Ballon Jacob S, Kahn René S, Arevalo Christina, Dunbar Martin, McDonnell David, Correll Christoph U
Department of Psychiatry, Stanford University, Stanford, California.
Department of Psychiatry and Behavioral Health System, Icahn School of Medicine at Mount Sinai, New York, New York.
J Clin Psychiatry. 2024 Dec 4;86(1):24m15511. doi: 10.4088/JCP.24m15511.
Evaluate long-term safety, tolerability, and durability of the effect of olanzapine/samidorphan (OLZ/SAM) for up to 4 years in patients with schizophrenia, schizophreniform disorder, or bipolar I disorder (BD-I). This phase 3, multicenter, open-label, long-term extension (conducted June 2017-September 2023) assessed OLZ/SAM in patients completing the ENLIGHTEN clinical program. Patients received ≥2-4 years of additional treatment. Safety assessments included adverse event (AE) incidences and changes from baseline in body weight, waist circumference, and lipid/glycemic parameters. The durability of the effect was assessed using the Clinical Global Impressions-Severity (CGI-S) scale. Of 524 patients enrolled, 523 received ≥1 dose of OLZ/SAM. Of these, 460 (88%) patients had schizophrenia, 15 (3%) had schizophreniform disorder, and 48 (9%) had BD-I. Mean (SD) age was 35.1 (12.2) years. Mean (SD) OLZ/SAM exposure was 652.4 (454.8) days. Of 451 patients eligible for 2 years of treatment, 242 (53.7%) received it; of 335 patients eligible for 4 years, 109 (32.5%) received it. The most common AEs were weight increased (9.8%), headache (7.1%), anxiety (6.1%), insomnia (5.9%), somnolence (5.9%), nausea (5.7%), and weight decreased (5.7%). At 2 years, mean (SD) body weight change was 0.84 (6.84) kg; waist circumference change was -0.56 (6.24) cm. At 4 years, mean (SD) body weight change was 2.65 (8.12) kg; waist circumference change was 1.37 (8.65) cm. Changes in lipid/glycemic parameters were minimal. CGI-S scores remained stable. OLZ/SAM maintained symptom control with a long-term safety profile over 4 years consistent with that of prior studies. ClinicalTrials.gov identifier: NCT03201757.
评估奥氮平/沙美阿片（OLZ/SAM）对精神分裂症、分裂样精神障碍或双相I型障碍（BD-I）患者长达4年的长期安全性、耐受性及疗效持久性。这项3期、多中心、开放标签的长期扩展研究（于2017年6月至2023年9月开展）对完成ENLIGHTEN临床项目的患者中的OLZ/SAM进行了评估。患者接受了≥2至4年的额外治疗。安全性评估包括不良事件（AE）发生率以及体重、腰围和脂质/血糖参数相对于基线的变化。使用临床总体印象-严重程度（CGI-S）量表评估疗效的持久性。在入组的524例患者中，523例接受了≥1剂OLZ/SAM。其中，460例（88%）患者患有精神分裂症，15例（3%）患有分裂样精神障碍，48例（9%）患有BD-I。平均（标准差）年龄为35.1（12.2）岁。OLZ/SAM的平均（标准差）暴露时间为652.4（454.8）天。在451例符合2年治疗条件的患者中，242例（53.7%）接受了治疗；在335例符合4年治疗条件的患者中，109例（32.5%）接受了治疗。最常见的不良事件为体重增加（9.8%）、头痛（7.1%）、焦虑（6.1%）、失眠（5.9%）、嗜睡（5.9%）、恶心（5.7%）和体重减轻（5.7%）。在2年时，平均（标准差）体重变化为0.84（6.84）kg；腰围变化为-0.56（6.24）cm。在4年时，平均（标准差）体重变化为2.65（8.12）kg；腰围变化为1.37（8.65）cm。脂质/血糖参数变化极小。CGI-S评分保持稳定。OLZ/SAM在4年期间维持了症状控制，其长期安全性与先前研究一致。ClinicalTrials.gov标识符：NCT03201757。
