Antipsychotics with the lowest risk for schizophrenia relapse included clozapine and any of the long-acting injectable antipsychotics, according to a study published in JAMA Psychiatry. Similar to clozapine, injectable paliperidone, zuclopenthixol, perphenazine, and olanzapine were associated with about half the risk for psychiatric rehospitalization and reduced risks for other treatment failure, the authors found.

“Our results showed that the risk of rehospitalization was 22% lower during treatment with long-acting injectable antipsychotic medications compared with treatment with equivalent oral formulations in the total cohort and 32% lower in the incident cohort of newly diagnosed patients,” reported Jari Tiihonen, MD, PhD, from the Karolinska Institutet in Stockholm, Sweden, and colleagues.

“The most consistent findings were observed for clozapine, being the first in rank order in most of the analyses,” they added.

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Starting in July 2006, the researchers prospectively tracked all Swedish adults between ages 16 and 64 years who had a diagnosis of schizophrenia at that time through December 2013. Average age was 45 years. The 29,823 patients included 4603 newly diagnosed in that period, and all patients served as their own controls to eliminate selection bias.

Outcomes included rehospitalization risk and treatment failure, defined as psychiatric rehospitalization, suicide attempt, discontinuing or switching to a different drug, or death. The researchers adjusted their analysis to account for disease duration, other nonpsychotic medications, and the order of periods when they were and were not taking antipsychotics.

During more than 7 years of follow-up, 43.7% of patients were rehospitalized. Compared with those not taking any antipsychotics, those receiving monotherapy with any of the following agents were approximately half as likely have psychiatric rehospitalization: clozapine, monthly injections of long-acting paliperidone, and injections of long-acting zuclopenthixol, perphenazine, or olanzapine.

Treatments associated with the highest risk for rehospitalization included oral flupentixol, quetiapine, and oral perphenazine. In line with both those findings, rehospitalization risk was 20% to 30% lower for long-acting injectable antipsychotics compared with their equivalent oral formulations.

Overall, 71.7% of the patients experienced treatment failure. Compared with oral olanzapine, the most commonly prescribed medication, the lowest rates of treatment failure occurred among those taking clozapine or any of the long-acting injectable antipsychotics.

“It is remarkable that the risk of psychiatric rehospitalization, being a marker for relapse, was about 40% to 70% higher during monotherapy with quetiapine than during monotherapy with clozapine, oral olanzapine or the most frequently used long-acting injectable antipsychotic medications,” the authors wrote, noting that many countries use quetiapine most frequently. “Our results are in line with those of previous studies suggesting that quetiapine should not be used routinely as monotherapy for patients with schizophrenia without specific reasons,” they concluded.

The researchers hypothesized that patients taking oral medications could have elected to take lower doses than prescribed, which is not possible with the injectable medications, as one potential reason for the superiority of injectables in preventing relapse.

“The better outcomes associated with clozapine and long-acting injectable antipsychotic medications may be partly explained by the more regular contact with medical staff necessitated by blood samples and injections,” the authors also wrote. “However, from the view of patients and their families, it is irrelevant which specific factor in the chosen treatment plan contributes most to the outcome.”

Although more frequent healthcare visits cost more in the short-term, rehospitalization prevention nets greater savings, they added. The study was funded by Janssen-Cilag.

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Tiihonen J, Mittendorfer-Rutz E, Majak M, et al. Real-world effectiveness of antipsychotic treatments in a nationwide cohort of 29 823 patients with schizophrenia [published online June 7, 2017]. JAMA Psychiatry. doi: 10.1001/jamapsychiatry.2017.1322