New Aripiprazole Patients Not at Worse Risk for Self-Harm, Hospitalization

Francois Montrastruc, MD, PhD

Antipsychotic therapy aripiprazole is not linked to any greater risk for psychiatric hospitalization, self-harm, or suicide, when compared to a similar therapy, according to a new cohort analysis.

A team of investigators set in Québec, CA, and France have shared new findings showing that there were no significant differences in severe psychiatric adverse effects in patients to have switched to or added ariprazole to their antipsychotic drug regimen, when compared to patients to have switched to or added a similar oral therapy.

The findings come conversely to a recorded history of abrupt psychotic worsening in patients who switched to aripiprazole. The atypical oral antipsychotic is used primarily to treat schizophrenia and bipolar disorder (BPD), as well as symptoms associated with major depressive disorder and autism.

In an interview with MD Magazine®, study author François Montrastruc, MD, PhD, clinical psychopharmacologist and specialist in pharmacoepidemiology, Toulouse University noted the therapy’s side effect profile differs from other antipsychotics—explaining its clinical preference for BPD and schizophrenia. Metabolic side effects such as weight gain or risk of diabetes are significantly reduced with aripiprazole compared to other drugs.

“However, there were some concern that aripiprazole may rarely provoke a worsening of the psychiatric disease, especially in patients previously treated with other antipsychotics,” Montrastruc said.

To test this belief, Montrastruc and colleagues obtained data from the United Kingdom Clinical Practice Research Datalink (CPRD), a conglomerate database of 15 million-plus patients from approximately 700 UK general practices. They assembled a cohort of patients 13 years of age and older to have initiated oral antipsychotic drug use between January 2005 and March 2015.

Patients were required to have at least 1 year of medical history in the CPRD without any antipsychotic prescriptions before their first oral prescription. Patients with Parkinson or Alzheimer disease were excluded, in order to limit the antipsychotic therapy assessment to patients with psychiatric disease.

Investigators used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of psychiatric hospitalizations, self-harm, and suicide associated with switching to or adding aripiprazole, in comparison to other antipsychotics.

Their cohort included 1643 patients on aripirprazole. A majority (57.8%) were women, with a mean age of 42.1 years at aripiprazole initiation. Investigators matched them 1:1 to patients who started use on another antipsychotic drug at a mean age of 42.4 years. In 2692 person-years of observation, the team found 391 incident serious psychiatric treatment failures to have occurred—giving a crude incidence rate of 14.52 (95% CI: 13.16-16.04) per 100 person-years.

There was no found association with an increased rate of psychiatric treatment failure (HR, 0.87; 95% CI: 0.71-1.06), psychiatric hospitalizations (HR, 0.85; 95% CI: 0.69-1.06), or self-harm or suicide (HR, 0.96; 95% CI: 0.68-1.36) in first-time aripiprazole patients compared to patients initiating another antipsychotic.

In assessing patients with schizophrenia, initiating aripiprazole was not associated any increased risk of psychiatric treatment failure. Investigators noted that similar, more recent assessments have added to the growing evidence that switched-on or added-on aripiprazole is not associated with psychotic harm in psychiatric patients. Rather, such adverse effects may be more driven by a patient’s exposure to excessive antipsychotic doses in the past.

“Our findings are reassuring for the prescription of aripiprazole, regarding serious psychiatric outcomes, such as psychiatric hospitalization or self-harm/suicide,” Montrastruc said. “However, our findings do not exclude a differential risk of non-serious psychiatric exacerbations not leading to psychiatric hospitalization.”

Despite the findings, Montrasuc advised clinicians continue to monitor patients for psychiatric exacerbations when switching to or adding aripiprazole.

The study, "Association of Aripiprazole With the Risk for Psychiatric Hospitalization, Self-harm, or Suicide," was published online in JAMA Psychiatry.