Icahn School of Medicine at Mount Sinai, New York, New York.
Zucker Hillside Hospital, Glen Oaks, New York.
J Clin Psychiatry. 2023 Mar 22;84(3):22m14674. doi: 10.4088/JCP.22m14674.
Patients with early-phase schizophrenia or bipolar I disorder (BD-I) are at greater risk for antipsychotic-associated weight gain. This 12-week, randomized, double-blind study conducted between June 2017 and December 2021 evaluated weight effects of combination olanzapine and samidorphan (OLZ/SAM) versus olanzapine in early-phase illness. Young adults (16-39 years) with schizophrenia, schizophreniform disorder, or BD-I, < 4 years since symptom onset, body mass index < 30 kg/m, and < 24 weeks' cumulative antipsychotic exposure were randomized to OLZ/SAM (5-20/10 mg/d) or olanzapine (5-20 mg/d). Primary endpoint was percent change from baseline body weight at week 12. Secondary endpoints, tested hierarchically, were proportions of patients with ≥ 10% or ≥ 7% weight gain, waist circumference change, and Clinical Global Impressions-Severity (CGI-S) change. Of 428 patients (OLZ/SAM, n = 213; olanzapine, n = 215), 408 had ≥ 1 postbaseline weight assessment and were analyzed. Percent weight change was significantly lower with OLZ/SAM versus olanzapine (4.91% vs 6.77%; least-squares mean [LSM] [SE] difference, -1.87% [0.75]; = .012). Although fewer patients treated with OLZ/SAM had ≥ 10% weight gain, the difference was not statistically significant versus olanzapine (21.9% vs 30.4%, respectively; OR = 0.64; 95% CI 0.39 to 1.05); hierarchical testing precluded further statistical evaluation of secondary endpoints. Proportions of patients with ≥ 7% weight gain (33.1% vs 44.8%; OR = 0.61, 95% CI = 0.39 to 0.94) and waist circumference change (2.99 vs 3.90 cm; LSM [SE] difference, -0.92 cm [0.58]; 95% CI = -2.06 to 0.22) favored OLZ/SAM. LSM (SE) CGI-S change with OLZ/SAM was -0.82 (0.06). OLZ/SAM and olanzapine had similar safety profiles, including small, similar metabolic parameter changes. In patients with early-phase schizophrenia, schizophreniform disorder, or BD-I, OLZ/SAM treatment resulted in less weight gain versus olanzapine. ClinicalTrials.gov identifier: NCT03187769.
患有早期精神分裂症或双相情感障碍 I 型（BD-I）的患者发生抗精神病药相关体重增加的风险更高。这项于 2017 年 6 月至 2021 年 12 月进行的为期 12 周、随机、双盲研究评估了奥氮平与萨米多弗（OLZ/SAM）联合用药与奥氮平在早期疾病阶段的体重影响。年轻患者（16-39 岁）患有精神分裂症、分裂情感障碍或 BD-I，发病时间<4 年，体重指数（BMI）<30kg/m2，累积抗精神病药暴露时间<24 周，被随机分配至 OLZ/SAM（5-20/10mg/d）或奥氮平（5-20mg/d）组。主要终点为第 12 周时体重相对于基线的百分比变化。次要终点按层次顺序进行检验，包括体重增加≥10%或≥7%的患者比例、腰围变化和临床总体印象严重程度（CGI-S）变化。428 例患者（OLZ/SAM，n=213；奥氮平，n=215）中，有 408 例患者至少有 1 次基线后体重评估，并进行了分析。与奥氮平相比，OLZ/SAM 治疗患者的体重变化百分比明显更低（4.91% vs 6.77%；最小二乘均值 [LSM] [SE]差异，-1.87% [0.75]；=0.012）。尽管接受 OLZ/SAM 治疗的患者中体重增加≥10%的比例较少，但与奥氮平相比差异无统计学意义（分别为 21.9% vs 30.4%；比值比 [OR] =0.64；95%CI：0.39 至 1.05）；分层检验排除了对次要终点的进一步统计学评估。体重增加≥7%的患者比例（33.1% vs 44.8%；OR=0.61，95%CI：0.39 至 0.94）和腰围变化（2.99cm vs 3.90cm；LSM [SE]差异，-0.92cm [0.58]；95%CI：-2.06 至 0.22）有利于 OLZ/SAM。OLZ/SAM 的 LSM（SE）CGI-S 变化为-0.82（0.06）。OLZ/SAM 和奥氮平具有相似的安全性特征，包括较小的、相似的代谢参数变化。在患有早期精神分裂症、分裂情感障碍或 BD-I 的患者中，与奥氮平相比，OLZ/SAM 治疗导致体重增加较少。临床试验注册编号：NCT03187769。
