New York Medical College, Valhalla, New York.
Corresponding Author: Leslie Citrome, MD, MPH, New York Medical College, 40 Sunshine Cottage Rd, Valhalla, NY 10595 (
J Clin Psychiatry. 2024 Feb 28;85(1):23m15095. doi: 10.4088/JCP.23m15095.
Aripiprazole lauroxil (AL) 1064 mg every 2 months following initiation using the AL NanoCrystal Dispersion formulation (AL) plus 30-mg oral aripiprazole was efficacious and well tolerated in a 25-week, randomized, double-blind phase 3 trial in adults with acute schizophrenia. This post hoc analysis further characterized the safety of AL 1064 mg administered every 2 months and that of active control paliperidone palmitate (PP) 156 mg monthly based on occurrence, timing, and severity of adverse events (AEs) associated with antipsychotic medications. This study was conducted between November 2017 and March 2019. AL or PP was initiated during an inpatient stay of ≥ 2 weeks with transition to outpatient treatment thereafter. Rates of AEs of clinical interest, including injection site reactions (ISRs), motor AEs, sedation, hypotension, prolactin level increase, weight gain, and suicidal ideation/behavior, were summarized through weeks 4, 9, and 25 for each treatment. Of 200 patients who received ≥ 1 dose of study treatment, 99 (49.5%) completed the study (AL, 57%; PP, 43%). Mean (SD) baseline Positive and Negative Syndrome Scale total scores were 94.1 (9.04) and 94.6 (8.41) in the AL and PP treatment groups, respectively. AEs were reported by 69/99 (70%) patients administered AL and 72/101 (71%) administered PP; most AEs were mild or moderate in severity. ISRs (AL, 18.2%; PP, 26.7%) occurred primarily on days 1 and 8. All akathisia/restlessness AEs (AL, 10.1%; PP, 11.9%) occurred during the first 4 weeks; <10% of patients (either treatment) experienced hypotension, sedation, or suicidal ideation/behavior events. Weight gain of ≥ 7% from baseline occurred in 9.3% of AL- and 23.8% of PP-treated patients. Median prolactin concentrations changed by -4.60 and -3.55 ng/mL among AL-treated males and females, respectively, and did not exceed 2 times normal levels in any AL-treated patients. In PP-treated patients, changes were 21.20 and 80.40 ng/mL and concentrations exceeded 2 times normal in 38% and 88% of males and females, respectively. No new early- or late-emerging safety concerns were observed through 25 weeks of treatment with AL 1064 mg every 2 months following initiation using AL plus 30-mg oral aripiprazole. Results were consistent with known safety profiles of AL and PP and support the safety of AL 1064 mg every 2 months initiated using AL plus 30-mg oral aripiprazole. ClinicalTrials.gov identifier: NCT03345979.
阿立哌唑月桂酸酯（AL）1064mg，每 2 个月一次，在使用 AL 纳米晶体分散制剂（AL）起始治疗后[1]，联合 30mg 口服阿立哌唑，在一项 25 周、随机、双盲、3 期临床试验中，对急性精神分裂症成人患者有效且耐受良好[2]。本事后分析进一步描述了每 2 个月给予阿立哌唑月桂酸酯 1064mg 的安全性，以及活性对照棕榈酸帕利哌酮（PP）每月 156mg 的安全性，基于与抗精神病药物相关的不良事件（AE）的发生、时间和严重程度[3]。这项研究于 2017 年 11 月至 2019 年 3 月进行[4]。AL 或 PP 在住院治疗≥2 周期间开始使用，此后转为门诊治疗[5]。在每个治疗的第 4、9 和 25 周，总结了与临床相关的 AE 发生率，包括注射部位反应（ISR）、运动 AE、镇静、低血压、催乳素水平升高、体重增加和自杀意念/行为[6]。在接受≥1 剂研究治疗的 200 名患者中，99 名（49.5%）完成了研究（AL 组 57%，PP 组 43%）[7]。AL 和 PP 治疗组患者的阳性和阴性症状量表总分基线均值（标准差）分别为 94.1（9.04）和 94.6（8.41）[8]。接受 AL 治疗的 69/99 名（70%）患者和接受 PP 治疗的 72/101 名（71%）患者报告了 AE；大多数 AE 的严重程度为轻度或中度[9]。ISR（AL 组 18.2%，PP 组 26.7%）主要发生在第 1 天和第 8 天[10]。所有静坐不能/不安（AL 组 10.1%，PP 组 11.9%）均发生在第 1-4 周内；<10%的患者（任何治疗）出现低血压、镇静或自杀意念/行为事件[11]。体重增加≥7%的患者分别有 9.3%的 AL 组和 23.8%的 PP 组[12]。接受 AL 治疗的男性和女性的催乳素中位数分别降低了-4.60 和-3.55ng/ml，且在任何接受 AL 治疗的患者中，浓度均未超过正常水平的 2 倍[13]。在接受 PP 治疗的患者中，变化分别为 21.20 和 80.40ng/ml，在 38%和 88%的男性和女性中，浓度分别超过正常水平的 2 倍[14]。在使用 AL 联合 30mg 口服阿立哌唑起始治疗后，每 2 个月给予阿立哌唑月桂酸酯 1064mg，25 周治疗期间未观察到新的早期或晚期安全性问题[15]。结果与阿立哌唑月桂酸酯和棕榈酸帕利哌酮已知的安全性特征一致，支持每 2 个月给予阿立哌唑月桂酸酯 1064mg 的安全性[16]。临床试验注册号：NCT03345979[17]。
