RESUMO
Background: Depression is a top-ranking global health concern increasing in magnitude. Available treatments for adolescents and young adults are not convincingly effective and relapse rates remain high. Training for Awareness, Resilience and Action (TARA) is a group treatment program targeting specific pathophysiological mechanisms of depression in young people. TARA is feasible, acceptable, preliminarily efficacious in depressed American adolescents, and it affects postulated brain-circuitry. Methods: As an initial step of a multicenter randomized controlled trial (RCT) we performed a single-arm multicenter pilot-study on TARA. Thirty-five depressed individuals (15-21 years old, 28 females) received TARA for 12 weeks face-to-face or online. Data was collected before (T0), during, and after the intervention (T1). The trial was pre-registered at clinicaltrials.gov, NCT Registration: identifier [NCT04747340]. Feasibility outcomes included recruitment, attendance rates, and session ratings. Adverse events were recorded weekly and extracted from medical records at the end of the trial. Primary effectiveness outcome was self-rated depression severity on Reynolds Adolescent Depression scale 2nd ed. at T1. Secondary outcomes were Children's Depression Rating Scale-revised (CDRS-R) and Multidimensional Anxiety Scale for Children (MASC) at T1. Results: TARA was feasible and safe in the present trial. No significant RADS-2-change was seen (adjusted mean difference -3.26, 95 % CI -8.35 to 1.83; p= 0.20), however a significant decrease in CDRS-R scores is reported (adjusted mean difference -9.99, 95% CI -14.76 to -5.22; p < 0.001). MASC-scores did not change significantly (adjusted mean difference 1.98, 95% CI -0.96 to 4.91; p=0.18). Additional feasibility aspects are presented and discussed. Discussion: Limitations include substantial loss-to-follow-up, no randomization to control, and that some participants received concomitant treatment(s). The Coronavirus pandemic complicated both implementation and interpretation of the trial. In conclusion TARA was feasible and safe in depressed adolescents and young adults. Preliminary signs of effectiveness were seen. The initiated RCT will be important and worthwhile to conduct, and several improvements to the design are suggested based on the present results. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04747340.
RESUMO
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].
