Lori L Davis, Saloni Behl, Daniel Lee, Hui Zeng, Taisa Skubiak, Shelley Weaver, Nanco Hefting, Klaus Groes Larsen, Mary Hobart
{"title":"固定剂量布雷哌唑和舍曲林联合治疗创伤后应激障碍：一项3期随机试验","authors":"Lori L Davis, Saloni Behl, Daniel Lee, Hui Zeng, Taisa Skubiak, Shelley Weaver, Nanco Hefting, Klaus Groes Larsen, Mary Hobart","doi":"10.1097/JCP.0000000000002076","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This trial aimed to investigate the efficacy, safety, and tolerability of fixed-dose brexpiprazole in combination with sertraline for posttraumatic stress disorder (PTSD).</p><p><strong>Methods: </strong>This was a phase 3, randomized, parallel-arm trial in adult outpatients with PTSD, across 95 sites in the United States (ClinicalTrials.gov: NCT04174170). After a 1-week placebo run-in, participants entered 11 weeks of randomized (1:1:1) double-blind treatment with brexpiprazole 2 mg/d+sertraline 150 mg/d, brexpiprazole 3 mg/d+sertraline 150 mg/d, or sertraline 150 mg/d+placebo (active control). The primary endpoint was the change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score from randomization (week 1) to week 10. Safety was also assessed.</p><p><strong>Findings: </strong>The trial (October 2019 to August 2023) screened 1821 participants, and randomized 553 (brexpiprazole 2 mg+sertraline, n=191; brexpiprazole 3 mg+sertraline, n=185; and sertraline+placebo, n=177). All groups showed CAPS-5 total score reductions [LS mean (SE) change at week 10: brexpiprazole 2 mg+sertraline, -16.5 (1.2), n=132; brexpiprazole 3 mg+sertraline, -18.3 (1.2), n=124; and sertraline+placebo, -17.6 (1.2), n=130]. LS mean differences (95% CI) versus sertraline+placebo at week 10: brexpiprazole 2 mg+sertraline, 1.03 (-2.09 to 4.16), P=0.52; brexpiprazole 3 mg+sertraline, -0.71 (-3.88 to 2.46), P=0.66. Treatment-emergent adverse events with incidence ≥5% for either brexpiprazole+sertraline group were headache (brexpiprazole 2 mg+sertraline, 7.0%; brexpiprazole 3 mg+sertraline, 5.6%; and sertraline+placebo, 7.6%), nausea (4.9%; 8.3%; 8.7%), and diarrhea (3.8%; 6.1%; 6.4%).</p><p><strong>Conclusions: </strong>PTSD symptom improvement was similar with fixed-dose brexpiprazole+sertraline and sertraline+placebo; the primary endpoint was not met. This differs from 2 prior trials that showed greater efficacy for brexpiprazole+sertraline versus sertraline+placebo. No new safety signals were observed.</p>","PeriodicalId":15455,"journal":{"name":"Journal of Clinical Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Fixed-Dose Brexpiprazole and Sertraline Combination Therapy for the Treatment of Posttraumatic Stress Disorder: A Phase 3, Randomized Trial.\",\"authors\":\"Lori L Davis, Saloni Behl, Daniel Lee, Hui Zeng, Taisa Skubiak, Shelley Weaver, Nanco Hefting, Klaus Groes Larsen, Mary Hobart\",\"doi\":\"10.1097/JCP.0000000000002076\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>This trial aimed to investigate the efficacy, safety, and tolerability of fixed-dose brexpiprazole in combination with sertraline for posttraumatic stress disorder (PTSD).</p><p><strong>Methods: </strong>This was a phase 3, randomized, parallel-arm trial in adult outpatients with PTSD, across 95 sites in the United States (ClinicalTrials.gov: NCT04174170). After a 1-week placebo run-in, participants entered 11 weeks of randomized (1:1:1) double-blind treatment with brexpiprazole 2 mg/d+sertraline 150 mg/d, brexpiprazole 3 mg/d+sertraline 150 mg/d, or sertraline 150 mg/d+placebo (active control). The primary endpoint was the change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score from randomization (week 1) to week 10. Safety was also assessed.</p><p><strong>Findings: </strong>The trial (October 2019 to August 2023) screened 1821 participants, and randomized 553 (brexpiprazole 2 mg+sertraline, n=191; brexpiprazole 3 mg+sertraline, n=185; and sertraline+placebo, n=177). All groups showed CAPS-5 total score reductions [LS mean (SE) change at week 10: brexpiprazole 2 mg+sertraline, -16.5 (1.2), n=132; brexpiprazole 3 mg+sertraline, -18.3 (1.2), n=124; and sertraline+placebo, -17.6 (1.2), n=130]. LS mean differences (95% CI) versus sertraline+placebo at week 10: brexpiprazole 2 mg+sertraline, 1.03 (-2.09 to 4.16), P=0.52; brexpiprazole 3 mg+sertraline, -0.71 (-3.88 to 2.46), P=0.66. Treatment-emergent adverse events with incidence ≥5% for either brexpiprazole+sertraline group were headache (brexpiprazole 2 mg+sertraline, 7.0%; brexpiprazole 3 mg+sertraline, 5.6%; and sertraline+placebo, 7.6%), nausea (4.9%; 8.3%; 8.7%), and diarrhea (3.8%; 6.1%; 6.4%).</p><p><strong>Conclusions: </strong>PTSD symptom improvement was similar with fixed-dose brexpiprazole+sertraline and sertraline+placebo; the primary endpoint was not met. This differs from 2 prior trials that showed greater efficacy for brexpiprazole+sertraline versus sertraline+placebo. No new safety signals were observed.</p>\",\"PeriodicalId\":15455,\"journal\":{\"name\":\"Journal of Clinical Psychopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Psychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/JCP.0000000000002076\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/JCP.0000000000002076","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Fixed-Dose Brexpiprazole and Sertraline Combination Therapy for the Treatment of Posttraumatic Stress Disorder: A Phase 3, Randomized Trial.
Purpose: This trial aimed to investigate the efficacy, safety, and tolerability of fixed-dose brexpiprazole in combination with sertraline for posttraumatic stress disorder (PTSD).
Methods: This was a phase 3, randomized, parallel-arm trial in adult outpatients with PTSD, across 95 sites in the United States (ClinicalTrials.gov: NCT04174170). After a 1-week placebo run-in, participants entered 11 weeks of randomized (1:1:1) double-blind treatment with brexpiprazole 2 mg/d+sertraline 150 mg/d, brexpiprazole 3 mg/d+sertraline 150 mg/d, or sertraline 150 mg/d+placebo (active control). The primary endpoint was the change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score from randomization (week 1) to week 10. Safety was also assessed.
Findings: The trial (October 2019 to August 2023) screened 1821 participants, and randomized 553 (brexpiprazole 2 mg+sertraline, n=191; brexpiprazole 3 mg+sertraline, n=185; and sertraline+placebo, n=177). All groups showed CAPS-5 total score reductions [LS mean (SE) change at week 10: brexpiprazole 2 mg+sertraline, -16.5 (1.2), n=132; brexpiprazole 3 mg+sertraline, -18.3 (1.2), n=124; and sertraline+placebo, -17.6 (1.2), n=130]. LS mean differences (95% CI) versus sertraline+placebo at week 10: brexpiprazole 2 mg+sertraline, 1.03 (-2.09 to 4.16), P=0.52; brexpiprazole 3 mg+sertraline, -0.71 (-3.88 to 2.46), P=0.66. Treatment-emergent adverse events with incidence ≥5% for either brexpiprazole+sertraline group were headache (brexpiprazole 2 mg+sertraline, 7.0%; brexpiprazole 3 mg+sertraline, 5.6%; and sertraline+placebo, 7.6%), nausea (4.9%; 8.3%; 8.7%), and diarrhea (3.8%; 6.1%; 6.4%).
Conclusions: PTSD symptom improvement was similar with fixed-dose brexpiprazole+sertraline and sertraline+placebo; the primary endpoint was not met. This differs from 2 prior trials that showed greater efficacy for brexpiprazole+sertraline versus sertraline+placebo. No new safety signals were observed.
期刊介绍：
Journal of Clinical Psychopharmacology, a leading publication in psychopharmacology, offers a wide range of articles reporting on clinical trials and studies, side effects, drug interactions, overdose management, pharmacogenetics, pharmacokinetics, and psychiatric effects of non-psychiatric drugs. The journal keeps clinician-scientists and trainees up-to-date on the latest clinical developments in psychopharmacologic agents, presenting the extensive coverage needed to keep up with every development in this fast-growing field.
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