Comparative Outcomes of TV-46000 and Paliperidone Palmitate in Schizophrenia: Evidence From Clinical, Pharmacokinetic, and Safety Studies

Schizophrenia is a chronic psychiatric disorder with a high risk of relapse, often complicated by poor adherence to oral antipsychotics.¹ Long-acting injectable (LAI) formulations improve adherence and reduce hospitalization rates.^1,2 Paliperidone palmitate once monthly (PP1m) is another treatment option that requires a 2-dose initiation regimen, which may prolong hospital stays. TV-46000, a subcutaneous risperidone LAI, allows simplified initiation with dosing every 1 or 2 months.² This review synthesizes recent clinical and modeling data comparing TV-46000 with PP1m. 

Four recent investigations provide insight into clinical, safety, pharmacokinetic, and comparative outcomes when evaluating TV-46000 against PP1m. 

In a retrospective survey presented at the Annual Psych Congress, initiation of TV-46000 during hospitalization was associated with a significantly shorter mean length of stay (LOS) compared with PP1m (12.57 vs 15.46 days; P = .033). HCPs favored TV-46000 for ease of initiation and administration, though PP1m was rated higher for perceived onset of action. The authors concluded: “Patients initiated on TV-46000 during their hospitalization had a shorter mean LOS (from LAI initiation to hospital discharge) compared with those initiated on PP1m.”²  

In the pooled analysis of the RISE and SHINE studies, some of the most common adverse events were headache, insomnia, akathisia, weight gain, and hyperglycemia, each occurring in ≤6% of participants. No cardiovascular adverse events occurred in ≥2% of participants. The only consistent laboratory finding was prolactin elevation. Overall, the safety profile was favorable and consistent with other risperidone formulations.³

PopPK modeling demonstrated that switching from PP1m 234 mg to TV-46000 125 mg once monthly, initiated 4 weeks after the last PP1m injection, resulted in comparable steady-state exposures. Similar equivalence was observed across other PP1m and TV-46000 dosing regimens. These results support flexible switching strategies guided by clinical judgment and patient-specific needs.⁴  

A systematic literature review and network meta-analysis (NMA) of randomized controlled trials found that TV-46000 provided relapse prevention efficacy comparable to PP1m and other second-generation LAIs. Weight gain ≥7% was less frequent with TV-46000 (q1m or q2m) compared with higher-dose PP1m and PP3m. Injection-site tolerability did not differ significantly between agents.¹ 

Collectively, these investigations suggest that TV-46000 is a clinically meaningful alternative to PP1m. Its simplified initiation regimen was associated with shorter inpatient stays, potentially reducing health care resource use.² Safety outcomes were consistent with other risperidone formulations, with prolactin elevation the only consistent laboratory signal.³ Pharmacokinetic modeling indicates that switching between PP1m and TV-46000 can be achieved without major disruption to drug exposure.⁴ Finally, comparative analyses suggest equivalent efficacy with a potential advantage in weight-related tolerability.¹  

Limitations should be noted. The LOS and HCP preference data are from a retrospective survey rather than a randomized trial.² The pharmacokinetic analysis was simulation-based rather than clinical.⁴ The NMA included a limited number of studies.¹ These factors highlight the need for confirmatory prospective studies. 

TV-46000 demonstrates efficacy and safety comparable to PP1m, with practical advantages including simplified initiation, reduced inpatient LOS, and potentially improved metabolic tolerability. These findings support its role as a competitive second-generation LAI option for the treatment of schizophrenia. 

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2. Franzenburg K R, Hansen R, Suett M, et al. Efficacy and safety of TV-46000 and second-generation long-acting injectable antipsychotics for schizophrenia: a systematic literature review and network meta-analysis of randomized controlled trials. Adv Ther. 2025;42:4188-4209. doi:10.1007/s12325-025-03274-9 
3. Patel A, Phatak A, Hansen R T, et al. Inpatient length of stay and healthcare professional preferences for initiating TV-46000, a long-acting subcutaneous antipsychotic, or intramuscular paliperidone palmitate in patients hospitalized with schizophrenia. Presented at: Annual Psych Congress; September 17-21, 2025; San Diego, CA.  
4. Correll CU, Knebel H, Harary E, et al. Safety outcomes with the long-acting subcutaneous antipsychotic TV-46000 in schizophrenia: a post hoc analysis of behavioral, neuromotor, endocrine, and cardiometabolic outcomes from two phase 3 studies. CNS Drugs. 2025. doi:10.1007/s40263-025-01197-1 
5. Perlstein I, Meyer J, Yue Z, et al. Switching patients with schizophrenia from intramuscular paliperidone palmitate once monthly to TV-46000, a long-acting subcutaneous antipsychotic: population pharmacokinetic–based strategies. Adv Ther. 2025. doi:10.1007/s12325-025-03329-x 
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