Dataset Information

The role of lumateperone in the treatment of schizophrenia.

ABSTRACT: Schizophrenia is a devastating mental disorder resulting in marked morbidity and mortality despite the optimal use of all currently available interventions. For this reason, the release of lumateperone (Captyla^R), also known as ITI-007, an orally administered, atypical antipsychotic provided a welcome novel tool for clinicians to utilize precision medicine to tailor an optimal treatment plan to the specific needs of each person with schizophrenia. To generate a foundation for clinicians to assess the risks and benefits of lumateperone in relation to other interventions for schizophrenia, we conducted a search of items for 'ITI-007' and 'lumateperone' on PubMed, ScienceDirect, Web of Science, Google Scholar, and www.clinicaltrials.gov. We present a critical evaluation of the limited information about lumateperone for schizophrenia, its use approved by the US Food and Drug Administration. Lumateperone merits consideration for patients with treatment-resistant schizophrenia and for patients with schizophrenia who are vulnerable to developing metabolic dysfunction and movement disorders. On the other hand, lumateperone should not be used for (a) women who are pregnant or breastfeeding, children, adolescents, and elderly patients with dementia-related psychosis, (b) patients who are at risk for cerebrovascular diseases, (c) patients who use inducers and moderate or strong inhibitors of the cytochrome P450-3A4 (CYP3A4) isozyme, and (d) patients who use alcohol and other sedating agents. Clinical trials from multiple centers without financial conflicts of interest to market lumateperone are needed to directly compare and contrast lumateperone and other antipsychotic agents to generate trustworthy evidence to be assessed objectively by clinicians treating patients with schizophrenia. Future investigations will provide the foundations to identify the evidence for comprehensive evaluations of the role of lumateperone in the treatment of people with schizophrenia and other conditions.

SUBMITTER: Syed AB

PROVIDER: S-EPMC8326816 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ImportanceIndividuals living with schizophrenia are affected by cardiometabolic, endocrine, and motor adverse effects of current antipsychotic medications. Lumateperone is a serotonin, dopamine, and glutamate modulator with the potential to treat schizophrenia with few adverse effects.ObjectiveTo examine the efficacy and safety of lumateperone for the short-term treatment of schizophrenia.Design, setting, and participantsThis randomized, double-blind, placebo-controlled, phase 3 clinical trial was conducted from November 13, 2014, to July 20, 2015, with data analyses performed from August 13 to September 15, 2015. Patients with schizophrenia who were aged 18 to 60 years and were experiencing an acute exacerbation of psychosis were enrolled from 12 clinical sites in the United States.InterventionsPatients were randomized 1:1:1 (150 patients in each arm) to receive lumateperone tosylate, 60 mg; lumateperone tosylate, 40 mg (equivalent to 42 or 28 mg, respectively, of the active moiety lumateperone); or placebo once daily for 4 weeks.Main outcomes and measuresThe prespecified primary efficacy end point was mean change from baseline to day 28 in the Positive and Negative Syndrome Scale (PANSS) total score vs placebo. The key secondary efficacy measure was the Clinical Global Impression-Severity of Illness (CGI-S) score. The PANSS subscale scores, social function, safety, and tolerability were also assessed.ResultsThe study comprised 450 patients (mean [SD] age, 42.4 [10.2] years; 346 [77.1%] male; mean [SD] baseline PANSS score, 89.8 [10.3]; mean [SD] baseline CGI-S score, 4.8 [0.6]). In the prespecified modified intent-to-treat efficacy analysis (n = 435), 42 mg of lumateperone met the primary and key secondary efficacy objectives, demonstrating a statistically significant improvement vs placebo from baseline to day 28 on the PANSS total score (least-squares mean difference [LSMD], -4.2; 95% CI, -7.8 to -0.6; P = .02; effect size [ES], -0.3) and the CGI-S (LSMD, -0.3; 95% CI, -0.5 to -0.1; P = .003; ES, -0.4). For 28 mg of lumateperone, the LSMD from baseline to day 28 was -2.6 (95% CI, -6.2 to 1.1; P = .16; ES, -0.2) on the PANSS total score and -0.2 (95% CI, -0.5 to 0.0; P = .02; ES, -0.3) on the CGI-S. Both lumateperone doses were well tolerated without clinically significant treatment-emergent motor adverse effects or changes in cardiometabolic or endocrine factors vs placebo.Conclusions and relevanceLumateperone demonstrated efficacy for improving the symptoms of schizophrenia and had a favorable safety profile.Trial registrationClinicalTrials.gov identifier: NCT02282761.

Project description:Background: Inflammation plays a major role in the onset and maintenance of schizophrenia. The objective of the present work was to synthetize in a narrative review the recent findings in the field of inflammation in schizophrenia and their application in daily practice. Method: This review was based on the most recent meta-analyses and randomized controlled trials. Results: The disturbed cytokines depend on the phase of the illness. A meta-analysis of cytokines in schizophrenia found higher levels of pro-inflammatory and anti-inflammatory cytokines in the peripheral blood in both patients with first-episode schizophrenia and relapsed patients than in healthy controls. Exploring detailed data on immune-inflammatory disturbances in SZ reveals that IL-6 is one of the most consistently disturbed cytokines. Other cytokines, including IL1, TNF, and IFN, are also disturbed in schizophrenia. Choosing a broad spectrum anti-inflammatory agent that may inhibit subsequent pathways might be particularly useful for the treatment of inflammatory schizophrenia. Highly sensitive C-Reactive Protein is a useful screening marker for detecting inflammation in SZ subjects. Anti-inflammatory agents have shown effectiveness in recently published meta-analyses. Only one study found a significant difference between celecoxib and placebo, but two found a trend toward significance on illness severity and one on positive symptoms. In addition, other published and unpublished data were included in another meta-analysis that concluded the significant effect of add-on celecoxib in positive symptoms in first episode patients. There is a lack of data to determine if aspirin is truly effective in schizophrenia to date. Other anti-inflammatory agents have been explored, including hormonal therapies, antioxidants, omega 3 fatty acids, and minocycline, showing significant effects for reducing total, positive, and negative score symptoms and general functioning. However, each of these agents has multiple properties beyond inflammation and it remains unclear how these drugs improve schizophrenia. Conclusion: The next step is to tailor anti-inflammatory therapy in schizophrenia, with two main challenges: 1. To provide a more efficient anti-inflammatory therapeutic approach that targets specific pathways associated with the pathology of schizophrenia. 2. To develop a more personalized approach in targeting patients who have the best chance of successful treatment.

Dataset Information

The role of lumateperone in the treatment of schizophrenia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets