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
Bibliographic record
Abstract
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. 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. 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. TV-46000 q1m and q2m demonstrated comparable efficacy and safety to second-generation LAIs approved in Canada and used for maintenance treatment of schizophrenia. 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.009 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.036 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".