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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在牙列拥挤的人类学调查中，中国人和日本人严重拥挤患病率较高[1]。牙列拥挤易发生在前牙区[2]，且随年龄增加，拥挤加剧[3-4]。上颌唇向低位尖牙在前牙拥挤病例中高发，这与牙弓长度、宽度发育不足密切相关[5- 6]。Akram[7]在上颌唇向低位尖牙的CBCT研究中发现，上颌唇向低位尖牙因不能行使正常咬合功能，牙根较短，骨体积、颊侧骨密度比正常尖牙组减少。这不仅影响患者美观，也造成牙周组织的损伤，需进行正畸治疗。但唇向低位尖牙因其牙周退行性变，正畸治疗过程中受力更易发生牙龈退缩、牙槽骨吸收[8-9]。
牙齿受到各种内在、外在、动态、静态的机械力，这些力共同驱动和维持生理性牙槽骨生长发育和平衡。有动物研究表明，恢复咬合功能低下牙的咬合刺激可诱导骨附着、增加牙槽骨表面骨量。课题组提出设想在正畸之前给予患者力学干预，恢复其牙周组织活性再对其进行矫治，以减少牙槽骨丧失风险。如何给予适当的力干预？传统固定矫治技术中，弓丝形状、力学行为、牙齿运动情况间的关系并不十分明确。临床医师无法准确预测应施加矫治力值的大小。近年来，无托槽压膜式矫治器以其可精准施力，精确设计的优点，越来越被医生和患者接纳。为解决这一难题，课题组使用数字化技术设计矫治器施力干预上颌唇向低位尖牙后再行常规矫治，探索此干预措施能否降低牙槽骨吸收量，提高正畸安全性。
1. 资料与方法
1.1 研究对象及分组
1.1.1 研究对象
筛选自2021年10月至2023年8月到云南大学附属医院口腔正畸科就诊有上颌唇向低位尖牙的成年患者，且均在云南大学附属医院口腔临床中心拍摄CBCT，所有患者签署知情同意书，该研究通过医院伦理委员会审查（批准号：2021063）。纳入标准：（1）年龄≥18岁，恒牙列，牙根发育完成，根尖无暗影，牙冠形态完整规则；（2）牙周健康或牙周病控制良好；（3）上颌尖牙唇向低位（距离咬合平面2 mm以上）患者。排除标准：（1）无正畸、正颌治疗史、前牙牙体或修复治疗史；（2）无唇腭裂或全身系统性、怀孕、遗传性疾病史；（3）上颌尖牙无明显扭转，无外伤、囊肿或手术史。
1.1.2 研究对象分组
课题组选择用数字化设计干预矫治器，给予无咬合力接触的尖牙沿长轴方向压低0.1 mm，每日佩戴4 h，连续佩戴3个月后开始常规的固定或隐形矫治。与患者沟通交流，将愿意进行干预的患者纳入干预组，否则进入对照组。
1.2 研究方法
1.2.1 釉牙骨质界到牙槽嵴顶的距离（CEJ-AC）
纳入的患者，在治疗前及低位尖牙纳入牙弓后均进行CBCT检测（NNTviewer，New Tom，Italy），扫描视野15 cm×15 cm，电压110 KVp，电流3.83 Ma，曝光时间3.6 s，扫描层厚0.3 mm。
选取尖牙最大矢状截面为牙槽嵴顶与CEJ距离的测量平面（图1）。步骤如下：如图A在轴面上，使横轴与竖轴垂直且交点位于牙体中心；在B、C调节冠状面、矢状面上牙体长轴与竖轴的重叠，此时为牙根横截面积最大面，以矢状面 C为测量界面。
图 1 确定上颌尖牙牙体长轴A：水平面；B：冠状面；C：矢状面。Figure 1. Confirmation of long axis of upper cannine测量并记录纳入病例治疗前后唇向低位尖牙唇侧牙槽嵴顶与釉牙骨质界距离h1（图2）。同一测量者在1个月后重复测量，取2次测量结果的平均值。
图 2 确定釉牙骨质界到牙槽嵴顶（CEJ-AC）的距离h1Figure 2. Confirmation of the distance of cemento-enamel bone junction （CEJ）-alveolar bone crest（AC） h11.2.2 牙龈生物型的临床检测
采用Kan[10]提出的牙周探针检测牙龈生物型的方法，即将William牙周探针插入龈沟内，观察牙周探针若能透过牙龈被看到则为薄龈型，否则为厚龈型。
1.3 统计学处理
对纳入的患者进行治疗前后CBCT测量，并对临床检测指标进行统计分析。采用 SPSS22.0软件对数据进行处理。计量资料以均数±标准差（
$ \bar{x} \pm s $ ）表示，前后差异比较采用配对t检验，两组差异比较采用成组t检验；计数资料用n（%）表示。以P < 0.05为差异有统计学意义。2. 结果
2.1 一般情况
收集病例43例（牙数54颗），其中男性15例（牙数21颗），女性28例（牙数33颗），患者年龄18～40岁。分为常规矫治组和干预矫治组，常规矫治组26例（牙数32颗），其中男性8例（牙数11颗），女性18例（牙数21颗），患者年龄18～33岁；干预矫治组17例（牙数22颗），其中男性7例（牙数10颗），女性10例（牙数12颗），患者年龄18～40岁。
2.2 干预措施对釉牙骨质界到牙槽嵴顶的距离（CEJ-AC）的影响
矫治前2组无统计学差异，矫治后干预组CEJ-AC降低（P < 0.05），常规矫治组CEJ-AC不变，且干预矫治组干预前后CEJ-AC差值大于常规矫治组（P < 0.01），提示干预措施有效，见表1。
表 1 常规矫治矫治组和干预矫治组矫治前后CEJ-AC情况[（$ \bar{x} \pm s $ ），mm]Table 1. CEJ-AC before and after treatment in the non-intervention group and the intervention group[（$ \bar{x} \pm s $ ），mm]组别 n（颗） 治疗前 治疗后 治疗前后差值 ｔ Ｐ 常规矫治组 32 3.30 ± 1.91 3.43 ± 1.63 −0.13 ± 0.11 −1.25 0.220 干预矫治组 22 3.63 ± 1.58 3.15 ± 1.32 0.48 ± 0.12 4.01 0.001* ｔ −0.66 0.68 3.79 Ｐ 0.515 0.499 < 0.001* *P < 0.05。 2.3 牙龈生物型对CEJ-AC的影响
矫治前后，薄龈型低位尖牙患者的CEJ-AC变化，差异无统计学意义（P > 0.05），干预组厚龈型低位尖牙患者的CEJ-AC降低（P < 0.05），且变化值同常规矫治组相比，差异有统计学意义（P < 0.05），见表2。
表 2 干预措施对不同牙龈型矫治前后CEJ-AC的影响[（$ \bar{x} \pm s $ ），mm]Table 2. Effect of interventions on CEJ-AC before and after treatment with different gingival type [（$ \bar{x} \pm s $ ），mm]组别 n（颗） 治疗前 治疗后 治疗前后差值 ｔ Ｐ 薄龈型 常规矫治组 19 3.32 ± 2.05 3.57 ± 1.71 −0.25 ± 0.16 −1.59 0.129 干预矫治组 12 3.39 ± 1.47 3.22 ± 1.31 0.18 ± 0.11 1.64 0.129 t −0.10 0.61 1.98 P 0.918 0.547 0.058 厚龈型 常规矫治组 13 3.28 ± 1.76 3.24 ± 1.55 0.04 ± 0.11 0.34 0.743 干预矫治组 10 3.91 ± 1.73 3.07 ± 1.39 0.84 ± 0.17 4.92 0.001* t −0.86 0.27 4.04 P 0.400 0.790 0.001* *P < 0.05。 2.4 矫治方式对CEJ-AC的影响
固定矫治的低位尖牙患者，干预组矫治后CEJ-AC值降低（P < 0.05），常规矫治组的CEJ-AC值变化差异无统计学意义（P > 0.05），干预组治疗前后的CEJ-AC差值大于常规矫治组（P < 0.05）；隐形矫治的低位尖牙患者，干预组矫治后的CEJ-AC降低值大于常规矫治组（P < 0.05），见表3。
表 3 干预措施对不同矫治方式矫治前后CEJ-AC的影响[（$\bar{x} \pm s $ ），mm]Table 3. Effect of interventions on CEJ-AC before and after treatment with different treatment methods [（$\bar{x} \pm s $ ），mm]组别 n（颗） 治疗前 治疗后 治疗前后差值 ｔ Ｐ 固定矫治 常规矫治组 26 3.38±1.88 3.47±1.61 0.10±0.11 0.81 0.428 干预矫治组 14 3.12±1.35 2.73±1.17 −0.39±0.10 −3.65 0.003* t 0.45 1.52 2.69 P 0.657 0.137 0.010* 隐形矫治 常规矫治组 6 2.98±2.17 3.27±1.84 0.28±0.22 1.27 0.259 干预矫治组 8 4.51±1.62 3.89±1.28 −0.63±0.27 −2.29 0.055 t −1.51 −0.75 2.45 P 0.156 0.470 0.030* *P < 0.05。 3. 讨论
牙列拥挤病例中非常常见的唇向低位尖牙属于咬合功能低下牙，失去正常咬合力的维持，其牙体牙周会出现如牙周膜和牙槽骨的退行性改变[11]。牙槽嵴顶的位置，即釉牙骨质界到牙槽嵴顶的距离（CEJ-AC）是正畸、正颌医师为规避牙周风险如牙龈退缩、牙槽骨吸收等十分关注的解剖因素[12]。研究认为CEJ-AC距离为2 mm以内[13]。有许多研究表明CBCT可准确提供牙周缺损的三维形态，优于传统的口腔X线片[14]。课题组选取的患者年龄在18～40岁，治疗前牙周情况均符合矫治标准，采用CBCT测量CEJ-AC，43例患者治疗前CEJ-AC的平均值为3.44 mm（95%CI：2.95～3.92），提示唇向低位尖牙牙槽嵴顶位置偏低，具有牙槽骨量不足的缺陷，在正畸过程中易出现牙槽骨吸收。这与课题组在前期的研究中发现，低位尖牙的患者正畸治疗后更容易出现牙龈退缩[9]结果相一致。
动物实验报道，咬合功能低下牙齿移动过程中PDL和血管细胞发生凋亡[15]，牙周组织易发生退行性变。基础研究发现通过恢复咬合功能干预，牙周膜结构、松质骨和皮质骨骨密度有所恢复[8]，还能通过增加 IGF-1和其受体诱导牙周膜细胞增殖[16]。数字化设计无托槽隐形矫治器有可精确施力的特点，课题组对上颌低位尖牙设计了干预措施：给予所选牙沿长轴方向压低0.1 mm的移动量的力，每日佩戴4 h，即给予牙齿间断力，连续佩戴3个月后开始常规矫治。这样牙周膜受轻力刺激，但基本不产生牙齿的移动。对照组则直接进行常规矫治。本研究选取上颌唇向低位尖牙进行研究，结果显示：干预措施组与常规矫治组治疗前CEJ-AC无组间差异；但矫治后，干预组CEJ-AC降低（P < 0.05），而常规矫治组CEJ-AC与矫治前无差别，提示干预措施有效，干预措施减少了上颌唇向低位牙矫治造成的牙槽骨量的丧失。
牙龈厚度是牙龈退缩发生的相关因素。Marziyeh 等[17]评估出牙龈生物型与牙槽骨厚度成正相关，牙龈越薄牙槽骨也越薄。而薄龈型患者正畸后牙龈退缩发生率更高[9，18]。课题组也探索了干预措施与牙龈生物型对治疗后牙槽骨丧失的作用，提示：干预措施对上颌厚牙龈型唇向低位牙牙槽骨吸收干预有效，对薄龈型未见明显效果。上颌薄龈型唇向低位尖牙患者对应更少的牙槽骨和牙龈量，在正畸力作用后，更容易发生缺失，尚需寻求其他干预措施提高正畸治疗的安全性。
固定矫治使用的托槽和弓丝等影响口腔清洁，引起菌斑积聚，易形成牙周组织炎症[19]。隐形矫治因其刷牙和进食可摘戴，对口腔清洁影响小，但其包裹性强，摘戴时产生力量大，对牙周的影响有争议[20]。在本研究中，干预措施运用于两种不同矫治方式的治疗中，发现固定矫治上颌低位尖牙患者，干预措施矫治后CEJ-AC值降低（P < 0.05），治疗前后的CEJ-AC差值大于常规矫治组（P < 0.05），提示干预措施有效；隐形矫治的低位尖牙患者，干预组矫治前后的CEJ-AC降低值大于常规矫治组（P < 0.05），也提示干预措施有效。
课题组通过对上颌唇向低位尖牙进行数字化设计无托槽矫治器进行治疗前干预，发现干预措施对厚龈型患者矫治后的CEJ-AC有改善作用，但对薄龈型无明显作用；在固定矫治或隐形矫治前进行干预，均有效果。
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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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![](data:image/svg+xml,<svg xmlns='http://www.w3.org/2000/svg' width='210' height='179'><foreignObject width='2000' height='100%'><div xmlns='http://www.w3.org/1999/xhtml' style='font-size:16px;font-family:Helvetica'><table>
<thead>
<tr>
<td class="table_top_border table_bottom_border2" style="width:15%" align="left" valign="middle">机构</td>
<td class="table_top_border table_bottom_border2" style="width:5%" align="center" valign="middle">年份</td>
<td class="table_top_border table_bottom_border2" style="width:15%" align="center" valign="middle">SSRIs</td>
<td class="table_top_border table_bottom_border2" style="width:5%" align="center" valign="middle">SNRIs</td>
<td class="table_top_border table_bottom_border2" style="width:20%" align="center" valign="middle">建议</td>
<td class="table_top_border table_bottom_border2" style="width:5%" align="center" valign="middle">参考文献</td>
<td class="table_top_border table_bottom_border2" style="width:20%" align="center" valign="middle">用药依据</td>
<td class="table_top_border table_bottom_border2" style="width:5%;" align="center" valign="middle">指南依据的文献</td>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">CSBM</td>
<td align="center" valign="middle">2022</td>
<td align="left" valign="middle">SSRIs类（首选） <br></td>
<td align="center" valign="middle">—</td>
<td align="left" valign="middle">遵循抗抑郁药与心理治疗并重的原则</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b33" ref-type="bibr">33</a></span>]</sup></td>
<td align="left" valign="middle">SSRIs类疗效及安全<br>性有循证医学证据支持</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b34" ref-type="bibr">34</a></span>]</sup></td>
</tr>
<tr>
<td align="left" valign="middle">APA</td>
<td align="center" valign="middle">2021</td>
<td align="left" valign="middle">氟西汀</td>
<td align="center" valign="middle">—</td>
<td align="left" valign="middle">建议联合心理治疗</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b30" ref-type="bibr">30</a></span>]</sup> <br></td>
<td align="left" valign="middle">伦理原则和行为准则</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b35" ref-type="bibr">35</a></span>]</sup></td>
</tr>
<tr>
<td align="left" valign="middle">RANZCP</td>
<td align="center" valign="middle">2021</td>
<td align="left" valign="middle">氟西汀</td>
<td align="center" valign="middle">—</td>
<td align="left" valign="middle">心理治疗为一线治疗</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b32" ref-type="bibr">32</a></span>]</sup></td>
<td align="left" valign="middle">有抗抑郁药物（氟西汀）对青少年患者有效的一级证据</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b36" ref-type="bibr">36</a></span>]</sup></td>
</tr>
<tr>
<td align="left" valign="middle">KSAD、KCNP</td>
<td align="center" valign="middle">2021</td>
<td align="left" valign="middle">艾司西酞普兰（首选）、氟西汀、舍曲林</td>
<td align="center" valign="middle">—</td>
<td align="left" valign="middle">用于轻中度抑郁发作的青少年</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b25" ref-type="bibr">25</a></span>]</sup></td>
<td align="left" valign="middle">氟西汀和舍曲林疗效显著</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b37" ref-type="bibr">37</a></span>]</sup></td>
</tr>
<tr>
<td align="left" valign="middle">JSCNP（未特别提及青少年抑郁症）</td>
<td align="center" valign="middle">2020</td>
<td align="left" valign="middle">艾司西酞普兰、舍曲林</td>
<td align="center" valign="middle">度洛西汀、文拉法辛</td>
<td align="left" valign="middle">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）。</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b26" ref-type="bibr">26</a></span>]</sup></td>
<td align="left" valign="middle">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 <br></td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b28" ref-type="bibr">28</a></span>，<span class="xref"><a href="#b38" ref-type="bibr">38</a></span>−<span class="xref"><a href="#b39" ref-type="bibr">39</a></span>]</sup></td>
</tr>
<tr>
<td align="left" valign="middle">AFPBN<br>（未特别提及<br>青少年抑郁症）</td>
<td align="center" valign="middle">2019</td>
<td align="left" valign="middle">SSRIs类 <br></td>
<td align="center" valign="middle">SNRIs</td>
<td align="left" valign="middle">无论临床严重程度如何，SSRIs及SNRIs均被认为是一线治疗药物</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b27" ref-type="bibr">27</a></span>]</sup></td>
<td align="left" valign="middle">三环类抗抑郁药、米氮平或米安色林可增强SRRIs<br>疗效</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b40" ref-type="bibr">40</a></span>−<span class="xref"><a href="#b41" ref-type="bibr">41</a></span>]</sup> <br></td>
</tr>
<tr>
<td align="left" valign="middle">NICE</td>
<td align="center" valign="middle">2019</td>
<td align="left" valign="middle">氟西汀</td>
<td align="center" valign="middle">—</td>
<td align="left" valign="middle">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</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b31" ref-type="bibr">31</a></span>]</sup></td>
<td align="left" valign="middle">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</td>
<td align="center" valign="middle">—</td>
</tr>
<tr>
<td align="left" valign="middle">CANMAT</td>
<td align="center" valign="middle">2016</td>
<td align="left" valign="middle">SSRIs类</td>
<td align="center" valign="middle">—</td>
<td align="left" valign="middle">SSRIs会增加青少年自杀风险，建议谨慎使用并密切监测</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b28" ref-type="bibr">28</a></span>]</sup> <br></td>
<td align="left" valign="middle">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。</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b42" ref-type="bibr">42</a></span>−<span class="xref"><a href="#b43" ref-type="bibr">43</a></span>]</sup> <br></td>
</tr>
<tr>
<td align="left" valign="middle">GLAD-PC</td>
<td align="center" valign="middle">2015</td>
<td align="left" valign="middle">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</td>
<td align="center" valign="middle">—</td>
<td align="left" valign="middle">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</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b22" ref-type="bibr">22</a></span>]</sup></td>
<td align="left" valign="middle">根据青少年患者的临床表现、医生的处方偏好</td>
<td align="center" valign="middle"><sup>[<span class="xref"><a href="#b44" ref-type="bibr">44</a></span>]</sup></td>
</tr>
<tr>
<td class="table_bottom_border" align="left" valign="middle">WFSBP</td>
<td class="table_bottom_border" align="center" valign="middle">2015</td>
<td class="table_bottom_border" align="left" valign="middle">氟西汀、舍曲林</td>
<td class="table_bottom_border" align="center" valign="middle">文拉法辛</td>
<td class="table_bottom_border" align="left" valign="middle">—</td>
<td class="table_bottom_border" align="center" valign="middle"><sup>[<span class="xref"><a href="#b24" ref-type="bibr">24</a></span>]</sup></td>
<td class="table_bottom_border" align="left" valign="middle">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。</td>
<td class="table_bottom_border" align="center" valign="middle"><sup>[<span class="xref"><a href="#b45" ref-type="bibr">45</a></span>−<span class="xref"><a href="#b47" ref-type="bibr">47</a></span>]</sup> <br></td>
</tr>
</tbody>
<tfoot>
<tr>
<td colspan="8" align="left" valign="middle"> 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。</td>
</tr>
</tfoot>
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