{"title":"lumateperone治疗双相抑郁症的剂量反应疗效和安全性:随机对照试验的初步荟萃分析。","authors":"Chih-Wei Hsu, Yu-Kang Tu, Kuo-Chuan Hung, Chih-Sung Liang, Ping-Tao Tseng, Yang-Chieh Brian Chen","doi":"10.1177/02698811251364389","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The optimal lumateperone dose for bipolar depression remains uncertain.</p><p><strong>Aims: </strong>To examine its dose-response relationship for efficacy and safety.</p><p><strong>Methods: </strong>We systematically searched major databases to 1 July 2025. Efficacy outcomes included change in depression severity, global illness severity, quality of life, responder, and remitter rates. Safety outcomes included all-cause dropout, discontinuations due to adverse event (AE), treatment-emergent AE, mania, suicidality, extrapyramidal symptoms, body weight, lipid profile, and fasting glucose. A one-step dose-response meta-analysis generated effect sizes, reported as standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Three randomized controlled trials involving 1454 patients showed that a 42-mg daily dose of lumateperone significantly improved depressive symptoms (SMD = -0.26; 95% CI: -0.51, -0.02), Clinical Global Impression-Bipolar-Severity (CGI-BP-S) overall bipolar illness (SMD = -0.31; 95% CI: -0.45, -0.16), CGI-BP-S bipolar depression (SMD = -0.33; 95% CI: -0.48, -0.17), quality of life (SMD = 0.22; 95% CI: 0.07, 0.36), and responder rate (RR = 1.27; 95% CI: 1.05, 1.53), but not remitter rate (1.06; 95% CI: 0.81, 1.38). Compared with placebo, discontinuation due to AE significantly increased at the 42 mg dose (RR = 3.12; 95% CI: 1.68, 5.80), but not at 28 mg (1.58; 95% CI: 0.25, 9.89). Moreover, dropout rates (42 mg RR = 1.15; 95% CI: 0.76, 1.73) and other safety outcomes did not exhibit a dose-response trend.</p><p><strong>Conclusions: </strong>Preliminary evidence suggests that 42 mg daily of lumateperone may provide clinical benefit in bipolar depression, yet the higher rate of AE-related discontinuation warrants caution in practice. However, current data remain limited, requiring further studies to establish the optimal dosing range balancing efficacy and safety.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251364389"},"PeriodicalIF":5.5000,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dose-response efficacy and safety of lumateperone in bipolar depression: A preliminary meta-analysis of randomized controlled trials.\",\"authors\":\"Chih-Wei Hsu, Yu-Kang Tu, Kuo-Chuan Hung, Chih-Sung Liang, Ping-Tao Tseng, Yang-Chieh Brian Chen\",\"doi\":\"10.1177/02698811251364389\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The optimal lumateperone dose for bipolar depression remains uncertain.</p><p><strong>Aims: </strong>To examine its dose-response relationship for efficacy and safety.</p><p><strong>Methods: </strong>We systematically searched major databases to 1 July 2025. Efficacy outcomes included change in depression severity, global illness severity, quality of life, responder, and remitter rates. Safety outcomes included all-cause dropout, discontinuations due to adverse event (AE), treatment-emergent AE, mania, suicidality, extrapyramidal symptoms, body weight, lipid profile, and fasting glucose. A one-step dose-response meta-analysis generated effect sizes, reported as standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>Three randomized controlled trials involving 1454 patients showed that a 42-mg daily dose of lumateperone significantly improved depressive symptoms (SMD = -0.26; 95% CI: -0.51, -0.02), Clinical Global Impression-Bipolar-Severity (CGI-BP-S) overall bipolar illness (SMD = -0.31; 95% CI: -0.45, -0.16), CGI-BP-S bipolar depression (SMD = -0.33; 95% CI: -0.48, -0.17), quality of life (SMD = 0.22; 95% CI: 0.07, 0.36), and responder rate (RR = 1.27; 95% CI: 1.05, 1.53), but not remitter rate (1.06; 95% CI: 0.81, 1.38). Compared with placebo, discontinuation due to AE significantly increased at the 42 mg dose (RR = 3.12; 95% CI: 1.68, 5.80), but not at 28 mg (1.58; 95% CI: 0.25, 9.89). Moreover, dropout rates (42 mg RR = 1.15; 95% CI: 0.76, 1.73) and other safety outcomes did not exhibit a dose-response trend.</p><p><strong>Conclusions: </strong>Preliminary evidence suggests that 42 mg daily of lumateperone may provide clinical benefit in bipolar depression, yet the higher rate of AE-related discontinuation warrants caution in practice. However, current data remain limited, requiring further studies to establish the optimal dosing range balancing efficacy and safety.</p>\",\"PeriodicalId\":16892,\"journal\":{\"name\":\"Journal of Psychopharmacology\",\"volume\":\" \",\"pages\":\"2698811251364389\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2025-08-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Psychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/02698811251364389\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/02698811251364389","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Dose-response efficacy and safety of lumateperone in bipolar depression: A preliminary meta-analysis of randomized controlled trials.
Background: The optimal lumateperone dose for bipolar depression remains uncertain.
Aims: To examine its dose-response relationship for efficacy and safety.
Methods: We systematically searched major databases to 1 July 2025. Efficacy outcomes included change in depression severity, global illness severity, quality of life, responder, and remitter rates. Safety outcomes included all-cause dropout, discontinuations due to adverse event (AE), treatment-emergent AE, mania, suicidality, extrapyramidal symptoms, body weight, lipid profile, and fasting glucose. A one-step dose-response meta-analysis generated effect sizes, reported as standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs).
Results: Three randomized controlled trials involving 1454 patients showed that a 42-mg daily dose of lumateperone significantly improved depressive symptoms (SMD = -0.26; 95% CI: -0.51, -0.02), Clinical Global Impression-Bipolar-Severity (CGI-BP-S) overall bipolar illness (SMD = -0.31; 95% CI: -0.45, -0.16), CGI-BP-S bipolar depression (SMD = -0.33; 95% CI: -0.48, -0.17), quality of life (SMD = 0.22; 95% CI: 0.07, 0.36), and responder rate (RR = 1.27; 95% CI: 1.05, 1.53), but not remitter rate (1.06; 95% CI: 0.81, 1.38). Compared with placebo, discontinuation due to AE significantly increased at the 42 mg dose (RR = 3.12; 95% CI: 1.68, 5.80), but not at 28 mg (1.58; 95% CI: 0.25, 9.89). Moreover, dropout rates (42 mg RR = 1.15; 95% CI: 0.76, 1.73) and other safety outcomes did not exhibit a dose-response trend.
Conclusions: Preliminary evidence suggests that 42 mg daily of lumateperone may provide clinical benefit in bipolar depression, yet the higher rate of AE-related discontinuation warrants caution in practice. However, current data remain limited, requiring further studies to establish the optimal dosing range balancing efficacy and safety.
期刊介绍:
The Journal of Psychopharmacology is a fully peer-reviewed, international journal that publishes original research and review articles on preclinical and clinical aspects of psychopharmacology. The journal provides an essential forum for researchers and practicing clinicians on the effects of drugs on animal and human behavior, and the mechanisms underlying these effects. The Journal of Psychopharmacology is truly international in scope and readership.