Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden2Division of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Division of Psychology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden3Osher Center for Integrative Medicine, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
JAMA Psychiatry. 2015 Jul;72(7):659-67. doi: 10.1001/jamapsychiatry.2015.0546.
It is unclear whether d-cycloserine (DCS), a partial N-methyl-d-aspartate agonist that enhances fear extinction, can augment the effects of exposure-based cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD).
To examine whether DCS augments the effects of CBT for OCD and to explore (post hoc) whether concomitant antidepressant medication moderates the effects of DCS.
DESIGN, SETTING, AND PARTICIPANTS: A 12-week, double-blind randomized clinical trial with 3-month follow-up conducted at an academic medical center between September 4, 2012, and September 26, 2013. Participants included 128 adult outpatients with a primary diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of 16 or higher. Concurrent antidepressant medication was permitted if the dose had been stable for at least 2 months prior to enrollment and remained unchanged during the trial. The main analysis was by intention-to-treat population.
All participants received a previously validated Internet-based CBT protocol over 12 weeks and were randomized to receive either 50 mg of DCS or placebo, administered 1 hour before each of 5 exposure and response prevention tasks.
Clinician-administered Y-BOCS score at week 12 and at 3-month follow-up. Remission was defined as a score of 12 or lower on the Y-BOCS.
In the primary intention-to-treat analyses, DCS did not augment the effects of CBT compared with placebo (mean [SD] clinician-rated Y-BOCS score, DCS: 13.86 [6.50] at week 12 and 12.35 [7.75] at 3-month follow-up; placebo: 11.77 [5.95] at week 12 and 12.37 [6.68] at 3-month follow-up) but showed a significant interaction with antidepressants (clinician-rated Y-BOCS, B = -1.08; Z = -2.79; P = .005). Post hoc analyses revealed that antidepressants significantly impaired treatment response in the DCS group but not the placebo group, at both posttreatment and follow-up (clinician-rated Y-BOCS: t62 = -3.00; P = .004; and t61 = -3.49; P < .001, respectively). In the DCS group, a significantly greater proportion of antidepressant-free patients achieved remission status at follow-up (60% [95% CI, 45%-74%]) than antidepressant-medicated patients (24% [95% CI, 9%-48%]) (P = .008). Antidepressants had no effect in the placebo group (50% [95% CI, 36%-64%] remission rate in both groups).
The findings suggest that antidepressants may interact with DCS to block its facilitating effect on fear extinction. Use of DCS may be a promising CBT augmentation strategy but only in antidepressant-free patients with OCD.
clinicaltrials.gov Identifier: NCT01649895.
重要性：目前尚不清楚 D-环丝氨酸（DCS）是否可以增强恐惧消退，DCS 是一种部分 N-甲基-D-天冬氨酸激动剂，是否可以增强暴露为基础的认知行为疗法（CBT）对强迫症（OCD）的作用。
目的：检查 DCS 是否可以增强 OCD 的 CBT 效果，并探讨（事后分析）同时使用抗抑郁药是否可以调节 DCS 的效果。
设计、设置和参与者：这是一项在学术医疗中心进行的为期 12 周的双盲随机临床试验，随访期为 3 个月。研究对象为 128 名患有 OCD 的成年门诊患者，耶鲁-布朗强迫量表（Y-BOCS）评分在 16 分或以上。如果在入组前 2 个月内剂量稳定且在试验期间未改变，可同时使用抗抑郁药。主要分析是根据意向治疗人群进行的。
干预措施：所有参与者都接受了先前验证过的基于互联网的 CBT 方案 12 周，并随机接受 50 毫克 DCS 或安慰剂治疗，在 5 次暴露和反应预防任务前 1 小时服用。
主要结局和测量指标：第 12 周和 3 个月随访时的临床医生评定的 Y-BOCS 评分。缓解定义为 Y-BOCS 评分在 12 分或以下。
结果：在主要的意向治疗分析中，与安慰剂相比，DCS 并没有增强 CBT 的效果（临床医生评定的 Y-BOCS 评分的平均值[标准差]，DCS：第 12 周为 13.86[6.50]，第 3 个月随访为 12.35[7.75]；安慰剂：第 12 周为 11.77[5.95]，第 3 个月随访为 12.37[6.68]），但与抗抑郁药存在显著的交互作用（临床医生评定的 Y-BOCS，B=1.08；Z=-2.79；P=0.005）。事后分析显示，抗抑郁药在 DCS 组中显著降低了治疗反应，而在安慰剂组中没有，无论是在治疗后还是随访时（临床医生评定的 Y-BOCS：t62=-3.00；P=0.004；t61=-3.49；P<0.001）。在 DCS 组中，无抗抑郁药的患者在随访时达到缓解状态的比例显著高于有抗抑郁药的患者（60%[95%CI，45%-74%]比 24%[95%CI，9%-48%]）（P=0.008）。安慰剂组没有这种影响（两组的缓解率均为 50%[95%CI，36%-64%]）。
结论和相关性：研究结果表明，抗抑郁药可能与 DCS 相互作用，阻止其对恐惧消退的促进作用。在没有抗抑郁药的强迫症患者中，使用 DCS 可能是一种有前途的 CBT 增强策略。
试验注册：clinicaltrials.gov 标识符：NCT01649895。
