Division of Psychiatry, UWA Medical School, The University of Western Australia, Perth, Australia.
J Psychopharmacol. 2017 Dec;31(12):1615-1623. doi: 10.1177/0269881117736916. Epub 2017 Nov 2.
Serotonergic antidepressants are first-line medication therapies for obsessive-compulsive disorder, however it is not known if synaptic serotonin availability is important for selective serotonin reuptake inhibitor efficacy. The present study tested the hypothesis that temporary reduction in central serotonin transmission, through acute tryptophan depletion, would result in an increase in anxiety in selective serotonin reuptake inhibitor-remitted obsessive-compulsive disorder patients.
Eight patients (four males) with obsessive-compulsive disorder who showed sustained clinical improvement with selective serotonin reuptake inhibitor treatment underwent acute tryptophan depletion in a randomized, double-blind, placebo-controlled, within-subjects design, over two days one week apart. Five hours after consumption of the depleting/sham drink the participants performed a personalized obsessive-compulsive disorder symptom exposure task. Psychological responses were measured using the Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and Visual Analogue Scales.
Free plasma tryptophan to large neutral amino acid ratio decreased by 93% on the depletion day and decreased by 1% on the sham day, as anticipated. Psychological rating scores as measured by Visual Analogue Scale showed a significant decrease in perceived control and increase in interfering thoughts at the time of provocation on the depletion day but not on the sham day. A measure of convergent validity, namely Visual Analogue Scale Similar to past, was significantly higher at the time of provocation on both the depletion and sham days. Both the depletion and time of provocation scores for Visual Analogue Scale Anxiety, Spielberger State Anxiety Inventory, Yale-Brown Obsessive Compulsive Scale and blood pressure were not significant.
Acute tryptophan depletion caused a significant decrease in perceived control and increase in interfering thoughts at the time of provocation. Acute tryptophan depletion had no effect on the Spielberger State Anxiety Inventory or Visual Analogue Scale Anxiety measures, which suggests that the mechanism of action of selective serotonin reuptake inhibitors may be different to that seen in panic, social anxiety and post-traumatic stress disorder. Successful selective serotonin reuptake inhibitor treatment of obsessive-compulsive disorder may involve the ability of serotonin to switch habitual responding to goal-directed behaviour.
5-羟色胺能抗抑郁药是强迫症的一线药物治疗方法，但尚不清楚突触 5-羟色胺的可用性是否对选择性 5-羟色胺再摄取抑制剂的疗效很重要。本研究通过急性色氨酸耗竭测试了这样一种假设，即中枢 5-羟色胺传递的暂时减少会导致选择性 5-羟色胺再摄取抑制剂缓解的强迫症患者焦虑增加。
在为期一周的时间内，8 名（4 名男性）强迫症患者在接受选择性 5-羟色胺再摄取抑制剂治疗后持续临床改善，接受了随机、双盲、安慰剂对照、自身对照设计的两次急性色氨酸耗竭试验。在消耗/假饮料摄入后 5 小时，参与者执行个性化强迫症症状暴露任务。使用 Spielberger 状态焦虑量表、耶鲁-布朗强迫症量表和视觉模拟量表测量心理反应。
如预期的那样，在消耗日游离血浆色氨酸与大中性氨基酸的比值降低了 93%，而在假日降低了 1%。视觉模拟量表的心理评分显示，在消耗日诱发时，自我控制感显著降低，干扰性思维增加，但在假日没有。在消耗和诱发时间时，视觉模拟量表相似于过去的一项收敛效度测量指标明显升高。视觉模拟量表焦虑、Spielberger 状态焦虑量表、耶鲁-布朗强迫症量表和血压的消耗和诱发分数均不显著。
急性色氨酸耗竭导致在诱发时自我控制感显著降低，干扰性思维增加。急性色氨酸耗竭对 Spielberger 状态焦虑量表或视觉模拟量表焦虑测量无影响，这表明选择性 5-羟色胺再摄取抑制剂的作用机制可能与惊恐、社交焦虑和创伤后应激障碍不同。成功的选择性 5-羟色胺再摄取抑制剂治疗强迫症可能涉及 5-羟色胺将习惯性反应转换为目标导向行为的能力。
