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Original Investigation
January 30, 2019

Association of Aripiprazole With the Risk for Psychiatric Hospitalization, Self-harm, or Suicide

Author Affiliations
  • 1Centre for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, Montreal, Québec, Canada
  • 2Service de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de PharmacoVigilance, Pharmacoépidémiologie et d'Informations sur le Médicament, Centre Hospitalier Universitaire, Faculté de Médecine, Toulouse, France
  • 3Unité clinique de Pharmacologie psychiatrique, Faculté de Médecine, Centre Hospitalier Universitaire, Toulouse, France
  • 4Geri-PARTy Research Group, Department of Psychiatry, Jewish General Hospital, McGill University, Montreal, Québec, Canada
  • 5Aix Marseille Univ, APHM, INSERM, Inst Neurosci Syst, Service de Pharmacologie Clinique et Pharmacovigilance, Marseille, France
  • 6Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Québec, Canada
  • 7Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada
JAMA Psychiatry. 2019;76(4):409-417. doi:10.1001/jamapsychiatry.2018.4149
Key Points

Question  Are patients who switch to or add aripiprazole at an increased risk for psychiatric hospitalization, self-harm, or suicide, compared with switching to or adding another antipsychotic drug?

Findings  In this population-based cohort study of 1643 patients who were starting aripiprazole use, compared with matched patients starting use of another antipsychotic medication, aripiprazole was not associated with an increased risk of hospitalization, self-harm, or suicide.

Meaning  Switching to or adding aripiprazole may be associated with psychiatric worsening in some patients, but the findings suggest that these exacerbations do not lead to serious psychiatric treatment failure; these findings warrant replication in large observational studies.

Abstract

Importance  Some reports have raised concerns regarding a potential psychiatric worsening associated with first-time use of aripiprazole in patients already treated with other antipsychotic medications. Whether aripiprazole use, particularly in the long term, increases the risk for serious psychiatric events is unclear.

Objective  To assess whether switching to or adding aripiprazole is associated with serious psychiatric treatment failure compared with switching to or adding another antipsychotic drug in patients previously exposed to antipsychotic medications.

Design, Setting, and Participants  This population-based cohort study was conducted from January 1, 2005, to March 31, 2015. Data were obtained from the United Kingdom Clinical Practice Research Datalink, one of the world’s largest computerized databases linked to the Hospital Episodes Statistics repository and the Office for National Statistics (ONS) mortality database. Within a base cohort of new users of antipsychotic drugs, patients switching or adding aripiprazole (n = 1643) were propensity matched 1:1 to patients switching to or adding another antipsychotic medication (n = 1643). All patients were followed up until psychiatric treatment failure, for 365 days (1 year) after cohort entry, until death from any cause other than suicide, until end of registration or linkage with the databases, or end of the study period (March 31, 2016).

Main Outcomes and Measures  Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of serious events of psychiatric treatment failure (psychiatric hospitalizations, self-harm, or suicide) associated with switching to or adding aripiprazole compared with other antipsychotic drugs. In addition to propensity score matching, all models were adjusted for age, number of psychiatric hospitalizations or self-harm events in the 6 months before cohort entry, number of different antipsychotic drugs before cohort entry, and quintiles of the Index of Multiple Deprivation.

Results  The study cohort included 1643 patients (949 [57.8%] were women with a mean [SD] age of 42.1 [16.8] years) starting aripiprazole use; they were matched 1:1 to 1643 patients (871 [53.0%] were women with a mean [SD] age of 42.4 [17.1] years) starting use of another antipsychotic drug. During 2692 person-years of follow-up, 391 incident serious psychiatric treatment failures occurred, with a crude incidence rate of 14.52 (95% CI, 13.16-16.04) per 100 person-years. First-time use of aripiprazole was not associated 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) compared with starting use of another antipsychotic drug. Results were consistent across several sensitivity analyses.

Conclusions and Relevance  Initiating aripiprazole use, compared with another antipsychotic medication, after a previous antipsychotic exposure did not appear to be associated with psychiatric hospitalization, self-harm, or suicide; these findings warrant replication in large observational studies.

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