Paliperidone 6-month LAI sustains symptomatic, functional remission in schizophrenia at 3 years

Patients with schizophrenia who either continued on the long-acting injectable (LAI) paliperidone palmitate 6-monthly (PP6M) for up to 3 years or transitioned from PP 3-monthly (PP3M) treatment have sustained symptomatic and functional remission, as shown in a post hoc analysis of the single-arm, open-label extension (OLE) study PSY3016.

“Our findings suggest that symptomatic and functional remission are achievable outcomes in a considerable proportion of patients receiving PP6M or transitioning from PP3M to PP6M over a 3-year period,” said lead author Professor Joshua Hamilton, a psychiatric nurse practitioner at the Washington State University College of Nursing, Spokane, Washington, US.

Adopting the definition of symptomatic remission as no more than mild symptoms on eight predefined items on the Positive and Negative Syndrome Scale (PANSS) for ≥6 months, 85.1 percent of patients who received PP6M through the parent 12-month, double-blind (DB), randomized Route 6 study and the 2-year OLE (PP6M/PP6M) met the criteria for remission at 1 year. Continued treatment sustained the remission rate at 86.1 percent by the end of 3 years.

In patients randomized to receive DB PP3M during the 1-year Route 6 study and who continued treatment with PP6M upon entering study PSY3016 (PP3M/PP6M), the rate of achieving symptomatic remission was 82.5 percent at the time of treatment transition. The remission rate was maintained at 81.1 percent after 2 years of PP6M treatment. [Neuropsychiatr Dis Treat 2025:21:1203-1214]

“The rates of symptomatic remission (>80 percent) observed in this analysis were notably higher than those reported in earlier studies using the same PANSS-based definition across different subpopulations,” said Hamilton. “These findings are likely attributed to factors related to PP-LAIs such as stable antipsychotic plasma levels, improved adherence from reduced dosing frequency, and enhanced treatment continuity.”

Improvement in social functioning, assessed as functional remission in the current analysis, was demonstrated at 1 year in 55.4 percent of PP6M/PP6M patients. The remission rate was maintained with an observed increase to 58.8 percent at 3 years. Similarly, 52.6 percent and 58.5 percent of patients in the PP3M/PP6M group attained functional remission at 1 year and 3 years, respectively.

“The current study demonstrates that a high proportion of patients achieved remission in psychosocial and other functional domains with continuous PP6M treatment,” said Hamilton. “These results are clinically meaningful, with significant implications for improved daily functioning, social interactions, and potentially maximizing the chances of recovery for patients with schizophrenia.”

Relapse-free adults

Study PSY3016 enrolled participants from the parent phase III Route 6 study who remained relapse-free after completing the 12-month DB treatment and chose to continue treatment with PP6M. Of the 702 adult patients randomized in Route 6, 178 participated in study PSY3016. [Int J Neuropsychopharmacol 2023;26:537-544]

The eight items on PANSS covered in the definition of symptomatic remission include three positive-symptom items (P1, P2, and P3), three negative-symptom items (N1, N4, and N6), and two general-psychopathology items (G5 and G9). The current remission analysis focused on patients who had scores ≤3 on all eight items simultaneously for ≥6 months, allowing one excursion. [Am J Psychiatry 2005;162:441-449]

In defining functional remission, the Personal and Social Performance scale was adopted, with a cutoff score >70 at all assessment timepoints designated as remission. [Acta Psychiatr Scand 2000;101:323-329]

“Taken together, these findings on remission contribute to the growing body of evidence supporting the effectiveness of PP-LAIs in reducing relapses and treatment failures in schizophrenia,” Hamilton concluded.