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Long-acting injectable antipsychotics best for relapse in schizophrenia

Long-acting injectable antipsychotic medications and clozapine were associated with highest rates of prevention of relapse in schizophrenia, according to recent findings.

“The comparative effectiveness of antipsychotic treatments for patients with schizophrenia has remained controversial despite extensive research,” Jari Tiihonen, MD, PhD, of Karolinska Institutet, Stockholm, and colleagues wrote. “Results from randomized clinical trials suggest that clozapine, olanzapine, and amisulpiride are superior to other antipsychotic medications in terms of efficacy. However, the most efficacious drugs such as clozapine and olanzapine frequently induce adverse effects, such as weight gain and dyslipidemia, which may result in severe deterioration of health after long-term treatment.”

To assess real-world effectiveness of antipsychotic treatments for schizophrenia, researchers analyzed linked data from nationwide databases to determine risk for rehospitalization and treatment failure among all individuals in Sweden with schizophrenia aged 16 to 64 years. The total prevalent cohort included 29,823 individuals and 4,603 were in the incident cohort of newly diagnosed patients. Participants had a mean age of 44.9 years.

During follow-up, 43.7% of participants were rehospitalized and 71.7% experienced treatment failure.

Risk for psychiatric rehospitalization was lowest during monotherapy with once-monthly long-acting injectable paliperidone (HR = 0.51; 955 CI, 0.41-0.64), long-acting injectable zuclopenthixol (HR = 0.53; 95% CI, 0.48-0.57), clozapine (HR = 0.53; 95% CI, 0.48-0.58), long-acting injectable perphenazine (HR = 0.58; 95% CI, 0.52-0.65), and long-acting injectable olanzapine (HR = 0.58; 95% CI, 0.44-0.77), compared with no use of antipsychotics.

Highest risk for rehospitalization was associated with oral flupentixol (HR = 0.92; 95% CI, 0.74-1.14), quetiapine (HR = 0.91; 95% CI, 0.83-1), and oral perphenazine (HR = 0.86; 95% CI, 0.77-0.97).

Compared with equivalent oral formulations, long-acting injectable antipsychotic medications were associated with significantly lower risk for rehospitalization in the total cohort (HR = 0.78; 95% CI, 0.72-0.84) and incident cohort (HR = 0.68; 95% CI, 0.53-0.86).

Clozapine (HR = 0.58; 95% CI, 0.53-0.63) and all long-acting injectable antipsychotic medications (HRs = 0.65-0.8) were associated with lowest rates of treatment failure, compared with oral olanzapine, the most commonly used medication.

These findings were consistent with several sensitivity analyses, according to researchers.

“Our results suggest that there are substantial differences between specific antipsychotic agents and between routes of administration concerning the risk of rehospitalization and treatment failure among patients with schizophrenia,” the researchers concluded. – by Amanda Oldt

Disclosure: Tiihonen reports serving as a consultant to the Finnish Medicines Agency Fimea, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-La Roche, Janssen-Cilag, Lundbeck, and Organon; receiving fees for giving expert testimonies to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Otsuka, and Pfizer; receiving lecture fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Novartis, Otsuka, and Pfizer; receiving grants from the Stanley Foundation and the Sigrid Jusélius Foundation; serving as a member of the advisory boards for AstraZeneca, Eli Lilly, Janssen-Cilag, and Otsuka; and participating in research projects funded by Janssen-Cilag and Eli Lilly with grants paid to the Karolinska Institutet. Please see the study for a full list of relevant financial disclosures.