Switching patients with prior antipsychotic exposure to aripiprazole (Abilify) or adding the drug to other combinations did not result in severe psychiatric worsening, a population-based U.K. study found.
Among over 1,600 aripiprazole-treated patients, the rates of psychiatric treatment failure (HR 0.87, 95% CI 0.71-1.06) and hospitalization (HR 0.85, 95% CI 0.69-1.06) were similar to a matched group of patients switching to other antipsychotics, reported Christel Renoux, MD, PhD, of Jewish General Hospital in Montreal, and colleagues.
And no association is seen between aripiprazole use and self-harm or suicide (HR 0.96, 95% CI 0.68-1.36), they wrote in JAMA Psychiatry.
“What has emerged in the literature is several case reports of patients that had worsening of their psychiatric symptoms when they were taking an antipsychotic and then were switched to aripiprazole or added aripiprazole,” Renoux told MedPage Today. This study further examined the signal that emerged across these case reports, she added.
Aripiprazole is an atypical antipsychotic used mostly to treat schizophrenia (initially FDA approved in 2002) and bipolar disorder, and was also approved in 2007 as an add-on treatment for major depressive disorder along with antidepressants.
Although its effectiveness was found to be comparable to other antipsychotics, its pharmacodynamic properties and adverse events profile differ. A 2016 FDA warning, for example, alerted physicians and patients that aripiprazole use may trigger loss of impulse control, leading to “compulsive or uncontrollable urges to gamble, binge eat, shop, and have sex.”
The drug is a partial agonist, which could be one underlying cause of the increase in psychiatric symptoms reported in past case reports, said Ole Thienhaus, MD, MBA, of the University of Arizona of Tucson, who was not a part of the current study. However, Thienhaus emphasized that while this theory could potentially support less severe psychiatric symptom worsening, this would need further examination as the results of the present study do not support it.
“The idea was if you have someone who’s been taking a traditional, non-aripiprazole antipsychotic for a long time, the receptors for dopamine are extremely sensitive,” he told MedPage Today. “When you give that person aripiprazole, that partial agonist function kicks in and strikes those dopamine receptors like thunder and activates all of those psychiatric symptoms again.”
For their study, Renoux’s group linked data from the U.K. Clinical Practice Research Datalink with the Hospital Episodes Statistics repository and the Office for National Statistics mortality database. In order to be included, patients had to be at least age 13 years and have started an oral antipsychotic from 2005 (when aripiprazole was approved in England) to 2015. Individuals with Parkinson’s or Alzheimer’s disease were excluded, as were those with advanced schizophrenia and those who had been initially treated with aripiprazole.
In total, 1,643 patients switching to or adding aripiprazole (57.8% women, mean age 42 years) were included in the study cohort and matched to an equal number of patients starting on another antipsychotic (53% women, mean age 42 years).
Overall, those starting aripiprazole had a slightly lower number of previous psychiatric admissions or self-harm events in the 6 months preceding the study, and a higher number of different previous antipsychotics before study entry. Baseline characteristics were otherwise similar compared with those initiating a different antipsychotic, the authors reported. Most patients in each arm had schizophrenia (42.2%), followed by depression (19.8%), and bipolar disorder (13.4%).
The authors found similar results across most sensitivity analyses they performed. For example, no association was found between initiation of aripiprazole and increased rates of psychiatric treatment failure in patients recently treated with antipsychotic drugs (HR 0.87, 95% CI 0.67-1.15) and patients with schizophrenia (HR 0.82, 95% CI 0.62-1.08), they reported.
Due to the nature of the study, Renoux said it’s still possible that aripiprazole might be associated with psychiatric worsening through measures that are managed outside of the hospital.
Other limitations included the researchers’ inability to track drug adherence, and since prescriptions in the databases used were written by general practitioners, patients who followed up exclusively with a psychiatrist would have been missed. The authors also noted that confounding could be possible, since this study was observational in nature and physicians may preferentially prescribe aripiprazole to patients with less severe psychiatric disease.
The study was supported by infrastructure funding from the Canadian Institutes of Health Research and the Canadian Foundation for Innovation.
One co-author received grant funding from Satellite Healthcare unrelated to this study. No other disclosures were reported.