Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Sep;42(9):4188-4209.
doi: 10.1007/s12325-025-03274-9. Epub 2025 Jul 16.

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

Kelli R Franzenburg  1 , Rolf Hansen  2 , Mark Suett  3 , Stephen F Thompson  4 , Martin Sergerie  5 , David Garcia  6 , Howard C Margolese  7
Affiliations

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

Kelli R Franzenburg et al. Adv Ther. 2025 Sep.

Abstract

Introduction: TV-46000 [once monthly (q1m) or once every 2 months (q2m)] is a subcutaneously administered long-acting injectable antipsychotic (LAI) formulation of risperidone for the treatment of schizophrenia in adults. As second-generation LAIs become available, understanding comparative efficacy and safety is needed.

Methods: We undertook a systematic literature review (SLR; January 1, 2020 to May 11, 2023) and network meta-analyses (NMAs) of randomized controlled clinical trials to compare the efficacy and safety of TV-46000 q1m and q2m with second-generation LAIs approved in Canada and used for treatment of schizophrenia [intramuscular aripiprazole monohydrate q1m, paliperidone palmitate q1m (PP1M), and paliperidone palmitate once every 3 months (PP3M)]. The primary efficacy outcome was relapse rate at 6 months, while safety outcomes were adverse event (AE)-related discontinuation, significant weight gain (≥ 7%), treatment-related AEs, and injection-site pain.

Results: Sixty-one records from 24 studies were included in the SLR, and 6 were included in the NMAs. For the relapse rate at 6 months, all treatments were significantly better than placebo, with relative risks (RRs) ranging from 0.23 for TV-46000 q1m to 0.46 for PP1M 50-150 mg eq and no significant differences among LAIs. There were no significant differences between TV-46000 and either placebo or PP1M 25-100 mg eq for AE-related discontinuation. TV-46000 q1m, PP1M 25-100 mg eq, and TV-46000 q2m were significantly less likely to cause weight gain ≥ 7% than PP3M (RR: 0.09, 0.09, and 0.06, respectively) or PP1M 50-150 mg eq (0.08, 0.08, and 0.06, respectively). Treatment-related AEs were significantly less likely with PP1M 25-100 mg eq, TV-46000 q1m, and placebo than PP3M (RR: 0.48, 0.62, and 0.66, respectively). There were no significant differences in injection-site pain between groups.

Conclusion: TV-46000 q1m and q2m demonstrated comparable efficacy and safety to second-generation LAIs approved in Canada and used for maintenance treatment of schizophrenia.

Keywords: Canada; Long-acting injectable antipsychotic; Network meta-analysis; Schizophrenia; Systematic literature review; TV-46000.

Plain language summary

Injectable drugs that work for long periods of time have successfully been used to treat schizophrenia. TV-46000 is injected under the skin once monthly or once every 2 months. It is approved in the United States to treat schizophrenia in adults. When new medications become available, doctors need to understand the safety of that medication and how well it treats the symptoms of the disease compared with similar medications. We searched for studies that used injectable medication approved in Canada and used for the long-term treatment of schizophrenia. We used the results from our search to compare TV-46000 with medications in our search. To study how well the medications treated the disease, we looked at how many patients had a relapse of symptoms by 6 months on the medication. For safety, we looked at: (1) how many patients left the studies because of side effects, (2) if the medication caused weight increase, (3) other side effects experienced, and (4) pain at the injection site. All the medications we looked at were better than placebo (inactive injections) at reducing the number of patients who had a relapse at 6 months. TV-46000 injected every month or every 2 months showed the same safety results as placebo injections. This analysis showed that TV-46000 generally had the same safety and ability to treat symptoms as other injectable medications approved in Canada and used for the long-term treatment of schizophrenia.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflicts of Interest: Kelli R. Franzenburg, Rolf Hansen, Mark Suett, Stephen F. Thompson, and Martin Sergerie are employees and shareholders of Teva Pharmaceuticals. David Garcia is an employee of EVERSANA, which provides commercialization services to the life sciences industry. Teva Pharmaceuticals contracted EVERSANA to complete this SLR and NMA. Howard C. Margolese received research grant support from AIFred, SyneuRx, and The Montreal General Hospital Foundation; speaker/consultation/ad board fees from AbbVie, Bausch Health, Boehringer Ingelheim, HLS Therapeutics, Lundbeck, Janssen, Newron, Otsuka, and Teva Pharmaceuticals. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants performed by any of the authors. Open Access: This article is licensed under a Creative Commons Attribution—Non-Commercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third-party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative. Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view.a copy of this license, visit http://creativecommons.org/licenses/by-nc/4.0/ .

Figures

Fig. 1
Fig. 1
PRISMA diagram. MA meta-analysis, NMA network meta-analysis, PRISMA Preferred Reporting Items for Systematic Reviews and Meta-Analyses, SLR systematic literature review
Fig. 2
Fig. 2
Fixed-effects NMA league tables. a Relapse rate at 6 months (average population). b Time to relapse. c Change in personal and social performance. d Adverse event-related discontinuation at 26 weeks. e Significant weight gain (≥ 7%) at 26 weeks. f Treatment-related adverse events at 26 weeks. g Injection-site pain. Pairwise comparisons from the fixed-effect model are shown in terms of relative risk (a, d, e, f, g) or hazard ratio (b) and 95% credible intervals (CrIs). Order on the table is determined by the average rank of a treatment. Treatments with the highest rank are found at the top left side of the table. Comparisons should be read from top to bottom (e.g., TV-46000 q1m vs. placebo), and each estimate is listed in the cell in common between the column-defining treatment and the row-defining treatment. Rank is determined by point estimates and does not indicate certainty of superiority or inferiority. A CrI overlapping 1 is indicative of treatments that are comparable (gray cells). A CrI that does not contain 1 indicates that there are significant differences between treatments (pink cells). For example, in a, the relative risk of 0.23 for TV-46000 q1m (column-defining treatment) compared to placebo (row-defining treatment) indicates that TV-46000 q1m is associated with a 77% significant reduction in the risk of relapse at 6 months compared to placebo. c Pairwise comparisons from the fixed-effect model are shown in terms of mean difference and 95% credible intervals (CrIs). Order on the table is determined by the average rank of a treatment. Treatments with the highest rank are found at the top left side of the table. Rank is determined by point estimates and does not indicate certainty of superiority or inferiority. A CrI that contains 0 is indicative of treatments that are comparable (gray cells). A CrI that does not contain 0 indicates that there are significant differences between treatments (pink cells). Model specifications: b, c, f 40,000 iterations, 40,000 burn-ins, 1 thinning. d, e 80,000 iterations, 40,000 burn-ins, 2 thinning. g 200,000 iterations, 100,000 burn-ins, 5 thinning. PP1M paliperidone palmitate 1-month, PP3M paliperidone palmitate 3-month, q1m monthly, q2m bi-monthly
Fig. 2
Fig. 2
Fixed-effects NMA league tables. a Relapse rate at 6 months (average population). b Time to relapse. c Change in personal and social performance. d Adverse event-related discontinuation at 26 weeks. e Significant weight gain (≥ 7%) at 26 weeks. f Treatment-related adverse events at 26 weeks. g Injection-site pain. Pairwise comparisons from the fixed-effect model are shown in terms of relative risk (a, d, e, f, g) or hazard ratio (b) and 95% credible intervals (CrIs). Order on the table is determined by the average rank of a treatment. Treatments with the highest rank are found at the top left side of the table. Comparisons should be read from top to bottom (e.g., TV-46000 q1m vs. placebo), and each estimate is listed in the cell in common between the column-defining treatment and the row-defining treatment. Rank is determined by point estimates and does not indicate certainty of superiority or inferiority. A CrI overlapping 1 is indicative of treatments that are comparable (gray cells). A CrI that does not contain 1 indicates that there are significant differences between treatments (pink cells). For example, in a, the relative risk of 0.23 for TV-46000 q1m (column-defining treatment) compared to placebo (row-defining treatment) indicates that TV-46000 q1m is associated with a 77% significant reduction in the risk of relapse at 6 months compared to placebo. c Pairwise comparisons from the fixed-effect model are shown in terms of mean difference and 95% credible intervals (CrIs). Order on the table is determined by the average rank of a treatment. Treatments with the highest rank are found at the top left side of the table. Rank is determined by point estimates and does not indicate certainty of superiority or inferiority. A CrI that contains 0 is indicative of treatments that are comparable (gray cells). A CrI that does not contain 0 indicates that there are significant differences between treatments (pink cells). Model specifications: b, c, f 40,000 iterations, 40,000 burn-ins, 1 thinning. d, e 80,000 iterations, 40,000 burn-ins, 2 thinning. g 200,000 iterations, 100,000 burn-ins, 5 thinning. PP1M paliperidone palmitate 1-month, PP3M paliperidone palmitate 3-month, q1m monthly, q2m bi-monthly
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th Edition. Arlington, VA: American Psychiatric Association; 2013.
    1. Kahn RS, Sommer IE, Murray RM, et al. Schizophrenia. Nat Rev Dis Primers. 2015;1:15067. - PubMed
    1. Lieberman JA, Malaspina D, Jarskog LF. Preventing clinical deterioration in the course of schizophrenia: the potential for neuroprotection. CNS Spectr. 2006;11(4):1–13. - PubMed
    1. Lin D, Thompson-Leduc P, Ghelerter I, et al. Real-world evidence of the clinical and economic impact of long-acting injectable versus oral antipsychotics among patients with schizophrenia in the United States: a systematic review and meta-analysis. CNS Drugs. 2021;35(5):469–81. - PMC - PubMed
    1. Patel RS, Tankersley WE. Real-world effectiveness of long-acting injectable antipsychotics to reduce 90-day and annual readmission in psychotic disorders: insights from a state psychiatric hospital. CNS Spectr. 2022;27(5):626–33. - PubMed

Publication types

MeSH terms