Some Popular Antipsychotics May Not be Effective in Patients over 40

Research Updates in PsychiatryAtypical antipsychotics are widely prescribed for a number of psychiatric diagnoses, but their real-world effectiveness has rarely been evaluated in anything other than short-term trials. A recently published study finds that four commonly used antipsychotics (aripiprazole [Abilify], olanzapine [Zyprexa], quetiapine [Seroquel], and risperidone [Risperdal]), when used in patients over age 40 with schizophrenia or psychosis associated with other conditions, may not be effective—and cause frequent side effects.

Investigators studied 332 psychiatric outpatients, mean age 66.6 years, for up to two years. Most (61%) did not have a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder. In fact, depression, PTSD, and dementia were highly represented. All were considered candidates for atypical antipsychotics by their psychiatrists. Each patient was given the opportunity to identify one or two (or none) of the drugs as “unacceptable”; patients were randomized to one of the two, three, or four remaining drugs on their list, at doses determined by their prescribers.

Surprisingly, none of the four drugs provided any symptomatic improvement as observed on the total Brief Psychiatric Rating Scale (BPRS) or BPRS psychosis subscale, and no drug emerged as more effective than any other. (There was no placebo control for ethical reasons.) The one-year incidence of metabolic syndrome was 36.5%, likewise with no significant difference among the medications. Serious adverse events were observed in 23.7% of the patients and nonserious events in 50.8% across the two-year study period. Serious events included deaths, hospitalizations, and emergency room visits.

The median length to discontinuation of medication was short, only 26 weeks. The proportion of patients who stayed on their drug of choice for the entire two years ranged from only 18.5% (aripiprazole) to 21.4% (quetiapine). Reasons for discontinuation included side effects (51.6%), lack of effectiveness (26.9%) or other reasons. No individual diagnosis had a better outcome, and certain perceived “advantages” of individual drugs were not borne out (for example, metabolic syndrome was not less common with aripiprazole). The quetiapine arm was discontinued by the study’s safety monitoring board because of the significantly higher incidence (38.5% vs 19.0% for all other drugs) of serious adverse effects with this drug (Jin H et al, J Clin Psychiatry 2012; epub online ahead of print).

TCPR’s Take: This study should not be dismissed as yet another appeal to use caution when prescribing antipsychotics in older patients. It actually sends an even more powerful message: these four atypical antipsychotics had no significant effect on psychopathology as measured by total BPRS score or the BPRS psychosis subscale. The most prominent “positive” finding, in fact, was the appearance of side effects in more than half the patients. Moreover, the study population was adults over 40 (not exactly the “elderly”). The authors conclude that the results are “worrisome” and “sobering” and we concur. If atypicals are to be used at all in this population, they’re probably best used in the short-term only, and discontinued if adverse effects arise.

Some Popular Antipsychotics May Not be Effective in Patients over 40

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This article was published in print 1/2013 in Volume:Issue 11:1.


APA Reference
Spielmans,, G. (2014). Some Popular Antipsychotics May Not be Effective in Patients over 40. Psych Central. Retrieved on December 4, 2020, from


Scientifically Reviewed
Last updated: 23 Jun 2014
Last reviewed: By John M. Grohol, Psy.D. on 23 Jun 2014
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