Four atypical antipsychotics most commonly prescribed off-label for use in patients aged at least 40 years were found to lack effectiveness and safety, according to the results of a 5-year comparison study.
“Our study suggests that off-label use of these drugs in older people should be short term and undertaken with caution,” study researcher Dilip V. Jeste, MD, of the University of California, San Diego, and president of the American Psychiatric Association (APA), said in a press release.
The APA was not involved in the study.
Jeste and colleagues studied the effects of off-label uses of aripiprazole (Abilify, Otsuka), olanzapine (Zyprexa, Lilly), quetiapine (Seroquel, AstraZeneca) and risperidone (Risperdal, Janssen) in 332 patients aged at least 40 years who were diagnosed with psychosis associated with schizophrenia, mood disorders, posttraumatic stress disorder or dementia.
The researchers used equipoise-stratified randomization, which allowed patients or their treating psychiatrists to exclude one or two of the antipsychotics based on anticipated risks or past experience with the drugs. Patients were assessed at baseline, 6 weeks, 12 weeks and again every 12 weeks for 2 years.
“Our goal was to ensure clinical relevance,” Jeste said. “We attempted to make the study as ‘user-friendly’ as possible, to allow the drugs the best chance of success, while seeking to minimize the amount of bias.”
Within 1 year of treatment, 36.5% of patients developed metabolic syndrome. Within 2 years, 50.8% of patients developed non-serious, and 23.7% serious, adverse events from all antipsychotics used in the study. Serious adverse events included deaths, hospitalizations and emergency room visits for life-threatening conditions.
The researchers had intended that patients remain on the randomly assigned antipsychotics for 2 years, but the median length of treatment was 26 weeks, after which time the atypical antipsychotic was discontinued or switched. Among patients whose reasons for discontinuation were known, 51.6% did so due to adverse effects, 26.9 % for lack of effectiveness and 21.5% for other reasons. The researchers also found no significant change in psychopathology with any of the four atypical antipsychotic drugs.
According to the researchers, there were significant differences among patients willing to be randomly assigned to a different medication (P<.01), indicating that psychiatrists tended to exclude olanzapine and opt for aripiprazole for patients who had developed metabolic problems. However, the four drugs did not tend to differ in most outcome measures.
“When these medications are used off-label, they should be given in low dosages and for short durations, and their side effects monitored closely,” Jeste said. “Clearly, there is also a critical need to develop and test new interventions that are safe and effective in older people with psychotic disorders.”
Disclosure: Study researcher Sunder Mudaliar, MD, is a consultant and on the speakers’ bureau for AstraZeneca and Bristol-Myers Squibb, which manufactured the drugs used in this study.