The addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): a randomised, double-blind, placebo-controlled, multicentre clinical trial
The addition of fluoxetine to cognitive behavioural therapy for youth depression (YoDA-C): a randomised, double-blind, placebo-controlled, multicentre clinical trial
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DOI：
10.1016/s2215-0366(19)30215-9
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发表时间：
2019-09-01
影响因子：
64.3
通讯作者：
Berk, Michael
中科院分区：
文献类型：
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作者：
Davey, Christopher G.;Chanen, Andrew M.;Berk, Michael
药物通常用于治疗青少年抑郁症，但药物是否应该加入认知行为疗法（CBT）作为一线治疗尚不清楚。我们的目的是检查CBT和氟西汀联合治疗是否比CBT和安慰剂对中重度抑郁症的青少年更有效。方法青年抑郁缓解联合治疗（YoDA-C）试验是一项随机、双盲、安慰剂对照的多中心临床试验。参与者年龄在15-25岁之间，患有中度至重度重度抑郁症，并在澳大利亚墨尔本大都会的四个临床中心之一寻求治疗。患者被随机分配（1:1）接受CBT治疗12周，外加氟西汀或安慰剂。参与者开始每天服用一粒20毫克的氟西汀胶囊或一粒安慰剂。所有参与者都接受CBT治疗，由治疗师每周进行50分钟的治疗，并在基线、第4周、第8周和第12周参加访谈，在此期间，他们与研究助理一起完成评估。参与者在同一时间点去看精神病医生或精神病学培训生，以完成医疗评估。主要结果是12周时访谈者评定的蒙哥马利-阿斯伯格抑郁评定量表（MADRS）得分的变化。该试验已在澳大利亚新西兰临床试验登记处注册（ACTRN12612001281886）。研究结果：2013年2月20日至2016年12月13日，153名参与者（平均年龄19.6岁[SD 2.7]）入组。77例（50%）患者被分配到CBT和安慰剂组，76例（50%）患者被分配到CBT和氟西汀组。参与者在基线时患有严重抑郁症（CBT和安慰剂组平均MADRS评分为33.6 [SD 5.1]， CBT和氟西汀组平均MADRS评分为32.2[5.6]），有高比例的参与者患有焦虑症共病（CBT和安慰剂组为47 [61%]，CBT和氟西汀组为49[64%]）和过去一个月的自杀意念（CBT和安慰剂组为55 [71%]，CBT和氟西汀组为59[78%]）。CBT和安慰剂组59名（77%）参与者和CBT和氟西汀组64名（84%）参与者在第12周完成随访。治疗12周后，两组均显示MADRS评分降低（CBT和安慰剂组为-13.7,95% CI为-16.0至-11.4，CBT和氟西汀组为-15.1,-17.4至-12.9）。MADRS评分组间差异无统计学意义（-1.4,-4.7 ~ 1.8;p=0.39）。CBT组和安慰剂组有5例自杀企图，UST组和氟西汀组有1例自杀企图（比值比为0.2,0.0-1.8;p=0.21），其他自杀行为组间无显著差异。我们没有发现证据表明在CBT中加入氟西汀（而不是安慰剂）可以进一步减轻患有中重度重度重度抑郁症的年轻人的抑郁症状。探索性分析表明，增加药物治疗可能对合并焦虑症状的患者和年龄较大的青年有帮助。Elsevier Ltd.版权所有版权所有。
Background Medication is commonly used to treat youth depression, but whether medication should be added to cognitive behavioural therapy (CBT) as first-line treatment is unclear. We aimed to examine whether combined treatment with CBT and fluoxetine was more effective than CBT and placebo in youth with moderate-to-severe major depressive disorder.Methods The Youth Depression Alleviation-Combined Treatment (YoDA-C) trial was a randomised, double-blind, placebo-controlled, multicentre clinical trial. Participants were aged 15-25 years with moderate-to-severe MDD and had sought care at one of four clinical centres in metropolitan Melbourne, Australia. Patients were randomly assigned (1:1) to receive CBT for 12 weeks, plus either fluoxetine or placebo. Participants began on one 20 mg capsule of fluoxetine or one placebo pill per day. All participants received CBT, delivered by therapists in weekly 50-minute sessions and attended interviews at baseline, and at weeks 4, 8, and 12, during which they completed assessments with research assistants. Participants saw a psychiatrist or psychiatry trainee to complete medical assessments at the same timepoints. The primary outcome was change in the interviewer-rated Montgomery-Asberg Depression Rating Scale (MADRS) score at 12 weeks. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612001281886).Findings 153 participants (mean age 19.6 years [SD 2.7]) were enrolled from Feb 20, 2013, to Dec 13, 2016. 77 (50%) patients were allocated to CBT and placebo and 76 (50%) to CBT and fluoxetine. Participants had severe depression at baseline (mean MADRS score 33.6 [SD 5.1] in the CBT and placebo group and 32.2 [5.6] in the CBT and fluoxetine group), with high proportions of participants with anxiety disorder comorbidity (47 [61%] in the CBT and placebo group and 49 [64%] in the CBT and fluoxetine group) and past-month suicidal ideation (55 [71%] in the CBT and placebo group and 59 [78%] in the CBT and fluoxetine group). 59 (77%) participants in the CBT and placebo group and 64 (84%) in the CBT and fluoxetine group completed follow-up at week 12. After 12 weeks of treatment both groups showed a reduction in MADRS scores (-13.7, 95% CI -16.0 to -11.4, in the CBT and placebo group and -15.1, -17.4 to -12.9, in the CBT and fluoxetine group). There was no significant between-group difference in MADRS scores (-1.4, -4.7 to 1.8; p=0.39). There were five suicide attempts in the CBT and placebo group and one suicide attempt in the UST and fluoxetine group (odds ratio 0.2, 0.0-1.8; p=0.21), and no significant between-group differences for other suicidal behaviours.Interpretation We did not find evidence that the addition of fluoxetine (rather than placebo) to CBT further reduced depressive symptoms in young people with moderate-to-severe MDD. Exploratory analyses showed that the addition of medication might be helpful for patients with comorbid anxiety symptoms and for older youth. Copyright (C) 2019 Elsevier Ltd. All rights reserved.