Clinical Effectiveness of Training for Awareness Resilience and Action Online Compared to Standard Treatment for Adolescents and Young Adults With Depression: Study Protocol and Analysis Plan for a Pragmatic, Multi-Center Randomized Controlled Superiority Trial

Abstract

Depression in adolescents and young adults is an increasing global health concern. Available treatments are not sufficiently effective and relapse rates remain high. The novel group-treatment program “Training for Awareness, Resilience and Action” (TARA) targets specific mechanisms based on neuroscientific findings in adolescent depression. TARA is framed within the National Institute of Mental Health's Research Domain Criteria and has documented feasibility and preliminary efficacy in the treatment of adolescent depression. Since neurodevelopment continues well into the mid-twenties, age-adapted treatments are warranted also for young adults. Patients 15–22 years old, with either major depressive disorder (MDD) or persistent depressive disorder (PDD) according to the DSM-IV/5 or a rating >40 on the clinician rating scale Children's Depression Rating Scale—Revised (CDRS-R), will be recruited from specialized Child and Adolescent Psychiatry and local Youth-Clinics and randomized to either TARA or standard treatment, including but not limited to antidepressant medication and/or psychotherapy. Outcome measures will be obtained before randomization (T0), after 3 months of treatment (T1) and at 6-months- (T2) and 24-months- (T3) follow-up. Additionally, dose-response measures will be obtained weekly in the TARA-arm and measures for mediation-analysis will be obtained halfway through treatment (T0.5). Primary outcome measure is Reynolds Adolescent Depression Scale (RADS-2) score at T1. Secondary outcome measures include RADS-2 score at T2, Multidimensional Anxiety Scale for Children at T1 and T2, and CDRS-R at T1. Additional outcome measures include self-report measures of depression-associated symptoms, systemic bio-indicators of depression from blood and hair, heartrate variability, brain magnetic resonance imaging, as well as three-axial accelerometry for sleep-objectivization. Qualitative data will be gathered to reach a more comprehensive understanding of the factors affecting adolescents and young adults with depression and the extent to which the different treatments address these factors. In summary, this article describes the design, methods and statistical analysis plan for pragmatically evaluating the clinical effectiveness of TARA. This will be the first RCT to examine the effects of TARA compared to standard treatment for adolescents and young adults with MDD or PDD. We argue that this study will extend the current knowledgebase regarding the treatment of depression.NCT Registration: identifier [NCT04747340].

Psychometric properties of the Swedish version of the Reynolds Adolescent Depression Scale second edition (RADS-2) in a clinical sample

“…In that sample measurement, invariance was also confirmed for sex and age-group [20]. Since the scale is intended for clinical application [10] and since valid outcome-measures are needed for both ongoing and future clinical trials, including in participants from a wider age-range than previously studied [9], we here present data on the psychometric properties of RADS-2 in a heterogenous clinical sample with affective symptomatology.…”

“…For example, the Diagnostic and Statistical Manual of Mental disorders, fifth edition (DSM-5) allows for the replacement of depressed mood with irritability as a core diagnostic symptom criterion [6]. At the same time, both pathophysiological and neurodevelopmental similarities are shared between teenagers and adults up to their mid-twenties [7,8], which has warranted research spanning across this critical age-range [9]. In the evaluation of symptom severity and treatment effectiveness for individual patients, as well as more broadly for research with national and international ambitions, measures of depression that are valid across different contexts, age-groups, and languages are clearly needed.…”

COVID-19 and mental health disorders in children and adolescents (Review)

“…This is followed by training in interoceptive awareness and techniques to develop metacognition, compassion and care for both the patient and others. The final step is value-based behavioral activation ( Ekbäck et al 2021 ). Specific target areas are sustained threats, sleep and arousal, and attention and cognitive control.…”

Clinical effectiveness of training for awareness, resilience, and action for adolescents and young adults with depression: The pilot phase of a multicenter randomized controlled trial

“…Subsequent targets are addressed progressively in a way that gives priority to the domains thought to be driving the psychopathology (18). The development process and a detailed description of the content of the different modules of TARA, as well as their relation to targeted constructs of the RDoC have been thoroughly elaborated in our previous publications in Frontiers' journals (18,20,21). For example, the proposed working mechanism of TARA in relation to the first target of sustained threat and amygdala hyper-reactivity includes practices to increase vagal afference.…”

“…Furthermore, the neuro-developmental trajectory of the cerebral cortex (26) suggests that adolescents and young adults share similarities that are rarely addressed in clinical trials, and very few studies have been conducted that cover the critical age-range of 15-22. To resolve remaining questions, we have planned and initiated a multicenter randomized controlled trial (RCT) (20), the pilot phase of which is reported here. Apart from an upcoming U.S. study that will use magnetic resonance imaging as primary outcome, the ISRCTN-and Clinicalrtrials.gov registers (as of February 2023) record no comparable recent nor ongoing trials anywhere in the world.…”