Aripiprazole Self-harm, Suicide Risk: Is It Real?

Contrary to previous findings, use of the antipsychotic aripiprazole (multiple brands) does not appear to be associated with higher risk for psychiatric hospitalization, self-harm, or suicide, new research suggests.

Investigators compared 1643 patients to 1643 matched control persons who were switching to or adding another antipsychotic medication.

Patients were followed until either psychiatric treatment failure occurred (defined as hospitalization for a psychiatric event, self-harm, or suicide), or 1 year had passed since entrance into the study, or death from some cause other than suicide occurred.

Initiation of aripiprazole did not appear to be associated with psychiatric hospitalization, self-harm, or suicide, compared to initiation of other antipsychotic medications.

“We find that switching to or adding aripiprazole in patients previously treated with antipsychotics was not associated with psychiatric hospitalization, self-harm, or suicide, compared to switching to or adding another antipsychotic,” lead author Christel Renoux, MD, PhD, assistant professor, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada, told Medscape Medical News.

“We did not find evidence of serious psychiatric worsening when switching or adding aripiprazole, compared with other antipsychotics, but we cannot rule out a potential risk of nonserious worsening; therefore, patients should still be monitored for psychiatric exacerbations when switching or adding aripiprazole around the time of treatment start,” she said.

The study was published online January 30 in JAMA Psychiatry.

Worsening Symptoms?

“We undertook this study because aripiprazole is a frequently used antipsychotic with an interesting profile, with reduced metabolic adverse effects, for instance, compared with some other antipsychotics,” Renoux recounted.

“However, there are some concerns from case reports of a possible psychiatric worsening in some patients when they start aripiprazole after being treated with other antipsychotics,” she said.

The researchers therefore wanted to study the risk for worsening psychiatric symptoms in a larger cohort with longer follow-up.

To investigate the question, the researchers used the United Kingdom Clinical Practice Research Datalink (CPRD), one of the world’s largest databases, consisting of 15 million deidentified primary care patients in 700 general practices in the United Kingdom.

They assembled a cohort of all patients in the CPRD who were aged 13 years or older and who initiated use of an oral antipsychotic drug between January 1, 2005, and March 31, 2015.

Patients were required to have not received a prescription for an antipsychotic for at least 1 year before receiving their first oral antipsychotic.

Patients who were initially treated with aripiprazole and those with advanced schizophrenia, Parkinson’s disease, or Alzheimer’s disease before cohort entry were excluded.

The researchers further identified a study cohort consisting of all patients who received a prescription for aripiprazole or another oral antipsychotic drug either as a switch from or an add-on to a previous antipsychotic medication from the beginning of the study period.

Each patient who started treatment with aripiprazole was then matched in a 1:1 ratio to another patient who started a different antipsychotic drug. Patients were matched on the basis of calendar year of cohort entry (within 5 years), time since the first antipsychotic prescription (within 6 months), psychiatric disease history, and time-conditional propensity score.

Patients were followed until any one of the following events or constraints occurred: psychiatric treatment failure; the passage of 1 year since being included in the cohort; death from any cause other than suicide; end of registration with the CPRD-enrolled medical practice; or end of the study period (March 31, 2016).

More Research Needed

The primary outcome was first psychiatric treatment failure, which was a composite of psychiatric hospitalization, self-harm, or suicide.

The study cohort included 1643 patients (57.8% female, mean [SD] age 42.1 [16.8] years) who were initiating use of aripiprazole. Patients were matched in a 1:1 ratio to 1643 patients (53.0% female, mean age, 42.4 [17.1] years) who were starting use of another antipsychotic drug.

Both groups of patients had similar baseline profiles. However, those starting aripiprazole had slightly fewer previous psychiatric admissions (18.3% vs 22.5%) and episodes of self-harm (3.0% vs 4.6%) in the 6 months before cohort entry, as compared to those starting another drug.

They also had received a higher number of different antipsychotic drugs prior to cohort entry (mean, 0.9 [0.5] vs 0.7 [0.6]).

There were 391 incident psychiatric treatment failures during the 2692 person-years of follow-up, yielding a crude incidence rate of 14.52 (95% confidence interval [CI], 13.16 – 16.04) per 100 person-years.

Aripiprazole initiation was not associated with an increased rate of psychiatric treatment failure, compared with initiation of another antipsychotic medication (hazard ratio [HR], 0.87; 95% CI, 0.71 – 1.06).

Moreover, when assessed separately, no association was found between aripiprazole initiation and psychiatric hospitalization or self-harm/suicide (HR, 0.85; 95% CI, 0.69 – 1.06; and HR, 0.96; 95% CI, 0.68 – 1.36, respectively).

When analyses were conducted with respect to particular subgroups, such as patients recently treated with antipsychotic drugs and patients with schizophrenia, the researchers found that initiation of aripiprazole was not associated with an increased rate of failure in any subgroup.

Secondary and sensitivity analyses yielded similar findings.

The authors comment that they “could not exclude a potential risk of psychiatric treatment failure in patients with more severe psychiatric disease” who are switched to aripiprazole.

“Thus, further investigation is needed in patients who were highly exposed to antipsychotic drugs before switching to aripiprazole,” they write.

They note several additional limitations of their findings.

One is that prescriptions in the CPRD database were issued by general practitioners, and there were no data on medications prescribed by specialists, so information regarding patients with unstable psychiatric disease who received further consultation with a psychiatrist may not have been captured.

Moreover, the findings “do not exclude a differential risk for nonserious psychiatric exacerbations that do not lead to psychiatric hospitalization,” they add.

“Well-Conducted” Research

Commenting on the study for Medscape Medical News, Roger McIntyre, MD, professor of psychiatry and psychopharmacology, and head, Mood Disorders Psychopharmacology Unit, University Health Network, University of Toronto, Canada, who was not involved with the research, described it as a “well-conducted study.”

“I don’t actually believe that antipsychotic medications worsen psychiatric illness,” he said. “The fact that they [the investigators] didn’t find this aligns with my belief system [and they] provided evidence supporting what I already don’t believe,” he added.

The authors note that their results “warrant replication in larger population-based studies.”

The study was supported by infrastructure funding from the Canadian Institutes of Health Research and the Canadian Foundation for Innovation. Renoux reports no relevant financial relationships. The other authors’ disclosures are listed on the original article. McIntyre reports receiving research funds or grants from the Stanley Medical Research Institute and CIHR/GACD/Chinese National Natural Research Foundation and receiving consultation/speaker fees from Lundbeck, Janssen, Shire, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, and Minverva.

JAMA Psychiatry. Published online January 31, 2019. Abstract

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