ImportanceCurrently there is no standard therapy to improve cancer-related anorexia, hampering survival. Mirtazapine has been suggested as a feasible option in this context.ObjectivesTo assess the effect of mirtazapine on appetite and energy consumption in patients with advanced non–small cell lung cancer (NSCLC).Design, Setting, and ParticipantsThis randomized, double-blind, placebo-controlled clinical trial including adults was performed in a tertiary cancer care center from August 2018 to May 2022 with a follow-up of 8 weeks. Overall, 134 patients were screened; 114 were assessed for eligibility and 28 were excluded.InterventionsPatients were randomized in a 1:1 ratio to receive mirtazapine, 15 mg, or placebo for 2 weeks followed by a dose escalation to 30 mg until week 8 or placebo. Both groups received nutritional assessment and dietary advice.Main outcomes and measuresAppetite was assessed by the Anorexia Cachexia Scale and energy intake. Dietary parameters were evaluated at baseline, 4 weeks, and 8 weeks, with a 24-hour dietary recall, and energy quantification based on the Mexican system of nutritional equivalents.ResultsA total of 86 patients met the inclusion criteria and were randomized to the placebo (n = 43) or the mirtazapine group (n = 43). The mean (SD) age was 63.5 (11.2) years, 41 were women (57.7%) and had adenocarcinoma, Eastern Cooperative Oncology Group performance status scale score of 1, stage IV NSCLC, and were receiving first-line treatment. Baseline characteristics were similar between groups. There was no difference in appetite scores in patients who received mirtazapine or placebo after 4 and 8 weeks. After 4 weeks, mirtazapine significantly increased energy intake (379.3 kcal; 95% CI, 1382.6-576.1; P < .001) including proteins (22.5 g; 95% CI, 11.5-33.4; P = .001), carbohydrates (43.4 g; 95% CI, 13.1-73.8; P = .006), and fats (13.2 g; 95% CI, 6.0-20.4; P = .006). Fats intake was significantly higher in patients in the mirtazapine group (14.5 g vs 0.7 g; P = .02) after 8 weeks. The mirtazapine group significantly decreased the proportion of patients with sarcopenia (82.8% vs 57.1%, P = .03) at 8 weeks. Patients on mirtazapine tolerated the treatment well, but reported a higher perception of nightmares at 2 weeks based on a 10 cm VAS score (0 [25th-75th percentile, 0-1] vs 0 [25th-75th percentile, 0-0] in the control group; P = .009) but this finding was nonsignificant after 4 and 8 weeks.Conclusion and RelevanceIn this randomized clinical trial of patients with advanced NSCLC, there was no difference in appetite scores in all patients who received mirtazapine or placebo, but the mirtazapine group had a significant increase in energy intake through the 4- and 8-week follow-up, mainly in fat intake, which is a better and crucial source of energy. The addition of mirtazapine in the treatment of patients with advanced NSCLC and anorexia may help these patients achieve their energy requirements and improve health-related quality of life, specifically emotional and cognitive functioning.Trial RegistrationClinicalTrials.gov Identifier: NCT04748523

中文翻译：

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米氮平作为非小细胞肺癌和厌食症患者的食欲兴奋剂

重要性目前还没有标准疗法可以改善癌症相关的厌食症，从而影响生存。在这种情况下，米氮平被认为是一种可行的选择。目的评估米氮平对晚期非小细胞肺癌 (NSCLC) 患者食欲和能量消耗的影响。设计、设置和参与者这项随机、双盲、安慰剂研究2018年8月至2022年5月在三级癌症护理中心进行了包括成人在内的对照临床试验，随访8周。总共筛查了 134 名患者；114 人接受了资格评估，28 人被排除。 干预措施 患者以 1:1 的比例随机接受米氮平 15 mg 或安慰剂治疗 2 周，然后剂量递增至 30 mg 直至第 8 周或接受安慰剂治疗。两组均接受营养评估和饮食建议。 主要结果和措施通过厌食恶病质量表和能量摄入来评估食欲。在基线、4周和8周时评估饮食参数，并进行24小时饮食回忆，并根据墨西哥营养当量系统进行能量量化。结果共有86名患者符合纳入标准，并被随机分配至安慰剂组（ n = 43) 或米氮平组 (n = 43)。平均 (SD) 年龄为 63.5 (11.2) 岁，41 名女性 (57.7%) 患有腺癌，东部肿瘤合作组表现状态量表评分为 1，IV 期 NSCLC，正在接受一线治疗。各组之间的基线特征相似。4 周和 8 周后接受米氮平或安慰剂治疗的患者食欲评分没有差异。4周后，米氮平显着增加能量摄入（379.3 kcal；95% CI，1382.6-576.1；磷< .001) 包括蛋白质 (22.5 g; 95% CI, 11.5-33.4;磷= .001），碳水化合物（43.4 克；95% CI，13.1-73.8；磷= .006) 和脂肪 (13.2 g; 95% CI, 6.0-20.4;磷=.006）。米氮平组患者的脂肪摄入量显着较高（14.5 克 vs 0.7 克；磷= .02) 8 周后。米氮平组显着降低了肌少症患者的比例（82.8% vs 57.1%，磷= .03) 8 周时。接受米氮平治疗的患者对治疗的耐受性良好，但根据 10 cm VAS 评分（0 [25-75%，0-1] 与 0 [25-75%，0-0]对照组；磷= .009），但这一发现在 4 周和 8 周后不显着。结论和相关性在这项针对晚期 NSCLC 患者的随机临床试验中，所有接受米氮平或安慰剂治疗的患者的食欲评分没有差异，但米氮平组的食欲评分没有差异通过4周和8周的随访，能量摄入量显着增加，主要是脂肪摄入量，这是更好、更重要的能量来源。在晚期 NSCLC 和厌食症患者的治疗中添加米氮平可能有助于这些患者满足能量需求并改善与健康相关的生活质量，特别是情绪和认知功能。 试验注册ClinicalTrials.gov 标识符：NCT04748523