Treatment continuation and factors associated with discontinuation with 3-month paliperidone palmitate in patients with schizophrenia: a post hoc analysis of post-marketing surveillance data in Japan

Introduction Schizophrenia requires sustained treatment to prevent relapse and maintain functional stability. Poor adherence to oral antipsychotics is common and increases the risk of relapse and rehospitalization. Long-acting injectable antipsychotics, such as paliperidone palmitate 3-month formulation (PP3M), have been developed to improve adherence and clinical outcomes; however, evidence on clinical factors influencing treatment continuation and concomitant medication use in real-world settings remains limited. This post hoc analysis explored treatment continuation and its associated factors in Japanese patients with schizophrenia receiving PP3M, including reasons for discontinuation, mortality, and changes in concomitant medications. Methods Data from a multicenter, prospective post-marketing surveillance in Japan were used. Patients stabilized on paliperidone palmitate 1-month formulation for ≥4 months were transitioned to PP3M. Treatment continuation was assessed using Kaplan–Meier analysis, and factors associated with discontinuation were evaluated using multivariable Cox regression analysis. Mortality rates and treatment-related standardized mortality ratios (SMRs) were calculated, and concomitant medication patterns were analyzed descriptively. Results A total of 891 patients were included. The previously reported 12-month treatment continuation rate was 84.7%. Patients without concomitant medications had significantly higher continuation rates than those with concomitant medications (85.3% versus 76.8%, P = 0.001). The lowest starting dose of PP3M (175 mg) was a significant risk factor for discontinuation (hazard ratio 1.90, 95% confidence interval [CI] 1.12, 3.21). The treatment-related mortality was 3.94 per 1,000 person-years (95% CI 1.07, 10.09). The treatment-related SMR for the total population was 0.95 (95% CI 0.02, 1.89). Concomitant medication and benzodiazepine equivalent dose remained stable (treatment start, 35.79 mg; treatment end, 35.94 mg). Conclusions PP3M demonstrated high treatment continuation in Japanese patients with schizophrenia, particularly those without concomitant medications. The lowest PP3M starting dose of 175 mg was associated with an increased risk of treatment discontinuation, underscoring the importance of individualized dosing strategies. Stable concomitant medication use supports symptomatic stability and the feasibility of PP3M monotherapy. These findings highlight the potential of PP3M to reduce pharmacologic burden and support long-term management of schizophrenia. Clinical trial registration https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000047973 , identifier UMIN000042033