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© The Author(s). 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Background

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.

Methods

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.

Discussion

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.

Trial registration

Australian and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616001561471. Registered on 11 November 2016.

Details

Title
Using acute tryptophan depletion to investigate predictors of treatment response in adolescents with major depressive disorder: study protocol for a randomised controlled trial
Author
Stewart, Richard M. 1 ; Hood, Sean D. 2 ; Rao, Pradeep 3 ; Moore, Julia K. 4 ; Runions, Kevin C. 5 ; Murphy, Susannah E. 6 ; Wong, Janice W. Y. 7   VIAFID ORCID Logo  ; Zepf, Florian D. 7 

 The University of Western Australia, Centre & Discipline of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Divisions of Paediatrics and Psychiatry, UWA Medical School, Faculty of Health and Medical Sciences, Perth, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910) 
 The University of Western Australia, Division of Psychiatry, UWA Medical School, Faculty of Health and Medical Sciences, Perth, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910) 
 The University of Western Australia, Centre & Discipline of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Divisions of Paediatrics and Psychiatry, UWA Medical School, Faculty of Health and Medical Sciences, Perth, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); Community Child and Adolescent Mental Health Services (CAMHS), Department of Health in Western Australia, Perth, Australia (GRID:grid.1012.2) 
 The University of Western Australia, Centre & Discipline of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Divisions of Paediatrics and Psychiatry, UWA Medical School, Faculty of Health and Medical Sciences, Perth, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); Paediatric Consult-Liaison, Acute Child and Adolescent Mental Health Services (CAMHS), Department of Health, Perth, Australia (GRID:grid.413880.6) (ISNI:0000 0004 0453 2856) 
 The University of Western Australia, Centre & Discipline of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Divisions of Paediatrics and Psychiatry, UWA Medical School, Faculty of Health and Medical Sciences, Perth, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); Community Child and Adolescent Mental Health Services (CAMHS), Department of Health in Western Australia, Perth, Australia (GRID:grid.1012.2); Telethon Kids Institute, Perth, Australia (GRID:grid.414659.b) (ISNI:0000 0000 8828 1230) 
 University of Oxford, Department of Psychiatry, Warneford Hospital, Oxford, UK (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948) 
 The University of Western Australia, Centre & Discipline of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Divisions of Paediatrics and Psychiatry, UWA Medical School, Faculty of Health and Medical Sciences, Perth, Australia (GRID:grid.1012.2) (ISNI:0000 0004 1936 7910); Telethon Kids Institute, Perth, Australia (GRID:grid.414659.b) (ISNI:0000 0000 8828 1230); Specialised Child and Adolescent Mental Health Services (CAMHS), Department of Health in Western Australia, Perth, Australia (GRID:grid.414659.b) 
Pages
434
Publication year
2018
Publication date
Dec 2018
Publisher
BioMed Central
e-ISSN
17456215
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2795270065
Copyright
© The Author(s). 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.