March John, Silva Susan, Petrycki Stephen, Curry John, Wells Karen, Fairbank John, Burns Barbara, Domino Marisa, McNulty Steven, Vitiello Benedetto, Severe Joanne
Duke Clinical Research Institute, Department of Psychiatry, Duke University Medical Center, Durham, NC 27710, USA.
JAMA. 2004 Aug 18;292(7):807-20. doi: 10.1001/jama.292.7.807.
Initial treatment of major depressive disorder in adolescents may include cognitive-behavioral therapy (CBT) or a selective serotonin reuptake inhibitor (SSRI). However, little is known about their relative or combined effectiveness.
To evaluate the effectiveness of 4 treatments among adolescents with major depressive disorder.
DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of a volunteer sample of 439 patients between the ages of 12 to 17 years with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of major depressive disorder. The trial was conducted at 13 US academic and community clinics between spring 2000 and summer 2003.
Twelve weeks of (1) fluoxetine alone (10 to 40 mg/d), (2) CBT alone, (3) CBT with fluoxetine (10 to 40 mg/d), or (4) placebo (equivalent to 10 to 40 mg/d). Placebo and fluoxetine alone were administered double-blind; CBT alone and CBT with fluoxetine were administered unblinded.
Children's Depression Rating Scale-Revised total score and, for responder analysis, a (dichotomized) Clinical Global Impressions improvement score.
Compared with placebo, the combination of fluoxetine with CBT was statistically significant (P =.001) on the Children's Depression Rating Scale-Revised. Compared with fluoxetine alone (P =.02) and CBT alone (P =.01), treatment of fluoxetine with CBT was superior. Fluoxetine alone is a superior treatment to CBT alone (P =.01). Rates of response for fluoxetine with CBT were 71.0% (95% confidence interval [CI], 62%-80%); fluoxetine alone, 60.6% (95% CI, 51%-70%); CBT alone, 43.2% (95% CI, 34%-52%); and placebo, 34.8% (95% CI, 26%-44%). On the Clinical Global Impressions improvement responder analysis, the 2 fluoxetine-containing conditions were statistically superior to CBT and to placebo. Clinically significant suicidal thinking, which was present in 29% of the sample at baseline, improved significantly in all 4 treatment groups. Fluoxetine with CBT showed the greatest reduction (P =.02). Seven (1.6%) of 439 patients attempted suicide; there were no completed suicides.
The combination of fluoxetine with CBT offered the most favorable tradeoff between benefit and risk for adolescents with major depressive disorder.
青少年重度抑郁症的初始治疗可能包括认知行为疗法（CBT）或选择性5-羟色胺再摄取抑制剂（SSRI）。然而，对于它们的相对疗效或联合疗效知之甚少。
评估4种治疗方法对青少年重度抑郁症的疗效。
设计、场所和参与者：对439例年龄在12至17岁、符合《精神疾病诊断与统计手册》第四版重度抑郁症初步诊断标准的志愿者进行随机对照试验。该试验于2000年春季至2003年夏季在美国13家学术和社区诊所进行。
为期12周的（1）单用氟西汀（10至40毫克/天），（2）单用CBT，（3）CBT联合氟西汀（10至40毫克/天），或（4）安慰剂（相当于10至40毫克/天）。安慰剂和单用氟西汀采用双盲给药；单用CBT和CBT联合氟西汀采用非盲给药。
儿童抑郁评定量表修订版总分，以及用于反应者分析的（二分法）临床总体印象改善评分。
与安慰剂相比，氟西汀联合CBT在儿童抑郁评定量表修订版上有统计学显著差异（P = 0.001）。与单用氟西汀（P = 0.02）和单用CBT（P = 0.01）相比，氟西汀联合CBT治疗效果更佳。单用氟西汀是比单用CBT更优的治疗方法（P = 0.01）。氟西汀联合CBT的反应率为71.0%（95%置信区间[CI]，62%-80%）；单用氟西汀为60.6%（95%CI，51%-70%）；单用CBT为43.2%（95%CI，34%-52%）；安慰剂为34.8%（95%CI，26%-44%）。在临床总体印象改善反应者分析中，两种含氟西汀的治疗方案在统计学上优于CBT和安慰剂。基线时29%的样本存在具有临床意义的自杀念头，在所有4个治疗组中均有显著改善。氟西汀联合CBT的降低幅度最大（P = 0.02）。439例患者中有7例（1.6%）自杀未遂；无自杀死亡病例。
对于青少年重度抑郁症患者，氟西汀联合CBT在获益与风险之间提供了最有利的权衡。
