FDA Approves Risperidone Injection for Bipolar I Disorder in Adults

The FDA approved risperidone (Uzedy) as a once monthly extended-release injectional suspension as monotherapy or adjunctive therapy to lithium or valproate for the maintenance treatment of bipolar I disorder (BD-I) in adults.¹

“Adults living with BD-I experience debilitating manic and depressive symptoms, and today’s FDA approval of Uzedy provides a new long-acting formulation of risperidone that may help address existing unmet needs and treatment gaps,” Chris Fox, executive vice president of US Commercial at Teva, said in a news release.¹ “This expanded indication for Uzedy builds on its success in adults living with schizophrenia and demonstrates Teva’s dedication to developing innovative medicines for complex mental health conditions that place a heavy burden on individuals and their caregivers.”

The approval was based on clinical data of risperidone as well as model-informed drug development methodologies that support previous safety and efficacy of risperidone formulations already approved for BD-I. The data were part of the safety and efficacy of the TV46000-CNS-30072 (the RISE Study—The Risperidone Subcutaneous Extended-Release Study) and TV46000-CNS-30078 (the SHINE Study—Safety in Humans of TV-46000 sc INjection Evaluation) phase 3 studies, which were used to determine the treatment of schizophrenia.¹

In the RISE (NCT03503318) study, there were 2 treatment stages, which included the 2-week open-label stabilization phase with the oral formulation of the drug and the open-ended randomized double-blind study with the subcutaneous formulation. Patients in the study were diagnosed with schizophrenia more than 1 year prior to screening and had at least 1 relapse in the 24 months prior to eligibility. Investigators included 183 patients who received the subcutaneous formulation once monthly, 180 who received the subcutaneous formulation twice monthly, and 181 who received the placebo.²

Compared with the placebo, the time to impending relapse was prolonged by 5 times and 2.7 times with the once monthly and twice monthly subcutaneous injections, respectively. As for adverse events (AEs), the most frequently reported for both treatment groups compared with the placebo group included injection site nodules, weight increase, and extrapyramidal disorder. Nine patients in the once monthly group, 10 patients in the twice monthly group, and 14 patients in the placebo group experienced serious AEs.²

For the SHINE (NCT03893825) study, patients who completed the RISE trial without relapse were included as well as patients who were newly recruited. Patients who received the placebo in RISE or were new to the study received either the once monthly or twice monthly injection 1:1 up to 56 weeks. Approximately 37% and 46% of patients on the once monthly and twice monthly injections, respectively, experienced 1 AE or more, and 21% and 20% experienced 1 or more treatment-related AEs. The most common were injection site pain and injection site nodules, according to the investigators.³

“Bipolar I disorder carries profound implications for a person’s life and is linked to suboptimal long-term outcomes, with treatment adherence to daily oral options frequently presenting as a major impediment to effective care,” Craig Chepke, MD, DFAPA, medical director of Excel Psychiatric Associates, said in a news release. “The FDA’s decision to expand the indication for Uzedy may help those living with BD-I. As a clinician, I am excited to now have a new treatment option for this complex disease.”

READ MORE: Mental and Behavioral Health Resource Center

Are you ready to elevate your pharmacy practice? Sign up today for our free Drug Topics newsletter and get the latest drug information, industry trends, and patient care tips straight to your inbox.

REFERENCES

1. FDA approves expanded indication for Uzedy (risperidone) extended-release injectable suspension as a treatment for adults living with bipolar I disorder. News release. Teva. October 10, 2025. Accessed October 14, 2025. https://www.tevapharm.com/news-and-media/latest-news/fda-approves-expanded-indication-for-uzedy-risperidone-extended-release-injectable-suspension-as-a-tre/

2. Kane JM, Harary E, Eshet R, et al. Efficacy and safety of TV-46000, a long-acting, subcutaneous, injectable formulation of risperidone, for schizophrenia: a randomised clinical trial in the USA and Bulgaria. Lancet Psychiatry. 2023;10(12):934-943. doi:10.1016/S2215-0366(23)00288-2

3. Kane JM, Eshet R, Harary E, et al. A Long-Term Safety and Tolerability Study of TV-46000 for Subcutaneous Use in Patients with Schizophrenia: A Phase 3, Randomized, Double-Blinded Clinical Trial. CNS Drugs. 2024;38(8):625-636. doi:10.1007/s40263-024-01102-2