To compare longer-term safety and effectiveness of the four most commonly used atypical antipsychotics (AAPs: aripiprazole, olanzapine, quetiapine, and risperidone) in 332 patients, aged >40 years, having psychosis associated with schizophrenia, mood disorders, PTSD, or dementia, diagnosed using DSM-IV-TR criteria.
We used Equipoise-Stratified Randomization (a hybrid of Complete Randomization and Clinician’s Choice Methods) that allowed patients or their treating psychiatrists to exclude one or two of the study AAPs, because of past experience or anticipated risk. Patients were followed for up to two years, with assessments at baseline, 6 weeks, 12 weeks, and every 12 weeks thereafter. Medications were administered employing open-label design and flexible dosages, but with blind raters.
(1) Primary metabolic markers (body mass index or BMI, blood pressure, fasting blood glucose, LDL cholesterol, HDL cholesterol, and triglycerides), (2) % patients who stay on the randomly assigned AAP for at least 6 months, (3) Psychopathology, (4) % patients who develop Metabolic Syndrome, and (5) % patients who develop serious and non-serious adverse events.
Because of high incidence of serious adverse events, quetiapine was discontinued midway through the trial. There were significant differences among patients willing to be randomized to different AAPs, suggesting that treating clinicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with metabolic problems. Yet, the AAP groups did not differ in longitudinal changes in metabolic parameters or on most other outcome measures. Overall results suggested a high discontinuation rate (median duration 26 weeks prior to discontinuation), lack of significant improvement in psychopathology, and high cumulative incidence of metabolic syndrome (36.5% in one year) and of serious (23.7%) and non-serious (50.8%) adverse events for all AAPs in the study.
Employing a study design that closely mimicked clinical practice, we found a lack of effectiveness and a high incidence of side effects with four commonly prescribed AAPs across diagnostic groups in patients over age 40, with relatively few differences among the drugs. Caution in the use of these drugs is warranted in middle-aged and older patients.