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

Erik Ekbäck, Gabriel Granåsen, Rachel Svärling, Ida Blomqvist, Eva Henje, Erik Ekbäck, Gabriel Granåsen, Rachel Svärling, Ida Blomqvist, Eva Henje

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].

Keywords: adolescent depression; antidepressant drugs; biomarkers; psychotherapy; randomization; yoga; young adults.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Ekbäck, Granåsen, Svärling, Blomqvist and Henje.

Figures

Figure 1
Figure 1
Flow of participants.

References

    1. WHO . Depression and Other Common Mental Disorders: Global Health Estimates. World Health Organization; (2017).
    1. Lepine JP, Briley M. The increasing burden of depression. Neuropsychiatr Dis Treat. (2011) 7(Suppl 1):3–7. 10.2147/NDT.S19617
    1. Avenevoli S, Swendsen J, He JP, Burstein M, Merikangas KR. Major depression in the national comorbidity survey-adolescent supplement: prevalence, correlates, and treatment. J Am Acad Child Adolesc Psychiatry. (2015) 54:37–44.e2. 10.1016/j.jaac.2014.10.010
    1. Johnson D, Dupuis G, Piche J, Clayborne Z, Colman I. Adult mental health outcomes of adolescent depression: a systematic review. Depress Anxiety. (2018) 35:700–16. 10.1002/da.22777
    1. GBD-collaborators . Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. (2018) 392:1789–858. 10.1016/S0140-6736(18)32279-7
    1. Cox GR, Callahan P, Churchill R, Hunot V, Merry SN, Parker AG, et al. . Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents. Cochrane Database Syst Rev. (2014) 11:CD008324. 10.1002/14651858.CD008324.pub3
    1. Yuan S, Zhou X, Zhang Y, Zhang H, Pu J, Yang L, et al. . Comparative efficacy and acceptability of bibliotherapy for depression and anxiety disorders in children and adolescents: a meta-analysis of randomized clinical trials. Neuropsychiatr Dis Treat. (2018) 14:353–65. 10.2147/NDT.S152747
    1. Cipriani A, Zhou X, Del Giovane C, Hetrick SE, Qin B, Whittington C, et al. . Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet. (2016) 388:881–90. 10.1016/S0140-6736(16)30385-3
    1. Zhou X, Hetrick SE, Cuijpers P, Qin B, Barth J, Whittington CJ, et al. . Comparative efficacy and acceptability of psychotherapies for depression in children and adolescents: a systematic review and network meta-analysis. World Psychiatry. (2015) 14:207–22. 10.1002/wps.20217
    1. Pu J, Zhou X, Liu L, Zhang Y, Yang L, Yuan S, et al. . Efficacy and acceptability of interpersonal psychotherapy for depression in adolescents: a meta-analysis of randomized controlled trials. Psychiatry Res. (2017) 253:226–32. 10.1016/j.psychres.2017.03.023
    1. Yang L, Zhou X, Zhou C, Zhang Y, Pu J, Liu L, et al. . Efficacy and acceptability of cognitive behavioral therapy for depression in children: a systematic review and meta-analysis. Acad Pediatr. (2017) 17:9–16. 10.1016/j.acap.2016.08.002
    1. Yang TT, Simmons AN, Matthews SC, Tapert SF, Frank GK, Max JE, et al. . Adolescents with major depression demonstrate increased amygdala activation. J Am Acad Child Adolesc Psychiatry. (2010) 49:42–51. 10.1097/00004583-201001000-00008
    1. Connolly CG, Wu J, Ho TC, Hoeft F, Wolkowitz O, Eisendrath S, et al. . Resting-state functional connectivity of subgenual anterior cingulate cortex in depressed adolescents. Biol Psychiatry. (2013) 74:898–907. 10.1016/j.biopsych.2013.05.036
    1. Kerestes R, Davey CG, Stephanou K, Whittle S, Harrison BJ. Functional brain imaging studies of youth depression: a systematic review. Neuroimage Clin. (2014) 4:209–31. 10.1016/j.nicl.2013.11.009
    1. Heatherton TF. Neuroscience of self and self-regulation. Annu Rev Psychol. (2011) 62:363–90. 10.1146/annurev.psych.121208.131616
    1. Bebko G, Bertocci M, Chase H, Dwojak A, Bonar L, Almeida J, et al. . Decreased amygdala-insula resting state connectivity in behaviorally and emotionally dysregulated youth. Psychiatry Res. (2015) 231:77–86. 10.1016/j.pscychresns.2014.10.015
    1. Burghy CA, Stodola DE, Ruttle PL, Molloy EK, Armstrong JM, Oler JA, et al. . Developmental pathways to amygdala-prefrontal function and internalizing symptoms in adolescence. Nat Neurosci. (2012) 15:1736–41. 10.1038/nn.3257
    1. Connolly CG, Ho TC, Blom EH, LeWinn KZ, Sacchet MD, Tymofiyeva O, et al. . Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression. J Affect Disord. (2017) 207:86–94. 10.1016/j.jad.2016.09.026
    1. Cullen KR, Westlund MK, Klimes-Dougan B, Mueller BA, Houri A, Eberly LE, et al. . Abnormal amygdala resting-state functional connectivity in adolescent depression. JAMA Psychiatry. (2014) 71:1138–47. 10.1001/jamapsychiatry.2014.1087
    1. Grant MM, Cannistraci C, Hollon SD, Gore J, Shelton R. Childhood trauma history differentiates amygdala response to sad faces within MDD. J Psychiatr Res. (2011) 45:886–95. 10.1016/j.jpsychires.2010.12.004
    1. Gogtay N, Giedd JN, Lusk L, Hayashi KM, Greenstein D, Vaituzis AC, et al. . Dynamic mapping of human cortical development during childhood through early adulthood. Proc Natl Acad Sci U S A. (2004) 101:8174–9. 10.1073/pnas.0402680101
    1. Ahmed SP, Bittencourt-Hewitt A, Sebastian CL. Neurocognitive bases of emotion regulation development in adolescence. Dev Cogn Neurosci. (2015) 15:11–25. 10.1016/j.dcn.2015.07.006
    1. Shaw P, Kabani NJ, Lerch JP, Eckstrand K, Lenroot R, Gogtay N, et al. . Neurodevelopmental trajectories of the human cerebral cortex. J Neurosci. (2008) 28:3586–94. 10.1523/JNEUROSCI.5309-07.2008
    1. Yang TT, Simmons AN, Matthews SC, Tapert SF, Frank GK, Bischoff-Grethe A, et al. . Depressed adolescents demonstrate greater subgenual anterior cingulate activity. Neuroreport. (2009) 20:440–4. 10.1097/WNR.0b013e3283262e10
    1. Henje Blom E, Duncan LG, Ho TC, Connolly CG, LeWinn KZ, Chesney M, et al. . The development of an RDoC-based treatment program for adolescent depression: Training for Awareness, Resilience, and Action (TARA). Front Hum Neurosci. (2014) 8:630. 10.3389/fnhum.2014.00630
    1. Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K, et al. . Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. (2010) 167:748–51. 10.1176/appi.ajp.2010.09091379
    1. Henje Blom E, Tymofiyeva O, Chesney MA, Ho TC, Moran P, Connolly CG, et al. . Feasibility and preliminary efficacy of a novel RDoC-based treatment program for adolescent depression: Training for Awareness Resilience and Action (TARA)-A Pilot Study. Front Psychiatry. (2016) 7:208. 10.3389/fpsyt.2016.00208
    1. Tymofiyeva O, Henje E, Yuan JP, Huang CY, Connolly CG, Ho TC, et al. . Reduced anxiety and changes in amygdala network properties in adolescents with training for awareness, resilience, and action (TARA). Neuroimage Clin. (2020) 29:102521. 10.1016/j.nicl.2020.102521
    1. Yuan JP, Connolly CG, Henje E, Sugrue LP, Yang TT, Xu D, et al. . Gray matter changes in adolescents participating in a meditation training. Front Hum Neurosci. (2020) 14:319. 10.3389/fnhum.2020.00319
    1. Leone M, Kuja-Halkola R, Leval A, D'Onofrio BM, Larsson H, Lichtenstein P, et al. . Association of Youth depression with subsequent somatic diseases and premature death. JAMA Psychiatry. (2020) 78:302–10. 10.1001/jamapsychiatry.2020.3786
    1. Wolkowitz OM, Reus VI, Mellon SH. Of sound mind and body: depression, disease, and accelerated aging. Dialogues Clin Neurosci. (2011) 13:25–39. 10.31887/DCNS.2011.13.1/owolkowitz
    1. Plana-Ripoll O, Pedersen CB, Agerbo E, Holtz Y, Erlangsen A, Canudas-Romo V, et al. . A comprehensive analysis of mortality-related health metrics associated with mental disorders: a nationwide, register-based cohort study. Lancet. (2019) 394:1827–35. 10.1016/S0140-6736(19)32316-5
    1. Han LKM, Verhoeven JE, Tyrka AR, Penninx B, Wolkowitz OM, Månsson KNT, et al. . Accelerating research on biological aging and mental health: current challenges and future directions. Psychoneuroendocrinology. (2019) 106:293–311. 10.1016/j.psyneuen.2019.04.004
    1. Henje Blom E, Olsson EM, Serlachius E, Ericson M, Ingvar M. Heart rate variability (HRV) in adolescent females with anxiety disorders and major depressive disorder. Acta Paediatr. (2010) 99:604–11. 10.1111/j.1651-2227.2009.01657.x
    1. Paniccia M, Paniccia D, Thomas S, Taha T, Reed N. Clinical and non-clinical depression and anxiety in young people: a scoping review on heart rate variability. Auton Neurosci. (2017) 208:1–14. 10.1016/j.autneu.2017.08.008
    1. Zimmerman M, McGlinchey JB, Posternak MA, Friedman M, Attiullah N, Boerescu D. How should remission from depression be defined? The depressed patient's perspective. Am J Psychiatry. (2006) 163:148–50. 10.1176/appi.ajp.163.1.148
    1. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krleza-Jeric K, et al. . SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. (2013) 158:200–7. 10.7326/0003-4819-158-3-201302050-00583
    1. Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, et al. . CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. Bmj. (2010) 340:c869. 10.1136/bmj.c869
    1. Zwarenstein M, Treweek S, Gagnier JJ, Altman DG, Tunis S, Haynes B, et al. . Improving the reporting of pragmatic trials: an extension of the CONSORT statement. Bmj. (2008) 337:a2390. 10.1136/bmj.a2390
    1. Boutron I, Moher D, Altman DG, Schulz KF, Ravaud P. Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Intern Med. (2008) 148:295–309. 10.7326/0003-4819-148-4-200802190-00008
    1. Sheehan DV, Sheehan KH, Shytle RD, Janavs J, Bannon Y, Rogers JE, et al. . Reliability and validity of the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). J Clin Psychiatry. (2010) 71:313–26. 10.4088/JCP.09m05305whi
    1. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. . The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. (1998) 59(Suppl. 20):22–33;quiz 4–57.
    1. Hayes SC, Luoma JB, Bond FW, Masuda A, Lillis J. Acceptance and commitment therapy: model, processes and outcomes. Behav Res Ther. (2006) 44:1–25. 10.1016/j.brat.2005.06.006
    1. Bronfenbrenner U. Toward an experimental ecology of human development. Am Psychol. (1977) 32:513–31. 10.1037/0003-066X.32.7.513
    1. Socialstyrelsen . Nationella Riktlinjer för Vård vid Depression och Ångestsyndrom - Stöd för Styrning och Ledning(2017).
    1. Socialstyrelsen . Vård vid Depression Och ångestsyndrom 2019 - Underlagsrapport (2019).
    1. Högberg C, Billstedt E, Björck C, Björck PO, Ehlers S, Gustle LH, et al. . Diagnostic validity of the MINI-KID disorder classifications in specialized child and adolescent psychiatric outpatient clinics in Sweden. BMC Psychiatry. (2019) 19:142. 10.1186/s12888-019-2121-8
    1. Poznanski EO. Children's Depression Rating Scale-Revised (CDRS-R) Manual. Los Angeles, CA: Western Psychological Services; (1996). 76 p.
    1. Nilsson D, Svedin CG. Dissociation among Swedish adolescents and the connection to trauma: an evaluation of the Swedish version of Adolescent Dissociative Experience Scale. J Nerv Ment Dis. (2006) 194:684–9. 10.1097/01.nmd.0000235774.08690.dc
    1. Unden AL, Orth-Gomer K. Development of a social support instrument for use in population surveys. Soc Sci Med (1982). (1989) 29:1387–92. 10.1016/0277-9536(89)90240-2
    1. Spinhoven P, Penninx BW, Hickendorff M, van Hemert AM, Bernstein DP, Elzinga BM. Childhood Trauma Questionnaire: factor structure, measurement invariance, and validity across emotional disorders. Psychol Assess. (2014) 26:717–29. 10.1037/pas0000002
    1. Bernstein DP, Ahluvalia T, Pogge D, Handelsman L. Validity of the Childhood Trauma Questionnaire in an adolescent psychiatric population. J Am Acad Child Adolesc Psychiatry. (1997) 36:340–8. 10.1097/00004583-199703000-00012
    1. Felitti VJ, Anda RF, Nordenberg D, Williamson DF, Spitz AM, Edwards V, et al. . Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. (1998) 14:245–58. 10.1016/S0749-3797(98)00017-8
    1. Osman A, Gutierrez PM, Bagge CL, Fang Q, Emmerich A. Reynolds adolescent depression scale-second edition: a reliable and useful instrument. J Clin Psychol. (2010) 66:1324–45. 10.1002/jclp.20727
    1. Blomqvist I, Ekbäck E, Dennhag I, Henje E. Validation of the Swedish version of the Reynolds Adolescent Depression Scale second edition (RADS-2) in a normative sample. Nord J Psychiatry. (2020) 75:1–8. 10.1080/08039488.2020.1850858
    1. March JS, Parker JD, Sullivan K, Stallings P, Conners CK. The Multidimensional Anxiety Scale for Children (MASC): factor structure, reliability, and validity. J Am Acad Child Adolesc Psychiatry. (1997) 36:554–65. 10.1097/00004583-199704000-00019
    1. Ivarsson T. Normative data for the Multidimensional Anxiety Scale for Children (MASC) in Swedish adolescents. Nord J Psychiatry. (2006) 60:107–13. 10.1080/08039480600588067
    1. Ntini I, Vadlin S, Olofsdotter S, Ramklint M, Nilsson KW, Engström I, et al. . The Montgomery and Åsberg Depression Rating Scale - self-assessment for use in adolescents: an evaluation of psychometric and diagnostic accuracy. Nord J Psychiatry. (2020) 74:415–22. 10.1080/08039488.2020.1733077
    1. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. (1979) 134:382–9. 10.1192/bjp.134.4.382
    1. Briere J, Weathers FW, Runtz M. Is dissociation a multidimensional construct? Data from the Multiscale Dissociation Inventory. J Trauma Stress. (2005) 18:221–31. 10.1002/jts.20024
    1. Rozental A, Kottorp A, Forsström D, Månsson K, Boettcher J, Andersson G, et al. . The Negative Effects Questionnaire: psychometric properties of an instrument for assessing negative effects in psychological treatments. Behav Cogn Psychother. (2019) 47:559–72. 10.1017/S1352465819000018
    1. Pavuluri MN, Henry DB, Carbray JA, Sampson G, Naylor MW, Janicak PG. Open-label prospective trial of risperidone in combination with lithium or divalproex sodium in pediatric mania. J Affect Disord. (2004) 82:S103–S11. 10.1016/j.jad.2004.05.017
    1. Morin CM, Belleville G, Belanger L, Ivers H. The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep. (2011) 34:601–8. 10.1093/sleep/34.5.601
    1. Nordin M, Nordin S. Psychometric evaluation and normative data of the Swedish version of the 10-item perceived stress scale. Scand J Psychol. (2013) 54:502–7. 10.1111/sjop.12071
    1. Greco LA, Lambert W, Baer RA. Psychological inflexibility in childhood and adolescence: development and evaluation of the Avoidance and Fusion Questionnaire for Youth. Psychol Assess. (2008) 20:93–102. 10.1037/1040-3590.20.2.93
    1. Cederberg JT, Weineland S, Dahl J, Ljungman G. A preliminary validation of the Swedish short version of the Avoidance and Fusion Questionnaire for Youth (AFQ-Y8) for children and adolescents with cancer. J Context Behav Sci. (2018) 10:103–7. 10.1016/j.jcbs.2018.09.004
    1. Livheim F, Tengström A, Bond FW, Andersson G, Dahl J, Rosendahl I. Psychometric properties of the Avoidance and Fusion Questionnaire for Youth: a psychological measure of psychological inflexibility in youth. J Context Behav Sci. (2016) 5:103–10. 10.1016/j.jcbs.2016.04.001
    1. Bjureberg J, Ljotsson B, Tull MT, Hedman E, Sahlin H, Lundh LG, et al. . Development and validation of a brief version of the difficulties in emotion regulation scale: the DERS-16. J Psychopathol Behav Assess. (2016) 38:284–96. 10.1007/s10862-015-9514-x
    1. Gilbert PCF, Duarte C, Matos M, Kolts R, Stubbs J, Ceresatto L, et al. . The development of compassionate engagement and action scales for self and others. J Compassion Health Care. (2017) 4:4. 10.1186/s40639-017-0033-3
    1. Henje Blom ECRF, Gilbert P, Dennhag I. Psychometric validity of the Compassionate Engagement and Action Scale for Adolescents: a Swedish version. Scand J Child Adolesc Psychiatry Psychol. (2020) 8:70–80. 10.21307/sjcapp-2020-007
    1. Hagquist C. The psychometric properties of the self-reported SDQ - An analysis of Swedish data based on the Rasch model. Pers Individ Dif. (2007) 43:1289–301. 10.1016/j.paid.2007.03.022
    1. Lundh LG, Wangby-Lundh M, Bjarehed J. Self-reported emotional and behavioral problems in Swedish 14 to 15-year-old adolescents: a study with the self-report version of the Strengths and Difficulties Questionnaire. Scand J Psychol. (2008) 49:523–32. 10.1111/j.1467-9450.2008.00668.x
    1. Malmberg M, Rydell AM, Smedje H. Validity of the Swedish version of the Strengths and Difficulties Questionnaire (SDQ-Swe). Nord J Psychiatry. (2003) 57:357–63. 10.1080/08039480310002697
    1. Bergfors S, Astrom M, Burstrom K, Egmar AC. Measuring health-related quality of life with the EQ-5D-Y instrument in children and adolescents with asthma. Acta Paediatr. (2015) 104:167–73. 10.1111/apa.12863
    1. Burstrom K, Bartonek A, Brostrom EW, Sun S, Egmar AC. EQ-5D-Y as a health-related quality of life measure in children and adolescents with functional disability in Sweden: testing feasibility and validity. Acta Paediatr. (2014) 103:426–35. 10.1111/apa.12557
    1. Lundh LG, Karim J, Quilisch E. Deliberate self-harm in 15-year-old adolescents: a pilot study with a modified version of the Deliberate Self-Harm Inventory. Scand J Psychol. (2007) 48:33–41. 10.1111/j.1467-9450.2007.00567.x
    1. Bjarehed J, Lundh LG. Deliberate self-harm in 14-year-old adolescents: how frequent is it, and how is it associated with psychopathology, relationship variables, and styles of emotional regulation? Cogn Behav Ther. (2008) 37:26–37. 10.1080/16506070701778951
    1. Reynolds WM, Mazza JJ. Assessment of suicidal ideation in inner-city children and young adolescents: reliability and validity of the suicidal ideation questionnaire-JR. School Psych Rev. (1999) 28:17. 10.1080/02796015.1999.12085945
    1. Roseman L, Haijen E, Idialu-Ikato K, Kaelen M, Watts R, Carhart-Harris R. Emotional breakthrough and psychedelics: validation of the Emotional Breakthrough Inventory. J Psychopharmacol. (2019) 33:1076–87. 10.1177/0269881119855974
    1. Evans JP, Smith A, Gibbons C, Alonso J, Valderas JM. The National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS): a view from the UK. Patient Relat Outcome Meas. (2018) 9:345–52. 10.2147/PROM.S141378
    1. Schorre BE, Vandvik IH. Global assessment of psychosocial functioning in child and adolescent psychiatry. A review of three unidimensional scales (CGAS, GAF, GAPD). Eur Child Adolesc Psychiatry. (2004) 13:273–86. 10.1007/s00787-004-0390-2
    1. Koenig J, Kemp AH, Beauchaine TP, Thayer JF, Kaess M. Depression and resting state heart rate variability in children and adolescents - a systematic review and meta-analysis. Clin Psychol Rev. (2016) 46:136–50. 10.1016/j.cpr.2016.04.013
    1. Bot M, Milaneschi Y, Al-Shehri T, Amin N, Garmaeva S, Onderwater GLJ, et al. . Metabolomics profile in depression: a pooled analysis of 230 metabolic markers in 5283 cases with depression and 10,145 controls. Biol Psychiatry. (2020) 87:409–18. 10.1016/j.biopsych.2019.08.016
    1. Campbell A, Hemsley S. Outcome Rating Scale and Session Rating Scale in psychological practice: clinical utility of ultra-brief measures. Clin Psychologist. (2009) 13:1–9. 10.1080/13284200802676391
    1. Siddiqui O. MMRM versus MI in dealing with missing data–a comparison based on 25 NDA data sets. J Biopharm Stat. (2011) 21:423–36. 10.1080/10543401003777995
    1. Newgard CD, Lewis RJ. Missing data: how to best account for what is not known. JAMA. (2015) 314:940–1. 10.1001/jama.2015.10516
    1. Li P, Stuart EA, Allison DB. Multiple imputation: a flexible tool for handling missing data. JAMA. (2015) 314:1966–7. 10.1001/jama.2015.15281
    1. Altman DG, Bland JM. Absence of evidence is not evidence of absence. Bmj. (1995) 311:485. 10.1136/bmj.311.7003.485
    1. Althunian TA, de Boer A, Groenwold RHH, Klungel OH. Defining the noninferiority margin and analysing noninferiority: an overview. Br J Clin Pharmacol. (2017) 83:1636–42. 10.1111/bcp.13280
    1. Krysan DJ, Kemper AR. Claims of equivalence in randomized controlled trials of the treatment of bacterial meningitis in children. Pediatr Infect Dis J. (2002) 21:753–8. 10.1097/00006454-200208000-00011
    1. Committee for Proprietary Medicinal P . Points to consider on switching between superiority and non-inferiority. Br J Clin Pharmacol. (2001) 52:223–8. 10.1046/j.1365-2125.2001.01397-3.x
    1. EMEA . Points to consider on multiplicity in clinical trials. Biometric J. (2001) 43:1039–48. 10.1002/1521-4036(200112)43:8<1039::AID-BIMJ1039>;2-Y
    1. Ioannidis JP, Evans SJ, Gotzsche PC, O'Neill RT, Altman DG, Schulz K, et al. . Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med. (2004) 141:781–8. 10.7326/0003-4819-141-10-200411160-00009
    1. Detry MA, Ma Y. Analyzing repeated measurements using mixed models. JAMA. (2016) 315:407–8. 10.1001/jama.2015.19394
    1. Lee H, Herbert RD, McAuley JH. Mediation analysis. JAMA. (2019) 321:697–8. 10.1001/jama.2018.21973
    1. Faes MC, Reelick MF, Perry M, Olde Rikkert MG, Borm GF. Studies with group treatments required special power calculations, allocation methods, and statistical analyses. J Clin Epidemiol. (2012) 65:138–46. 10.1016/j.jclinepi.2011.05.007
    1. Jensen PS, Rubio-Stipec M, Canino G, Bird HR, Dulcan MK, Schwab-Stone ME, et al. . Parent and child contributions to diagnosis of mental disorder: are both informants always necessary? J Am Acad Child Adolesc Psychiatry. (1999) 38:1569–79. 10.1097/00004583-199912000-00019
    1. Smith SR. Making sense of multiple informants in child and adolescent psychopathology:a guide for clinicians. J Psychoeduc Assess. (2007) 25:139–49. 10.1177/0734282906296233
    1. McCarney R, Warner J, Iliffe S, van Haselen R, Griffin M, Fisher P. The Hawthorne Effect: a randomised, controlled trial. BMC Med Res Methodol. (2007) 7:30. 10.1186/1471-2288-7-30
    1. Lagerberg T, Molero Y, D'Onofrio BM, Fernández de la Cruz L, Lichtenstein P, Mataix-Cols D, et al. . Antidepressant prescription patterns and CNS polypharmacy with antidepressants among children, adolescents, and young adults: a population-based study in Sweden. Eur Child Adolesc Psychiatry. (2019) 28:1137–45. 10.1007/s00787-018-01269-2
    1. Horowitz MA, Taylor D. Tapering of SSRI treatment to mitigate withdrawal symptoms. Lancet Psychiatry. (2019) 6:538–46. 10.1016/S2215-0366(19)30032-X

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