Fixed-Dose Brexpiprazole and Sertraline Combination Therapy for the Treatment of Posttraumatic Stress Disorder: A Phase 3, Randomized Trial.

IF 2.8 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Clinical Psychopharmacology Pub Date : 2025-09-22 DOI:10.1097/JCP.0000000000002076

Lori L Davis, Saloni Behl, Daniel Lee, Hui Zeng, Taisa Skubiak, Shelley Weaver, Nanco Hefting, Klaus Groes Larsen, Mary Hobart

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引用次数: 0

Abstract

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.

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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

目的：本试验旨在探讨固定剂量brexpiprazole联合舍曲林治疗创伤后应激障碍（PTSD）的疗效、安全性和耐受性。方法：这是一项3期、随机、平行组试验，在美国95个地点的成年PTSD门诊患者中进行（ClinicalTrials.gov: NCT04174170）。在1周的安慰剂治疗后，参与者进入11周的随机（1:1:1）双盲治疗，brexpiprazole 2mg /d+舍曲林150mg /d， brexpiprazole 3mg /d+舍曲林150mg /d，或舍曲林150mg /d+安慰剂（主动对照）。主要终点是从随机化（第1周）到第10周，临床给药PTSD量表DSM-5 （CAPS-5）总分的变化。安全性也进行了评估。结果：该试验（2019年10月至2023年8月）筛选了1821名参与者，并随机分配了553名（brexpiprazole 2mg +舍曲林，n=191； brexpiprazole 3mg +舍曲林，n=185；舍曲林+安慰剂，n=177）。各组cap -5总分均降低[第10周LS平均值（SE）变化：布雷克斯哌唑2 mg+舍曲林，-16.5 (1.2),n=132；布雷哌唑3mg +舍曲林，-18.3 (1.2),n=124；舍曲林+安慰剂，-17.6 (1.2),n=130]。第10周与舍曲林+安慰剂相比，LS平均差异（95% CI）：布雷哌唑2 mg+舍曲林，1.03(-2.09至4.16)，P=0.52；brexpiprazole 3mg +舍曲林，-0.71 (-3.88 ~ 2.46)，P=0.66。brexpiprazole+舍曲林组治疗后出现的不良事件发生率≥5%为头痛（brexpiprazole 2mg +舍曲林，7.0%；brexpiprazole 3mg +舍曲林，5.6%；舍曲林+安慰剂，7.6%）、恶心（4.9%;8.3%;8.7%）和腹泻（3.8%;6.1%;6.4%）。结论：固定剂量brexpiprazole+舍曲林与舍曲林+安慰剂对PTSD症状的改善效果相似；未达到主要终点。这与之前的两项试验不同，这两项试验显示布雷哌唑+舍曲林比舍曲林+安慰剂更有效。没有观察到新的安全信号。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Psychopharmacology 医学-精神病学

CiteScore

4.00

自引率

3.40%

发文量

231

审稿时长

4-8 weeks

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.