Adults with schizophrenia get long-term benefits with paliperidone palmitate

More than 90 percent of adult patients with schizophrenia who continued to receive the long-acting injectable (LAI) antipsychotic paliperidone palmitate for another 2 years after completing a 1-year treatment course remained relapse-free, with no new safety signals emerging, according to an open-label extension (OLE) study.

The relapse-free rate with paliperidone palmitate treatment every 6 months for up to 3 years was 95.9 percent. Reasons for relapse in five patients (4.1 percent) included psychiatric hospitalization (n=2), suicidal or homicidal ideation (n=2), and deliberate self-injury (n=1). [JAMA Netw Open 2024;7:e2421495]

Apart from the low relapse rate, clinical and functional stability was observed among the patients. This was evidenced by minimal changes in total scores on the Positive and Negative Syndrome Scale (PANSS; −2.6 points), Clinical Global Impression–Severity (CGI-S) scale (−0.2 points), and Personal Social Performance (PSP) scale (3.1 points) over the 3-year period. 

No unexpected side effects

“No new safety concerns outside the adverse event (AE) profile of the drug were identified, and no deaths were reported,” the investigators said, adding that the 3-year AE profile of every-6-months dosing of paliperidone palmitate was consistent with its known profile.

The overall rate of treatment-emergent AEs (TEAEs) was 80.2 percent, of which 53.7 percent were TEAEs deemed possibly related to treatment. Headache (18.2 percent) and weight gain (12.4 percent) were the most common TEAEs, followed by blood prolactin elevation (11.6 percent), nasopharyngitis (10.7 percent), injection site pain (10.7 percent), diarrhoea (8.3 percent), and hyperprolactinemia (7.4 percent), among others. Most of these events were mild to moderate in severity.

Serious TEAEs occurred in 5.8 percent of patients, including schizophrenia, depression, psychiatric symptom, colon cancer, cancer metastases to peritoneum, and nephrotic syndrome. The rate of TEAEs leading to study withdrawal was 5.0 percent.

A total of 121 patients (mean age 38.6 years, 31.4 percent female, mean illness duration 11.0 years) were included in the 3-year intention-to-treat analysis. They received paliperidone palmitate at 1,092 mg (700-mg equivalent of paliperidone; 3.5 mL) or 1,560 mg (1,000-mg equivalent of paliperidone; 5.0 mL), administered every 6 months in prefilled syringes, with flexible dosing allowed during the OLE study. Mean dose of paliperidone palmitate every 6 months was 1,367.7 mg (876.7-mg equivalent of paliperidone).

At baseline, 83.5 percent of patients were taking an oral antipsychotic and 16.5 percent were taking an LAI antipsychotic (injectable risperidone, paliperidone palmitate once monthly or every 3 months). The median observation time was 3.0 years.

Schizophrenia recovery

“Recovery, [defined as] the combination of symptomatic remission and adequate psychosocial and educational or vocational functioning, is an established goal of treatment in adults with schizophrenia and usually involves integration of pharmacologic and psychologic approaches,” the investigators said. 

“The low rate of relapse reported in this study highlights … that LAI antipsychotics … can facilitate and support the recovery process. In this regard, treatments such as paliperidone palmitate every 6 months can play a potentially important role in long-term recovery in patients with schizophrenia,” they added.

LAI antipsychotics are considered an effective tool for managing schizophrenia in adults, even though they may not work for everyone. Compared with oral antipsychotics, the injectable formulation offers a significant advantage in reducing relapse, hospital stays, treatment dropout, work problems, and even death. In fact, a recent Delphi panel studying LAI antipsychotics in early schizophrenia suggests that all patients undergo an assessment to determine their suitability for this treatment. [Lancet Psychiatry 2020;7:749-761; Schizophr Bull 2021;47:1611-1620; Am J Psychiatry 2022;179:938-946; Lancet Psychiatry 2021;8:387-404; BMC Psychiatry 2023;23:453]

“The longer dosing intervals associated with LAI antipsychotics contribute to clinical stability, providing potential for long-term improvements in functionality, social integration, and patient empowerment,” the investigators explained. “Furthermore, LAI antipsychotic treatment in combination with nonpsychopharmacologic treatment strategies may encourage personal recovery beyond the framework of traditional outcome measures and mental health services.”

The OLE study had several limitations, including the lack of a comparator group, the potential for effects of confounding demographic factors on data due to the small number of countries that participated, and the inclusion of patients who were clinically stable that may preclude generalizability to the broader study population, among others.