The ReThink study: a 3-arm parallel randomized trial of cognitive bias modification, with and without adherence promotion, for adolescent anxiety disorder: trial design and protocol

Shelley Reetz, Gregory Clarke, Robin Weersing, Nader Amir, John Dickerson, Frances L Lynch, Michael C Leo, Andreea M Rawlings, Mi H Lee, Sara Gille, Shelley Reetz, Gregory Clarke, Robin Weersing, Nader Amir, John Dickerson, Frances L Lynch, Michael C Leo, Andreea M Rawlings, Mi H Lee, Sara Gille

Abstract

Background: Anxiety disorders are the most common mental health problem among youth, contribute to reduced quality of daily life, and are associated with high rates of comorbidity. However, treatment rates for anxiety are very low, causing a sizeable treatment gap. There is an immediate need to identify treatment interventions that are effective, affordable, and can be delivered easily to the youth population. Cognitive Bias Modification (CBM) is one potentially effective intervention that could reach youth on a large scale, especially when self-administered at home. Thus, we aim to assess the benefit of CBM to treat youth anxiety. Further, we aim to test whether adding an adherence promotion (AP) component to the CBM intervention can improve outcomes, and whether CBM delivered both with and without the AP component is cost effective.

Methods: This is a 12-month randomized controlled trial (RCT) conducted within an existing healthcare system. Potentially eligible youth (ages 12 to 17) will be identified by reviewing the electronic health record (EHR) for clinical anxiety diagnoses, which are then confirmed via research interview. We aim to enroll 498 participants and randomize them 1:1:1 to one of three arms: Arm 1 is a Low-Ratio version of the CBM program (nearly identical to the other CBM versions, but minimally effective); Arm 2 is a High-Ratio "active" CBM program; and Arm 3 is the High-Ratio CBM program with an added AP component. Participants will complete assessments at baseline, 1-, 3-, 6- and 12-months post-baseline. Youth in all three arms will self-administer the CBM program at home and will be asked to complete twelve intervention sessions over a four-week period. Arm 3 participants (High-Ratio CBM + AP) will also receive up to four telephone calls from phone coaches during the intervention period to provide technical assistance, encouragement, and motivational enhancement to increase adherence. The primary clinical outcome will be anxiety remission at 6-month follow-up.

Discussion: This study protocol describes the method and design for an RCT to test whether self-administered CBM both with and without adherence promotion can be an effective at-home treatment for anxious youth.

Trial registration: ClinicalTrials.gov : NCT02156531, First Posted June 5, 2014.

Keywords: Adolescent; Anxiety disorder; Cognitive bias modification; Randomized controlled trial.

Conflict of interest statement

Dr. Amir was formerly a part owner of Cognitive Retraining Technologies, LLC (“CRT”), a company that marketed anxiety relief products. Dr. Amir’s ownership interest in CRT was extinguished on January 29, 2016, when CRT was acquired by another entity. Dr. Amir has an interest in royalty income generated by the marketing of anxiety relief products by this entity.

Figures

Fig. 1
Fig. 1
Participant Flow Diagram
Fig. 2
Fig. 2
Cognitive Bias Modification (CBM) program screenshots

References

    1. Merikangas KR, He JP, Burstein M, Swanson SA, Avenevoli S, Cui L, et al. Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication--Adolescent Supplement (NCS-A) J Am Acad Child Adolesc Psychiatry. 2010;49(10):980–989. doi: 10.1016/j.jaac.2010.05.017.
    1. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617–627. doi: 10.1001/archpsyc.62.6.617.
    1. Marciniak MD, Lage MJ, Dunayevich E, Russell JM, Bowman L, Landbloom RP, et al. The cost of treating anxiety: the medical and demographic correlates that impact total medical costs. Depress Anxiety. 2005;21(4):178–184. doi: 10.1002/da.20074.
    1. Revicki DA, Travers K, Wyrwich KW, Svedsater H, Locklear J, Mattera MS, et al. Humanistic and economic burden of generalized anxiety disorder in North America and Europe. J Affect Disord. 2012;140(2):103–112. doi: 10.1016/j.jad.2011.11.014.
    1. Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci. 2015;17(3):327.
    1. Harvard Medical School. National Comorbidity Survey (NCS) Data Table 2: 12-month prevalence DSM-IV/WMH-CIDI disorders by sex and cohort. 2007. . 2019.
    1. Harvard Medical School. National Comorbidity Survey (NCS) Data Table 1: Lifetime prevalence DSM-IV/WMH-CIDI disorders by sex and cohort. 2007. . 2019.
    1. Merikangas KR, He JP, Brody D, Fisher PW, Bourdon K, Koretz DS. Prevalence and treatment of mental disorders among US children in the 2001-2004 NHANES. Pediatrics. 2010;125(1):75–81. doi: 10.1542/peds.2008-2598.
    1. Ringle VA, Read KL, Edmunds JM, Brodman DM, Kendall PC, Barg F, et al. Barriers to and facilitators in the implementation of cognitive-behavioral therapy for youth anxiety in the community. Psychiatr Serv. 2015;66(9):938–945. doi: 10.1176/appi.ps.201400134.
    1. Hallerman Price J. Adherence Barriers to Antidepressants among an Urban Female Latino Population 2013. . 2019.
    1. Mathews A, MacLeod C. Cognitive vulnerability to emotional disorders. Annu Rev Clin Psychol. 2005;1:167–195. doi: 10.1146/annurev.clinpsy.1.102803.143916.
    1. MacLeod Colin, Grafton Ben, Notebaert Lies. Anxiety-Linked Attentional Bias: Is It Reliable? Annual Review of Clinical Psychology. 2019;15(1):529–554. doi: 10.1146/annurev-clinpsy-050718-095505.
    1. Bar-Haim Y, Lamy D, Pergamin L, Bakermans-Kranenburg MJ, Van Ijzendoorn MH. Threat-related attentional bias in anxious and nonanxious individuals: a meta-analytic study. Psychol Bull. 2007;133(1):1. doi: 10.1037/0033-2909.133.1.1.
    1. Clarke PJ, Notebaert L, MacLeod C. Absence of evidence or evidence of absence: reflecting on therapeutic implementations of attentional bias modification. BMC Psychiatry. 2014;14:8. doi: 10.1186/1471-244x-14-8.
    1. Sportel BE, de Hullu E, de Jong PJ, Nauta MH. Cognitive bias modification versus CBT in reducing adolescent social anxiety: a randomized controlled trial. PLoS One. 2013;8(5):e64355. doi: 10.1371/journal.pone.0064355.
    1. Taylor C, Aupperle R, Flagan T. al. e. Attentional training boosts top-down neural activation underlying emotion processing in anxious subjects. Biol Psychiatry. In Press.
    1. Koster EH, Fox E, MacLeod C. Introduction to the special section on cognitive bias modification in emotional disorders. J Abnorm Psychol. 2009;118(1):1–4. doi: 10.1037/a0014379.
    1. Amir N, Beard C, Burns M, Bomyea J. Attention modification program in individuals with generalized anxiety disorder. J Abnorm Psychol. 2009;118(1):28–33. doi: 10.1037/a0012589.
    1. Schmidt NB, Richey JA, Buckner JD, Timpano KR. Attention training for generalized social anxiety disorder. J Abnorm Psychol. 2009;118(1):5–14. doi: 10.1037/a0013643.
    1. Amir N, Beard C, Taylor CT, Klumpp H, Elias J, Burns M, et al. Attention training in individuals with generalized social phobia: a randomized controlled trial. J Consult Clin Psychol. 2009;77(5):961–973. doi: 10.1037/a0016685.
    1. Heeren A, Reese HE, McNally RJ, Philippot P. Attention training toward and away from threat in social phobia: effects on subjective, behavioral, and physiological measures of anxiety. Behav Res Ther. 2012;50(1):30–39. doi: 10.1016/j.brat.2011.10.005.
    1. Carlbring P, Apelstrand M, Sehlin H, Amir N, Rousseau A, Hofmann SG, et al. Internet-delivered attention bias modification training in individuals with social anxiety disorder--a double blind randomized controlled trial. BMC Psychiatry. 2012;12:66. doi: 10.1186/1471-244x-12-66.
    1. Riemann BC, Kuckertz JM, Rozenman M, Weersing VR, Amir N. Augmentation of youth cognitive behavioral and pharmacological interventions with attention modification: a preliminary investigation. Depress Anxiety. 2013;30(9):822–828. doi: 10.1002/da.22127.
    1. Rozenman M, Weersing VR, Amir N. A case series of attention modification in clinically anxious youths. Behav Res Ther. 2011;49(5):324–330. doi: 10.1016/j.brat.2011.02.007.
    1. Eldar S, Apter A, Lotan D, Edgar KP, Naim R, Fox NA, et al. Attention bias modification treatment for pediatric anxiety disorders: a randomized controlled trial. Am J Psychiatry. 2012;169(2):213–220. doi: 10.1176/appi.ajp.2011.11060886.
    1. Ioannidis JP. Contradicted and initially stronger effects in highly cited clinical research. Jama. 2005;294(2):218–228. doi: 10.1001/jama.294.2.218.
    1. Neubauer K, von Auer M, Murray E, Petermann F, Helbig-Lang S, Gerlach AL. Internet-delivered attention modification training as a treatment for social phobia: a randomized controlled trial. Behav Res Ther. 2013;51(2):87–97. doi: 10.1016/j.brat.2012.10.006.
    1. Beard C, Sawyer AT, Hofmann SG. Efficacy of attention bias modification using threat and appetitive stimuli: a meta-analytic review. Behav Ther. 2012;43(4):724–740. doi: 10.1016/j.beth.2012.01.002.
    1. Krebs G, Hirsch CR, Mathews A. The effect of attention modification with explicit vs. minimal instructions on worry. Behav Res Ther. 2010;48(3):251–256. doi: 10.1016/j.brat.2009.10.009.
    1. Digdon NL, Howell AJ. College students who have an eveningness preference report lower self-control and greater procrastination. Chronobiol Int. 2008;25(6):1029–1046. doi: 10.1080/07420520802553671.
    1. Hettema J, Steele J, Miller WR. Motivational interviewing. Annu Rev Clin Psychol. 2005;1:91–111. doi: 10.1146/annurev.clinpsy.1.102803.143833.
    1. Miller WR, Rollnick S. Motivational interviewing: preparing people for change. Second edition ed. New York: Guilford Press; 2012.
    1. Amir N, Taylor CT, Donohue MC. Predictors of response to an attention modification program in generalized social phobia. J Consult Clin Psychol. 2011;79(4):533–541. doi: 10.1037/a0023808.
    1. Silverman WK, Saavedra LM, Pina AA. Test-retest reliability of anxiety symptoms and diagnoses with the anxiety disorders interview schedule for DSM-IV: child and parent versions. J Am Acad Child Adolesc Psychiatry. 2001;40(8):937–944. doi: 10.1097/00004583-200108000-00016.
    1. Silverman WK, Nelles WB. The anxiety disorders interview schedule for children. J Am Acad Child Adolesc Psychiatry. 1988;27(6):772–778. doi: 10.1097/00004583-198811000-00019.
    1. RUPP The pediatric anxiety rating scale (PARS): development and psychometric properties. J Am Acad Child Adolesc Psychiatry. 2002;41(9):1061–1069. doi: 10.1097/00004583-200209000-00006.
    1. Compton SN, Walkup JT, Albano AM, Piacentini JC, Birmaher B, Sherrill JT, et al. Child/adolescent anxiety multimodal study (CAMS): rationale, design, and methods. Child Adolesc Psychiatry Ment Health. 2010;4:1. doi: 10.1186/1753-2000-4-1.
    1. Walkup JT, Albano AM, Piacentini J, Birmaher B, Compton SN, Sherrill JT, et al. Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. N Engl J Med. 2008;359(26):2753–2766. doi: 10.1056/NEJMoa0804633.
    1. Birmaher B, Brent DA, Chiappetta L, Bridge J, Monga S, Baugher M. Psychometric properties of the screen for child anxiety related emotional disorders (SCARED): a replication study. J Am Acad Child Adolesc Psychiatry. 1999;38(10):1230–1236. doi: 10.1097/00004583-199910000-00011.
    1. Whiteside SP, Gryczkowski M, Ale CM, Brown-Jacobsen AM, McCarthy DM. Development of child- and parent-report measures of behavioral avoidance related to childhood anxiety disorders. Behav Ther. 2013;44(2):325–337. doi: 10.1016/j.beth.2013.02.006.
    1. Richardson LP, McCauley E, Grossman DC, McCarty CA, Richards J, Russo JE, et al. Evaluation of the patient health Questionnaire-9 item for detecting major depression among adolescents. Pediatrics. 2010;126(6):1117–1123. doi: 10.1542/peds.2010-0852.
    1. Guy W. Clinical global improvement scale. Rockville, MD: National Institute of Mental Health; 1976.
    1. Shaffer D, Gould MS, Brasic J, Ambrosini P, Fisher P, Bird H, et al. A children's global assessment scale (CGAS) Arch Gen Psychiatry. 1983;40(11):1228–1231. doi: 10.1001/archpsyc.1983.01790100074010.
    1. Ascher BHZ, Farmer EM, Burns BJ, Angold A. The child and adolescent services assessment (CASA) description and psychometrics. J Emot Behav Disord. 1996;4(1):12–20. doi: 10.1177/106342669600400102.
    1. EuroQol G. EuroQol--a new facility for the measurement of health-related quality of life. Health Policy. 1990;16(3):199–208. doi: 10.1016/0168-8510(90)90421-9.
    1. Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol group. Ann Med. 2001;33(5):337–343. doi: 10.3109/07853890109002087.
    1. Bereza BG, Machado M, Einarson TR. Systematic review and quality assessment of economic evaluations and quality-of-life studies related to generalized anxiety disorder. Clin Ther. 2009;31(6):1279–1308. doi: 10.1016/j.clinthera.2009.06.004.
    1. Saarni SI, Suvisaari J, Sintonen H, Pirkola S, Koskinen S, Aromaa A, et al. Impact of psychiatric disorders on health-related quality of life: general population survey. Br J Psychiatry. 2007;190:326–332. doi: 10.1192/bjp.bp.106.025106.
    1. Whynes DK. Responsiveness of the EQ-5D to HADS-identified anxiety and depression. J Eval Clin Pract. 2009;15(5):820–825. doi: 10.1111/j.1365-2753.2008.01102.x.
    1. Willems DC, Joore MA, Nieman FH, Severens JL, Wouters EF, Hendriks JJ. Using EQ-5D in children with asthma, rheumatic disorders, diabetes, and speech/language and/or hearing disorders. Int J Technol Assess Health Care. 2009;25(3):391–399. doi: 10.1017/s0266462309990171.
    1. Julian LJ. Measures of anxiety: state-trait anxiety inventory (STAI), Beck anxiety inventory (BAI), and hospital anxiety and depression scale-anxiety (HADS-A) Arthritis Care Res (Hoboken) 2011;63(Suppl 11):S467–S472. doi: 10.1002/acr.20561.
    1. Carskadon MA, Acebo C. A self-administered rating scale for pubertal development. J Adolesc Health. 1993;14(3):190–195. doi: 10.1016/1054-139X(93)90004-9.
    1. Brooks-Gunn J, Warren MP, Rosso J, Gargiulo J. Validity of self-report measures of girls' pubertal status. Child Dev. 1987.
    1. Petersen AC, Crockett L, Richards M, Boxer A. A self-report measure of pubertal status: reliability, validity, and initial norms. J Youth Adolescence. 1988;17(2):117–133. doi: 10.1007/BF01537962.
    1. Bastien CH, Vallieres A, Morin CM. Validation of the insomnia severity index as an outcome measure for insomnia research. Sleep Med. 2001;2(4):297–307. doi: 10.1016/S1389-9457(00)00065-4.
    1. Morin C. M. Insomnia: psychological assessment and management: Guilford press; 1993.
    1. Attkisson CC, Greenfield T. The client satisfaction questionnaire (CSQ) scales. Outcome assessment in clinical practice. Baltimore, MD: Williams & Wilkins; 1995. pp. 2–10.
    1. Mander J, Wittorf A, Teufel M, Schlarb A, Hautzinger M, Zipfel S, et al. Patients with depression, somatoform disorders, and eating disorders on the stages of change: validation of a short version of the URICA. Psychotherapy (Chic) 2012;49(4):519–527. doi: 10.1037/a0029563.
    1. Dunn G, Bentall R. Modelling treatment-effect heterogeneity in randomized controlled trials of complex interventions (psychological treatments) Stat Med. 2007;26(26):4719–4745. doi: 10.1002/sim.2891.
    1. Wells KB, Tang L, Carlson GA, Asarnow JR. Treatment of youth depression in primary care under usual practice conditions: observational findings from youth Partners in Care. J Child Adolesc Psychopharmacol. 2012;22(1):80–90. doi: 10.1089/cap.2011.0074.
    1. Eldar S, Ricon T, Bar-Haim Y. Plasticity in attention: implications for stress response in children. Behav Res Ther. 2008;46(4):450–461. doi: 10.1016/j.brat.2008.01.012.
    1. Bar-Haim Y. Research review: attention bias modification (ABM): a novel treatment for anxiety disorders. J Child Psychol Psychiatry. 2010;51(8):859–870. doi: 10.1111/j.1469-7610.2010.02251.x.
    1. Kuckertz JM, Gildebrant E, Liliequist B, Karlström P, Väppling C, Bodlund O, et al. Moderation and mediation of the effect of attention training in social anxiety disorder. Behav Res Ther. 2014;53:30–40. doi: 10.1016/j.brat.2013.12.003.
    1. Raudenbush S. W., Bryk A. S. Hierarchical linear models: applications and data analysis methods: sage; 2002.
    1. Snijders TBR. Multilevel analysis: an introduction to basic and advanced multilevel modeling. Thousand Oaks, CA: Sage; 1999.
    1. Hox J. J., Moerbeek M., Van de Schoot R. Multilevel analysis: techniques and applications: Routledge; 2017.
    1. Royston P, Altman DG. Regression using fractional polynomials of continuous covariates: parsimonious parametric modelling. J R Stat Soc: Ser C: Appl Stat. 1994;43(3):429–453.
    1. Royston P, Sauerbrei W. Multivariable model-building: a pragmatic approach to regression anaylsis based on fractional polynomials for modelling continuous variables: John Wiley & Sons. 2008.
    1. Hayes AF. Beyond baron and Kenny: statistical mediation analysis in the new millennium. Commun Monogr. 2009;76(4):408–420. doi: 10.1080/03637750903310360.
    1. MacKinnon D. Introduction to statistical mediation analysis: Routledge; 2012.
    1. MacKinnon DP, Lockwood CM, Hoffman JM, West SG, Sheets V. A comparison of methods to test mediation and other intervening variable effects. Psychol Methods. 2002;7(1):83. doi: 10.1037/1082-989X.7.1.83.
    1. Mackinnon DP, Lockwood CM, Williams J. Confidence limits for the indirect effect: distribution of the product and resampling methods. Multivariate Behav Res. 2004;39(1):99. doi: 10.1207/s15327906mbr3901_4.
    1. Enders C. K. Applied missing data analysis: Guilford press; 2010.
    1. Schafer JL, Graham JW. Missing data: our view of the state of the art. Psychol Methods. 2002;7(2):147–177. doi: 10.1037/1082-989X.7.2.147.
    1. Allison P. D. Missing data: sage thousand oaks, CA; 2010.
    1. Chinn S. A simple method for converting an odds ratio to effect size for use in meta-analysis. Stat Med. 2000;19(22):3127–3131. doi: 10.1002/1097-0258(20001130)19:22<3127::AID-SIM784>;2-M.
    1. Hintze J. PASS 2008. LLC. Kaysville, Utah, USA: NCSS; 2008.
    1. Weinstein M. C., Russell L. B., Gold M. R., Siegel J. E. Cost-effectiveness in health and medicine: Oxford university press; 1996.
    1. Lynch FL, Striegel-Moore RH, Dickerson JF, Perrin N, Debar L, Wilson GT, et al. Cost-effectiveness of guided self-help treatment for recurrent binge eating. J Consult Clin Psychol. 2010;78(3):322–333. doi: 10.1037/a0018982.
    1. Lynch FL, Dickerson JF, Clarke G, Vitiello B, Porta G, Wagner KD, et al. Incremental cost-effectiveness of combined therapy vs medication only for youth with selective serotonin reuptake inhibitor-resistant depression: treatment of SSRI-resistant depression in adolescents trial findings. Arch Gen Psychiatry. 2011;68(3):253–262. doi: 10.1001/archgenpsychiatry.2011.9.
    1. Konig HH, Born A, Heider D, Matschinger H, Heinrich S, Riedel-Heller SG, et al. Cost-effectiveness of a primary care model for anxiety disorders. Br J Psychiatry. 2009;195(4):308–317. doi: 10.1192/bjp.bp.108.058032.
    1. Hoek W, Schuurmans J, Koot HM, Cuijpers P. Prevention of depression and anxiety in adolescents: a randomized controlled trial testing the efficacy and mechanisms of internet-based self-help problem-solving therapy. Trials. 2009;10:93. doi: 10.1186/1745-6215-10-93.
    1. Bodden DH, Dirksen CD, Bogels SM, Nauta MH, De Haan E, Ringrose J, et al. Costs and cost-effectiveness of family CBT versus individual CBT in clinically anxious children. Clin Child Psychol Psychiatry. 2008;13(4):543–564. doi: 10.1177/1359104508090602.
    1. Chisholm D, Healey A, Knapp M. QALYs and mental health care. Soc Psychiatry Psychiatr Epidemiol. 1997;32(2):68–75. doi: 10.1007/BF00788923.
    1. Knapp M., Mangalore R. "The trouble with QALYs...". Epidemiol Psichiatr Soc 2007; 16(4):289–293.
    1. Brazier J. Measuring and valuing mental health for use in economic evaluation. J Health Serv Res Policy. 2008;13(Suppl 3):70–75. doi: 10.1258/jhsrp.2008.008015.
    1. Iskedjian M, Walker JH, Bereza BG, Le Melledo JM, Einarson TR. Cost-effectiveness of escitalopram for generalized anxiety disorder in Canada. Curr Med Res Opin. 2008;24(5):1539–1548. doi: 10.1185/030079908x297277.
    1. McCrone P, Knapp M, Proudfoot J, Ryden C, Cavanagh K, Shapiro DA, et al. Cost-effectiveness of computerised cognitive-behavioural therapy for anxiety and depression in primary care: randomised controlled trial. Br J Psychiatry. 2004;185:55–62. doi: 10.1192/bjp.185.1.55.
    1. Simon E, Dirksen C, Bogels S, Bodden D. Cost-effectiveness of child-focused and parent-focused interventions in a child anxiety prevention program. J Anxiety Disord. 2012;26(2):287–296. doi: 10.1016/j.janxdis.2011.12.008.
    1. Katon WJ, Roy-Byrne P, Russo J, Cowley D. Cost-effectiveness and cost offset of a collaborative care intervention for primary care patients with panic disorder. Arch Gen Psychiatry. 2002;59(12):1098–1104. doi: 10.1001/archpsyc.59.12.1098.
    1. Katon W, Russo J, Sherbourne C, Stein MB, Craske M, Fan MY, et al. Incremental cost-effectiveness of a collaborative care intervention for panic disorder. Psychol Med. 2006;36(3):353–363. doi: 10.1017/s0033291705006896.
    1. Zimovetz EA, Wolowacz SE, Classi PM, Birt J. Methodologies used in cost-effectiveness models for evaluating treatments in major depressive disorder: a systematic review. Cost Eff Resour Alloc. 2012;10(1):1. doi: 10.1186/1478-7547-10-1.
    1. Joesch JM, Sherbourne CD, Sullivan G, Stein MB, Craske MG, Roy-Byrne P. Incremental benefits and cost of coordinated anxiety learning and management for anxiety treatment in primary care. Psychol Med. 2012;42(9):1937–1948. doi: 10.1017/s0033291711002893.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner