Stewart Richard M, Hood Sean D, Rao Pradeep, Moore Julia K, Runions Kevin C, Murphy Susannah E, Wong Janice W Y, Zepf Florian D
Centre & Discipline of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Divisions of Paediatrics and Psychiatry, UWA Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, 35 Stirling Highway (M561), Crawley WA, Perth, 6009, Australia.
Division of Psychiatry, UWA Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Australia.
Trials. 2018 Aug 10;19(1):434. doi: 10.1186/s13063-018-2791-4.
Selective serotonin reuptake inhibitors (SSRIs) are amongst the most prescribed antidepressants for adolescents with depressive symptoms and major depressive disorder. However, SSRIs have significant shortcomings as a first-line treatment considering that not all patients respond to these antidepressants. Amongst paediatric populations, meta-analyses indicate that up to approximately 40% of patients do not respond, and for those who do show benefit, there is substantial heterogeneity in response onset. The neurotransmitter serotonin (5-HT) plays a role in the clinical effectiveness and mechanisms of action of SSRIs. However, the exact and complete mechanism of action and reasons for the low response rate to SSRIs in some adolescent populations remains unknown.
To examine SSRI response and the role of 5-HT, this study will employ a randomised double-blind within subject, repeated measures design, recruiting adolescent patients with major depressive disorder. Participants will be subjected to acute tryptophan depletion (ATD) and the balanced control condition on two separate study days within a first study phase (Phase A), and the order in which these conditions (ATD/balanced control condition) occur will be random. This phase will be followed by Phase B, where participants will receive open label pharmacological treatment as usual with the SSRI fluoxetine and followed-up over a 12-week period.
ATD is a neurodietary method typically used to investigate the impact of lowered brain 5-HT synthesis on mood and behaviour. The major hypothesis of this study is that ATD will be negatively associated with mood and cognitive functioning, therefore reflecting individual serotonergic sensitivity and related depressive symptoms. Additionally, we expect the aforementioned effects of ATD administration on mood to predict clinical improvement with regard to overall depressive symptomatology 12 weeks into SSRI treatment.
Australian and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616001561471 . Registered on 11 November 2016.
选择性5-羟色胺再摄取抑制剂（SSRIs）是针对有抑郁症状和重度抑郁症的青少年患者最常开具的抗抑郁药物之一。然而，考虑到并非所有患者对这些抗抑郁药物都有反应，SSRIs作为一线治疗方法存在显著缺点。在儿科人群中，荟萃分析表明，高达约40%的患者没有反应，而对于那些确实显示出疗效的患者，反应起效时间存在很大差异。神经递质5-羟色胺（5-HT）在SSRIs的临床疗效和作用机制中发挥作用。然而，在一些青少年人群中，SSRIs的确切和完整作用机制以及低反应率的原因仍然未知。
为了研究SSRIs反应及5-HT的作用，本研究将采用随机双盲受试者内重复测量设计，招募患有重度抑郁症的青少年患者。在第一个研究阶段（A阶段）的两个不同研究日，参与者将接受急性色氨酸耗竭（ATD）和平衡对照条件，这些条件（ATD/平衡对照条件）出现的顺序将是随机的。此阶段之后是B阶段，参与者将接受开放标签的常规药物治疗，使用SSRI氟西汀，并在12周内进行随访。
ATD是一种神经饮食方法，通常用于研究降低大脑5-HT合成对情绪和行为的影响。本研究的主要假设是，ATD将与情绪和认知功能呈负相关，因此反映个体5-羟色胺能敏感性和相关抑郁症状。此外，我们预计ATD给药对情绪的上述影响能够预测在SSRIs治疗12周时总体抑郁症状的临床改善情况。
澳大利亚和新西兰临床试验注册中心（ANZCTR）ACTRN12616001561471。于2016年11月11日注册。
