Paliperidone 3-Month LAI Bests Other Antipsychotics for Preventing Relapse, Treatment Failure in Schizophrenia

Aleksi Hamina, PhD
Credit: LinkedIn

Less than 2 weeks after the US Food and Drug Administration’s approval of xanomeline and trospium chloride capsules (Cobenfy) ushered in a new era of management for schizophrenia spectrum disorder, data from a study of more than 130,000 individuals is shedding light on the comparative effectiveness of the previous generation of antipsychotic therapies among this patient population.^1,2

Led by investigators from Finland, Norway, and Sweden, the analysis, which leveraged data from Swedish health care registers of inpatient and outpatient care for all people aged 16 to 65, provides evidence of considerable variability in risk of relapse and treatment failure across different antipsychotic treatments. According to investigators, these findings directly contradict previous notions suggesting all antipsychotics provided equal effectiveness in relapse prevention for this patient population.²

“To our knowledge, this is the largest study to date to investigate antipsychotic effectiveness in patients with schizophrenia spectrum disorders, which enabled us to detect many statistically significant findings despite a large number of specific medications and corrections for multiple comparisons,” wrote investigators.²

With the association between psychotic relapse and negative outcomes well-documented, prevention of relapse remains a cornerstone of optimal management. With antipsychotic medications offering the potential for improved relapse prevention, identifying optimal first-line antipsychotics stands to have a significant impact on overall health and quality of life in patients with schizophrenia.²

Citing a lack of definitive evidence on differences in the effectiveness of antipsychotic treatments, a team led by Aleksi Hamina, PhD, of Niuvanniemi Hospital in Finland, designed the current study as a comparative effectiveness analysis of data recorded within Swedish health care registers of inpatient and specialized outpatient care, sickness absence, and disability pensions among all people aged 16 to 65 years diagnosed with schizophrenia spectrum disorder from January 1, 2006 through December 31, 2021. Of note, as part of the design of their study, investigators created an incident and prevalent cohort.²

Are you interested in more updates on schizophrenia management? Check out this 5-part series examining how the approval of Cobenfy impacts the treatment landscape!

The primary outcome of interest were the risks for psychosis relapse hospitalization or treatment failure after adjustment for temporal order of treatments, time since cohort entry, and concomitant drugs. Investigators pointed out treatment failure was defined as a psychiatric hospitalization, death, or change in an antipsychotic medication and, for the purpose of analysis, all antipsychotics were compared against oral olanzapine.²

A total of 131,476 individuals were identified for inclusion in the study. This cohort had a mean age of 45.7 (SD, 16.2) years and 53.3% were men. Among this group, the median follow-up was 12 (IQR, 5.2 to 16.0) years and, during the follow-up, 48.5% of patients experiencing red relapse and 71.5% experienced treatment failure at least once.²

Among 23 different antipsychotics included in the analysis, paliperidone 3-month long-acting injectable (LAI) was associated with the lowest adjusted hazard ratio (aHR) in the prevention of relapses (aHR, 0.66; 95% Confidence Interval [CI], 0.51-0.86) relative to oral olanzapine. Further analysis suggested a reduced risk was also observed with aripiprazole LAI (aHR, 0.77; 95% CI, 0.70 to 0.84), olanzapine LAI (aHR, 0.79; 95% CI, 0.73 to 0.86), and clozapine (aHR, 0.82; 95% CI, 0.79 to 0.86). Investigators highlighted the greatest risk of relapse relative to oral olanzapine was observed with quetiapine (aHR 1.44; 95% CI, 1.38 to 1.51).²

When assessing the risk of treatment failure, the greatest reduction in risk was observed with paliperidone 3-month LAI (aHR, 0.36; 95% CI, 0.31 to 0.42). A reduction in risk was also observed with aripiprazole LAI (aHR, 0.60; 95% CI, 0.57-0.63), olanzapine LAI (aHR, 0.67; 95% CI, 0.63 to 0.72), and paliperidone 1-month LAI (aHR, 0.71; 95% CI, 0.68 to 0.74). In contrast, the greatest risk was observed with paliperidone oral (aHR, 1.70; 95% CI, 1.63 to 1.78).²

Investigators spotlighted multiple limitations within their study to consider. These included, but were not limited to, the possibility of selection and consequent residual confounding in results, the possibility prior stabilization on shorter-acting LAIs may have inflated results for paliperidone 3-month LAI, and potential confounding by indication.²

“The findings, combined with previous results from [randomized clinical trials], suggest that it may be beneficial to initiate treatment with the most effective antipsychotics that are available as both oral and LAI formulations,” investigators added.²

References:

1. Derman C. FDA approves Xanomeline and Trospium Chloride (Cobenfy) for schizophrenia. HCP Live. September 26, 2024. Accessed October 10, 2024. https://www.hcplive.com/view/fda-approves-xanomeline-and-trospium-chloride-cobenfy-for-schizophrenia.
2. Hamina A, Taipale H, Lieslehto J, et al. Comparative Effectiveness of Antipsychotics in Patients With Schizophrenia Spectrum Disorder. JAMA Netw Open. 2024;7(10):e2438358. doi:10.1001/jamanetworkopen.2024.38358