Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents: protocol for a randomised clinical trial (the TECTO trial)

Anne Katrine Pagsberg, Camilla Uhre, Valdemar Uhre, Linea Pretzmann, Sofie Heidenheim Christensen, Christine Thoustrup, Iben Clemmesen, Amanda Aaen Gudmandsen, Nicoline Løcke Jepsen Korsbjerg, Anna-Rosa Cecilie Mora-Jensen, Melanie Ritter, Emilie D Thorsen, Klara Sofie Vangstrup Halberg, Birgitte Bugge, Nina Staal, Helga Kristensen Ingstrup, Birgitte Borgbjerg Moltke, Anne Murphy Kloster, Pernille Juul Zoega, Marie Sommer Mikkelsen, Gitte Sommer Harboe, Katrin Frimann Larsen, Line Katrine Harder Clemmensen, Jane Lindschou, Janus Christian Jakobsen, Janus Engstrøm, Christian Gluud, Hartwig Roman Siebner, Per Hove Thomsen, Katja Hybel, Frank Verhulst, Pia Jeppesen, Jens Richardt Møllegaard Jepsen, Signe Vangkilde, Markus Harboe Olsen, Julie Hagstrøm, Nicole Nadine Lønfeldt, Kerstin Jessica Plessen, Anne Katrine Pagsberg, Camilla Uhre, Valdemar Uhre, Linea Pretzmann, Sofie Heidenheim Christensen, Christine Thoustrup, Iben Clemmesen, Amanda Aaen Gudmandsen, Nicoline Løcke Jepsen Korsbjerg, Anna-Rosa Cecilie Mora-Jensen, Melanie Ritter, Emilie D Thorsen, Klara Sofie Vangstrup Halberg, Birgitte Bugge, Nina Staal, Helga Kristensen Ingstrup, Birgitte Borgbjerg Moltke, Anne Murphy Kloster, Pernille Juul Zoega, Marie Sommer Mikkelsen, Gitte Sommer Harboe, Katrin Frimann Larsen, Line Katrine Harder Clemmensen, Jane Lindschou, Janus Christian Jakobsen, Janus Engstrøm, Christian Gluud, Hartwig Roman Siebner, Per Hove Thomsen, Katja Hybel, Frank Verhulst, Pia Jeppesen, Jens Richardt Møllegaard Jepsen, Signe Vangkilde, Markus Harboe Olsen, Julie Hagstrøm, Nicole Nadine Lønfeldt, Kerstin Jessica Plessen

Abstract

Background: Cognitive behavioural therapy (CBT) is the recommended first-line treatment for children and adolescents with obsessive-compulsive disorder (OCD), but evidence concerning treatment-specific benefits and harms compared with other interventions is limited. Furthermore, high risk-of-bias in most trials prevent firm conclusions regarding the efficacy of CBT. We investigate the benefits and harms of family-based CBT (FCBT) versus family-based psychoeducation and relaxation training (FPRT) in youth with OCD in a trial designed to reduce risk-of-bias.

Methods: This is an investigator-initiated, independently funded, single-centre, parallel group superiority randomised clinical trial (RCT). Outcome assessors, data managers, statisticians, and conclusion drawers are blinded. From child and adolescent mental health services we include patients aged 8-17 years with a primary OCD diagnosis and an entry score of ≥16 on the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). We exclude patients with comorbid illness contraindicating trial participation; intelligence quotient < 70; or treatment with CBT, PRT, antidepressant or antipsychotic medication within the last 6 months prior to trial entry. Participants are randomised 1:1 to the experimental intervention (FCBT) versus the control intervention (FPRT) each consisting of 14 75-min sessions. All therapists deliver both interventions. Follow-up assessments occur in week 4, 8 and 16 (end-of-treatment). The primary outcome is OCD symptom severity assessed with CY-BOCS at end-of-trial. Secondary outcomes are quality-of-life and adverse events. Based on sample size estimation, a minimum of 128 participants (64 in each intervention group) are included.

Discussion: In our trial design we aim to reduce risk-of-bias, enhance generalisability, and broaden the outcome measures by: 1) conducting an investigator-initiated, independently funded RCT; 2) blinding investigators; 3) investigating a representative sample of OCD patients; 3) using an active control intervention (FPRT) to tease apart general and specific therapy effects; 4) using equal dosing of interventions and therapist supervision in both intervention groups; 5) having therapists perform both interventions decided by randomisation; 6) rating fidelity of both interventions; 7) assessing a broad range of benefits and harms with repeated measures. The primary study limitations are the risk of missing data and the inability to blind participants and therapists to the intervention.

Trial registration: ClinicalTrials.gov : NCT03595098, registered July 23, 2018.

Keywords: Adolescents; Children; Cognitive behavioural therapy; Obsessive-compulsive disorder; Psycho-education and relaxation training; Randomised clinical trial; Treatment effects; Youth.

Conflict of interest statement

Hartwig R. Siebner has received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark, Lophora, Denmark, and Lundbeck AS, Denmark, and as editor-in-chief (Neuroimage Clinical) and senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany and from Gyldendal Publishers, Copenhagen, Denmark.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
TECTO flow diagram

References

    1. Heyman I, et al. Prevalence of obsessive-compulsive disorder in the British nationwide survey of child mental health. International Rev Psychiatry. 2003;15(1–2):178–184.
    1. Piacentini J, et al. Functional impairment in children and adolescents with obsessive-compulsive disorder. J Child Adolesc Psychopharmacol. 2003;13(Suppl 1):S61–S69.
    1. Dalsgaard S, et al. Incidence rates and cumulative incidences of the full spectrum of diagnosed mental disorders in childhood and adolescence. JAMA Psychiatry. 2020;77(2):155–164.
    1. WHO, The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. 1992: Geneva: World Health Organization.
    1. Micali N, et al. Long-term outcomes of obsessive–compulsive disorder: follow-up of 142 children and adolescents. Br J Psychiatry. 2010;197(2):128–134.
    1. Eisen JL, et al. A 2-year prospective follow-up study of the course of obsessive-compulsive disorder. J Clin Psychiatry. 2010;71(8):1,478–11039.
    1. NICE. Obsessive-compulsive disorder and body dysmorphic disorder: treatment. National Institute for Health and Clinical Excellence. 2005; Available from: .
    1. Sundhedsstyrelsen. National klinisk retningslinje for behandling af obsessiv-kompulsiv tilstand (OCD). 2016; Available from: .
    1. Geller DA, March J. Practice parameter for the assessment and treatment of children and adolescents with obsessive-compulsive disorder. Focus. 2012;10(3):360–373.
    1. Uhre CF, et al. Systematic review and meta-analysis: cognitive-behavioral therapy for obsessive-compulsive disorder in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2020;59(1):64–77.
    1. Freeman JB, et al. Early childhood OCD: preliminary findings from a family-based cognitive-behavioral approach. J Am Acad Child Adolesc Psychiatry. 2008;47(5):593–602.
    1. Freeman J, et al. Family-based treatment of early childhood obsessive-compulsive disorder: the pediatric obsessive-compulsive disorder treatment study for young children (POTS Jr)--a randomized clinical trial. JAMA Psychiatry. 2014;71(6):689–698.
    1. Piacentini J, et al. Controlled comparison of family cognitive behavioral therapy and psychoeducation/relaxation training for child obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 2011;50(11):1149–1161.
    1. Uhre VF, et al. Dr. Uhre et al. reply. J Am Acad Child Adolesc Psychiatry. 2020;59(7):787–791.
    1. Fernandez E, et al. Meta-analysis of dropout from cognitive behavioral therapy: magnitude, timing, and moderators. J Consult Clin Psychol. 2015;83(6):1108–1122.
    1. Jonsson U, et al. Reporting of harms in randomized controlled trials of psychological interventions for mental and behavioral disorders: a review of current practice. Contemporary Clinical Trials. 2014;38(1):1–8.
    1. Jonsson U, et al. Adverse effects of psychological therapy: an exploratory study of practitioners’ experiences from child and adolescent psychiatry. Clinical child psychology and psychiatry. 2016;21(3):432–446.
    1. Crawford MJ, et al. Patient experience of negative effects of psychological treatment: results of a national survey. Br J Psychiatry. 2016;208(3):260–265.
    1. Chan A-W, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–207.
    1. Axelsen MC, et al. A multimodal modeling approach to schizophrenia. 2018.
    1. Kaufman J, et al. Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36(7):980–988.
    1. Scahill L, et al. Children's Yale-Brown obsessive compulsive scale: reliability and validity. J Am Acad Child Adolesc Psychiatry. 1997;36(6):844–852.
    1. Thomsen PH, et al. The Nordic long-term OCD treatment study (NordLOTS): rationale, design, and methods. Child Adolesc Psychiatry Ment Health. 2013;7(1):41.
    1. Wechsler D. WISC-V: Technical and interpretive manual. NCS Pearson, Incorporated; 2014.
    1. Wechsler D, Coalson DL, Raiford SE. WAIS-IV: Wechsler adult intelligence scale. San Antonio: Pearson; 2008.
    1. Constantino JN, Gruber CP, Social responsiveness scale (SRS). Western psychological services Los Angeles. CA. 2007.
    1. Piacentini J, Langley AK. Cognitive-behavioral therapy for children who have obsessive-compulsive disorder. J Clin Psychol. 2004;60(11):1181–1194.
    1. Lebowitz ER, Panza KE, Bloch MH. Family accommodation in obsessive-compulsive and anxiety disorders: a five-year update. Expert Rev Neurother. 2016;16(1):45–53.
    1. Manassis K. In: Child–parent relations: Attachment and anxiety disorders. Silverman WK, Treffers PDA, editors. Cambridge University Press; 2001. pp. 255–272.
    1. Silverman WK, Ollendick TH. Evidence-based assessment of anxiety and its disorders in children and adolescents. J Clin Child Adolesc Psychol. 2005;34(3):380–411.
    1. Rocha NB, Queiros C. Metacognitive and social cognition training (MSCT) in schizophrenia: a preliminary efficacy study. Schizophr Res. 2013;150(1):64–68.
    1. Ravens-Sieberer U, et al. KIDSCREEN-52 quality-of-life measure for children and adolescents. Expert Rev Pharmacoeconomics Outcomes Res. 2005;5(3):353–364.
    1. Piacentini J, et al. Functional impairment in childhood OCD : Development and psychometrics properties of the Child Obsessive-Compulsive Impact Scale--Revised (COIS--R). J Clin Child Adolescent Psychology. 2007;36(4).
    1. Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont) 2007;4(7):28–37.
    1. Shaffer D, et al. A children's global assessment scale (CGAS) Arch Gen Psychiatry. 1983;40(11):1228–1231.
    1. Park LS, et al. The Toronto Obsessive-Compulsive Scale: psychometrics of a dimensional measure of obsessive-compulsive traits. J Am Academy Child Adolescent Psychiatr. 2016;55(4):310–318.
    1. Calvocoressi L, et al. Family accommodation of obsessive-compulsive symptoms: instrument development and assessment of family behavior. J Nerv Ment Dis. 1999;187(10):636–642.
    1. Berry JO, Jones WH. The parental stress scale: initial psychometric evidence. J Soc Pers Relat. 1995;12(3):463–472.
    1. Boyd CP, et al. The family environment scale: reliability and normative data for an adolescent sample. Fam Process. 1997;36(4):369–373.
    1. Shirk SR, Saiz CC. Clinical, empirical, and developmental perspectives on the therapeutic relationship in child psychotherapy. Dev Psychopathol. 1992;4(4):713–728.
    1. Keeley ML, et al. The therapeutic alliance in the cognitive behavioral treatment of pediatric obsessive-compulsive disorder. J Anxiety Disord. 2011;25(7):855–863.
    1. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use (ICD) adopts consolidated guideline on good clinical practice in the conduct of clinical trials on medicinal products for human use. International Digest of Health Legislation, 1997. 48(2): p. 231–234.
    1. Thomsen PH, Weidle B. Behandling af børn og unge med OCD. En praksismanual. 2015. Copenhagen: Hans Reitzels Forlag.
    1. March J, Mulle K. OCD in children and adolescents: a cognitive-behavioral treatment manual. 1998. New York: Guilford Press.
    1. Torp NC, et al. Effectiveness of cognitive behavior treatment for pediatric obsessive-compulsive disorder: acute outcomes from the Nordic long-term OCD treatment study (NordLOTS) Behav Res Ther. 2015;64:15–23.
    1. Cautela J, Groden J. Relaxation: a comprehensive manual for adults, children, and children with special needs. Champagne: Research Press; 1978.
    1. Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care. 2003;41(5):582–592.
    1. Jakobsen JC, et al. When and how should multiple imputation be used for handling missing data in randomised clinical trials–a practical guide with flowcharts. BMC Med Res Methodol. 2017;17(1):1–10.
    1. Jakobsen J, et al. Count data analysis in randomised clinical trials. J Biomet Biostat. 2015;6(1):227.
    1. Foa EB, McLean CP. The efficacy of exposure therapy for anxiety-related disorders and its underlying mechanisms: the case of OCD and PTSD. Annu Rev Clin Psychol. 2015.
    1. Foa EB, et al. Deliberate exposure and blocking of obsessive-compulsive rituals: immediate and long-term effects. Behav Ther. 1984;15(5):450–472.
    1. Adams TG, Lohr JM. Disgust mediates the relation between attentional shifting and contamination aversion. J Behav Ther Exp Psychiatry. 2012;43(4):975–980.
    1. Storch EA, et al. Frequency and correlates of suicidal ideation in pediatric obsessive–compulsive disorder. Child Psychiatry Hum Dev. 2015;46(1):75–83.
    1. Benatti B, et al. Prevalence and correlates of current suicide risk in an international sample of OCD adults: a report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network and obsessive compulsive and related disorders network (OCRN) of the European College of Neuropsychopharmacology. J Psychiatr Res. 2021.
    1. Kamath P, Reddy YJ, Kandavel T. Suicidal behavior in obsessive-compulsive disorder. J Clin Psychiatry. 2007;68(11):0–0.
    1. Torres, A.R., et al., Suicidality in obsessive-compulsive disorder: prevalence and relation to symptom dimensions and comorbid conditions. J Clin Psychiatry, 2011. 72(1): p. 0–0.

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