Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Novo Nordisk A/S, Søborg, Denmark.
JAMA Intern Med. 2024 Nov 1;184(11):1290-1300. doi: 10.1001/jamainternmed.2024.4346.
Obesity is associated with numerous psychosocial complications, making psychiatric safety a consideration for treating people with obesity. Few studies have investigated the psychiatric safety of newly available antiobesity medications.
To evaluate the psychiatric safety of subcutaneous semaglutide, 2.4 mg, once weekly in people without known major psychopathology.
DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of pooled data from the randomized, double-blind, placebo-controlled, multicenter phase 3a STEP 1, 2, and 3 trials (68 weeks; 2018-2020) and phase 3b STEP 5 trial (104 weeks; 2018-2021) included adults with overweight or obesity; STEP 2 participants also had type 2 diabetes. Trial designs have been published previously.
Semaglutide, 2.4 mg, vs placebo.
Depressive symptoms and suicidal ideation/behavior were assessed using the Patient Health Questionnaire (PHQ-9) and Columbia-Suicide Severity Rating Scale, respectively. Psychiatric and nervous system disorder adverse events were investigated.
This analysis included 3377 participants in the STEP 1, 2, and 3 trials (2360 women [69.6%]; mean [SD] age, 49 [13] years) and 304 participants in STEP 5 (236 women [77.6%]; mean [SD] age, 47 [11] years). In the STEP 1, 2, and 3 trials, mean (SD) baseline PHQ-9 scores for the semaglutide, 2.4 mg, and placebo groups were 2.0 (2.3) and 1.8 (2.3), respectively, indicating no/minimal symptoms of depression. PHQ-9 scores at week 68 were 2.0 (2.9) and 2.4 (3.3), respectively; the estimated treatment difference (95% CI) between groups was -0.56 (-0.81 to -0.32) (P < .001). Participants treated with semaglutide vs placebo were less likely to shift (from baseline to week 68) to a more severe category of PHQ-9 depression (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001). Based on the Columbia-Suicide Severity Rating Scale, 1% or fewer of participants reported suicidal ideation/behavior during treatment, with no differences between semaglutide, 2.4 mg, and placebo. Psychiatric disorder adverse events were generally balanced between groups. Similar results were observed in STEP 5.
The results of this post hoc analysis suggest that treatment with semaglutide, 2.4 mg, did not increase the risk of developing symptoms of depression or suicidal ideation/behavior vs placebo and was associated with a small but statistically significant reduction in depressive symptoms (not considered clinically meaningful). People with obesity should be monitored for mental health concerns so they can receive appropriate support and care.
ClinicalTrials.gov Identifiers: STEP 1 (NCT03548935), 2 (NCT03552757), 3 (NCT03611582), and 5 (NCT03693430).
肥胖与众多心理社会并发症相关，这使得精神医学安全性成为治疗肥胖患者的一个考虑因素。很少有研究调查新的抗肥胖药物的精神医学安全性。
评估每周皮下注射 2.4mg 司美格鲁肽在无明显主要精神病理学的人群中的精神医学安全性。
设计、地点和参与者：这是一项对随机、双盲、安慰剂对照、多中心 3a 期 STEP 1、2 和 3 试验（68 周；2018-2020 年）和 3b 期 STEP 5 试验（104 周；2018-2021 年）的汇总数据进行的事后分析，纳入了超重或肥胖的成年人；STEP 2 参与者还患有 2 型糖尿病。试验设计先前已发表。
司美格鲁肽，2.4mg，与安慰剂相比。
使用患者健康问卷（PHQ-9）和哥伦比亚自杀严重程度评定量表分别评估抑郁症状和自杀意念/行为。调查了精神和神经系统疾病不良事件。
该分析包括 3377 名 STEP 1、2 和 3 试验（2360 名女性[69.6%]；平均[标准差]年龄，49[13]岁）和 304 名 STEP 5 试验参与者（236 名女性[77.6%]；平均[标准差]年龄，47[11]岁）。在 STEP 1、2 和 3 试验中，司美格鲁肽 2.4mg 和安慰剂组的基线 PHQ-9 评分分别为 2.0（2.3）和 1.8（2.3），表明抑郁症状无/轻微。第 68 周的 PHQ-9 评分分别为 2.0（2.9）和 2.4（3.3）；组间的估计治疗差异（95%CI）为-0.56（-0.81 至-0.32）（P < .001）。与安慰剂相比，接受司美格鲁肽治疗的患者更不可能（从基线到第 68 周）向 PHQ-9 抑郁更严重的类别转移（优势比，0.63；95%CI，0.50-0.79；P < .001）。基于哥伦比亚自杀严重程度评定量表，有 1%或更少的参与者报告在治疗期间有自杀意念/行为，司美格鲁肽 2.4mg 和安慰剂组之间没有差异。精神疾病不良事件在各组之间通常平衡。STEP 5 中也观察到了类似的结果。
这项事后分析的结果表明，与安慰剂相比，司美格鲁肽 2.4mg 治疗并未增加出现抑郁症状或自杀意念/行为的风险，并且与抑郁症状的微小但具有统计学意义的减少相关（不认为具有临床意义）。肥胖患者应监测心理健康问题，以便他们能够获得适当的支持和护理。
ClinicalTrials.gov 标识符：STEP 1（NCT03548935）、2（NCT03552757）、3（NCT03611582）和 5（NCT03693430）。
