Paliperidone Palmitate Demonstrates Long-Term Efficacy, Safety for Schizophrenia

Over 95% of patients with schizophrenia receiving long-acting injectable (LAI) paliperidone palmitate, administered twice a year, remained relapse-free for up to 3 years, according to study findings published in JAMA Network Open.

Relative to oral antipsychotics, LAI formulations of antipsychotics have demonstrated superior efficacy and have the potential to improve adherence to treatment and symptom control among patients with schizophrenia. Paliperidone palmitate is the first LAI with a 6-month dosing interval for patients who have been adequately treated with paliperidone palmitate once monthly for 4 months or longer or paliperidone palmitate every 3 months. To evaluate the long-term treatment outcomes of paliperidone palmitate every 6 months among adults with schizophrenia, investigators conducted a secondary analysis of a 1-year, double-blind randomized clinical trial (NCT03345342) and its 2-year, single-arm, open-label extension study (NCT04072575).

For the present analysis, the investigators included adults with schizophrenia who had no relapse during the 1-year randomized trial while receiving paliperidone palmitate every 6 months and then chose to continue flexible dosing paliperidone palmitate for 2 years between 2017 and 2022. The primary outcomes of interest were the changes in Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression–Severity (CGI-S) Scale, and Personal Social Performance (PSP) Scale scores.

A total of 121 participants were included for this analysis. At screening for the original double-blind trial, the participants had a mean (SD) age of 38.6 (11.24) years, a BMI of 27.5 (SD, 9.21 kg/m²), a duration of schizophrenia of 11.0 (9.45) years, 68.6% were men, and 16.5% were taking an LAI antipsychotics. At baseline, the participants had a mean (SD) PANSS score of 53.4 (9.72), CGI-S score of 3.0 (0.77), and PSP score of 68.7 (12.10).

During the open-label extension, patients received an average paliperidone palmitate dose of 1367.7 mg.

A total of 4.1% of patients had a relapse event during the 3-year follow-up. The relapses involved psychiatric hospitalization (n=2), suicidal or homicidal ideation (n=2), and deliberate self-injury (n=1).

From baseline to the end of the study, the investigators observed that the mean (SD) change in PANSS score was -2.6 (9.96), in CGI-S score was -0.2 (0.57), and in PSP score was 3.1 (9.14), indicating stable outcomes. In subgroup analyses, clinical outcomes were overall consistent with these findings, with the exception that women had more improved CGI-S scores relative to men.

Treatment-emergent adverse events were reported by 80.2% (n=97) of the participants. The investigators found that the adverse events were possibly related to treatment in 53.7% of reported adverse events, 5.8% were serious, and 5.0% led to drug discontinuation. The most common events included blood prolactin increase or hyperprolactinemia (19.0%), headache (18.2%), weight gain (12.4%), nasopharyngitis (10.7%), and injection site pain (10.7%).

“In a 2-year [open-label extension] study of a 1-year randomized clinical trial, a high proportion (95.9%) of patients receiving [ paliperidone palmitate] once every 6 months remained relapse free for up to 3 years with no new safety concerns emerging and with high treatment persistence,” the investigators concluded. “The findings suggest that [ paliperidone palmitate] every 6 months, the first antipsychotic to date that can be administered effectively only twice per year, adds to the range of long-term treatment options for patients with schizophrenia.”

These study results may be limited, as there was a lack of a comparator group and these findings may not be generalizable for patients who experience relapse within the first year of LAI paliperidone palmitate treatment, as these patients were not included in the open-label extension.

Disclosure: This research was supported by Janssen Scientific Affairs, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Psychiatry Advisor