Advancements in the Clinical Use of Antidepressants for Adolescent Depression
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摘要: 青少年抑郁症患者相较于成年抑郁症患者，具有更高的发病率、较差的生活质量和治疗效果。国际指南普遍推荐轻度青少年抑郁症优先考虑心理治疗，对于中重度患者，抗抑郁药物联合心理治疗是1种可行的选择，如何选择适合的抗抑郁药物仍然是待解决的难题。抗抑郁药物存在一系列副作用，包括睡眠障碍、锥体外系反应和消化道反应等，为了减轻这些副作用并提高临床疗效，个体化的治疗方案至关重要。总结了青少年抑郁症的发病机制、抗抑郁药物的药代动力学和副作用，以及2013～2023年针对青少年抑郁症患者的用药指南，并针对青少年抑郁症患者药物治疗方案提出科学建议。Abstract: Compared with adult patients with depression, adolescents with depression have a higher incidence rate, poorer quality of life and poorer treatment effects. International guidelines generally recommend giving priority to psychological treatment for mild adolescent depression. For moderate to severe patients, antidepressant drugs combined with psychotherapy are a feasible option. How to choose suitable antidepressant drugs is still a problem to be solved. Antidepressant drugs have a series of side effects, including sleep disorders, extrapyramidal reactions, and gastrointestinal reactions. In order to reduce these side effects and improve clinical efficacy, individualized treatment plans are crucial. This article summarizes the pathogenesis of adolescent depression, the pharmacokinetics and side effects of antidepressant drugs, as well as the medication guidelines for adolescent patients with depression from 2013 to 2023, and provides scientific suggestions for drug treatment options for adolescent patients with depression.
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Key words:
- Adolescent /
- Depression /
- Antidepressive agents /
- Pharmacokinetics /
- Efficacy /
- Side effects
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表 1 各类青少年抑郁症患者抗抑郁药物治疗相关指南
Table 1. Guidelines for antidepressant medication treatment in adolescents with various types of depression
机构 年份 SSRIs SNRIs 建议 参考文献 用药依据 指南依据的文献 CSBM 2022 SSRIs类（首选） — 遵循抗抑郁药与心理治疗并重的原则 [33] SSRIs类疗效及安全
性有循证医学证据支持[34] APA 2021 氟西汀 — 建议联合心理治疗 [30] 伦理原则和行为准则 [35] RANZCP 2021 氟西汀 — 心理治疗为一线治疗 [32] 有抗抑郁药物（氟西汀）对青少年患者有效的一级证据 [36] KSAD、KCNP 2021 艾司西酞普兰（首选）、氟西汀、舍曲林 — 用于轻中度抑郁发作的青少年 [25] 氟西汀和舍曲林疗效显著 [37] JSCNP（未特别提及青少年抑郁症） 2020 艾司西酞普兰、舍曲林 度洛西汀、文拉法辛 若SSRIs无效，一线治疗切换为SNRIs/或米氮平;而若SNRIs无效，推荐改用米氮平，反之亦然（若米氮平无效，改用SNRIs）。 [26] 对于轻度抑郁症，SSRIs被选为一线治疗，SNRIs被选为二线治疗，对于米氮平没有达成共识 [28，38−39] AFPBN
（未特别提及
青少年抑郁症）2019 SSRIs类 SNRIs 无论临床严重程度如何，SSRIs及SNRIs均被认为是一线治疗药物 [27] 三环类抗抑郁药、米氮平或米安色林可增强SRRIs
疗效[40−41] NICE 2019 氟西汀 — 轻度抑郁症不应使用抗抑郁药物，中重度抑郁症，如果在4～6个疗程的心理治疗无效后，可以给予氟西汀治疗 [31] 如表现出严重自我伤害，应遵循良好的自我伤害指导立即处理 — CANMAT 2016 SSRIs类 — SSRIs会增加青少年自杀风险，建议谨慎使用并密切监测 [28] 氟西汀、文拉法辛与安慰剂相比自杀风险无差别；帕罗西汀的风险较安慰剂低。 [42−43] GLAD-PC 2015 氟西汀（FDA批准）、艾司西酞普兰（FDA批准）、西酞普兰、氟伏沙明、帕罗西汀、舍曲林 — 除氟西汀外，所有SSRIs在停用时都应缓慢减量，因为存在停药的风险 [22] 根据青少年患者的临床表现、医生的处方偏好 [44] WFSBP 2015 氟西汀、舍曲林 文拉法辛 — [24] 有效缓解儿童和青少年抑郁症状，具有预防新抑郁发作的潜力。 [45−47] SSRIs:选择性5-羟色胺再摄取抑制剂；SNRIs:选择性5-羟色胺和去甲肾上腺素再摄取抑制剂；FDA：美国食品药品管理局；CSBM：中华医学会行为医学分会；APA：美国心理学协会；RANZCP：澳大利亚与新西兰皇家精神科医师学会；KSAD：韩国情感障碍学会；KCNP：韩国神经精神药理学学院；JSCNP：日本临床神经精神药理学学会；AFPBN：法国生物精神病学和神经精神药理学协会；NICE：英国国家卫生与临床优化研究所；CANMAT：加拿大情绪和焦虑治疗网络；GLAD-PC：美国青少年抑郁症初级护理指南；WFSBP：世界生物精神病学学会联合会。 
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表 2 FDA批准可用于青少年患者的抗抑郁药物汇总
Table 2. Summary of FDA-approved antidepressant medications for adolescent patients
药物名称 达峰
时间/h[48]半衰期[48] 主要
代谢酶[49]年龄范围
/岁[50]适应症[23] 目标剂量[50] 药物的相对受体结合亲和力[51] SET DAT NET α1 M1 H1 氟西汀（SSRI） 6～8 2～3 d CYP2C9 、CYP2C19、CYP2D6 8～17 抑郁症、
强迫症40 mg/d 1 >1000 545 >1000 638 >1000 艾司西酞普兰（SSRI） 4 27～33 h CYP3A4、CYP2C19、CYP2D6 12～17 抑郁症 >10 mg/d 1 >10000 >1000 >1000 >1000 257 舍曲林（SSRI） 6～8 26 h
CYP2C19、
CYP3A46～17 强迫症 150 mg/d 1 220 >1000 >1000 >1000 >100000 氟伏沙明（SSRI） 5 22 h CYP2D6 8～17 强迫症 40 mg/d 1 >1000 620 560 >5000 >5000 度洛西汀（SNRI） 6 8～17 h CYP1A2 7～17 广泛性
焦虑障碍60～90 mg/d 1 504 7.5 >1000 >1000 >1000 FDA：美国食品药品管理局；SSRI:选择性5-羟色胺再摄取抑制剂；SNRI：选择性5-羟色胺和去甲肾上腺素再摄取抑制剂；SET：5-羟色胺转运体；DAT：多巴胺转运体；NET：去甲肾上腺素转运体；M：毒蕈碱受体；H：组胺受体；α1：α1-肾上腺素受体。相对受体结合亲和力是指药物与每个受体相对于药物最高亲和力部位的结合亲和力，数值越大，与药物下一个潜在靶点结合所需的浓度就越高。
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