were included. All studies were published between 1974 and 2012.

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Overall, there was low or insufficient strength of evidence from the studies. Wide variation existed in the ways symptoms were measured. In addition, there were only a small number of studies for specific drug comparisons. Nevertheless, the researchers were able to draw some conclusions. First, when it came to treating core illness symptoms, few differences of clinical importance were observed between FGAs and SGAs and those differences depended on the measure used for the symptoms. The FGA haloperidol appeared to be better than the SGA olanzapine for improving positive symptoms, such as hallucinations, delusions, and thought and movement disorders. However, the level of evidence was stronger for SGAs when it came to treating negative symptoms, such as flat affect and the lack of pleasure in everyday life. In this case, olanzapine was better than haloperidol.

Although the strength of evidence was low regarding medication-associated side effects, there was a higher incidence of developing the metabolic syndrome with olanzapine than for haloperidol. A higher incidence of tardive dyskinesia (repetitive and involuntary movements) was found for the FGA chlorpromazine than for the SGA clozapine. No differences in mortality were found for chlorpromazine versus clozapine or haloperidol versus the SGA aripiprazole. The study was supported in part by AHRQ (T32 HS00032).

See "Antipsychotics in adults with schizophrenia: comparative effectiveness of first-generation versus second-generation medications," by Lisa Hartling, Ph.D., Ahmed M. Abou-Setta, M.D., Ph.D., Serdar Dursun, M.D., Ph.D., and others in the October 2, 2012 Annals of Internal Medicine 157(7), pp. 498-511.


Page last reviewed April 2013
Internet Citation: Study finds few clinically important differences between first- and second-generation medications for treating schizophrenia: Mental Health. April 2013. Agency for Healthcare Research and Quality, Rockville, MD.


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