Schema therapy versus treatment as usual for outpatients with difficult-to-treat depression: study protocol for a parallel group randomized clinical trial (DEPRE-ST).

Childhood trauma Chronic depression Depressive personality disorder Difficult-to-treat depression Persistent depressive disorder Psychotherapy Randomized controlled trial Schema therapy Treatment refractory depression Treatment-resistant depression

Journal

Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253

Informations de publication

Date de publication:
16 Apr 2024
Historique:
received: 16 01 2024
accepted: 28 03 2024
medline: 17 4 2024
pubmed: 17 4 2024
entrez: 16 4 2024
Statut: epublish

Résumé

About one third of patients with depression are in a condition that can be termed as "difficult-to-treat". Some evidence suggests that difficult-to-treat depression is associated with a higher frequency of childhood trauma and comorbid personality disorders or accentuated features. However, the condition is understudied, and the effects of psychotherapy for difficult-to-treat depression are currently uncertain. The aim of this trial is to investigate the beneficial and harmful effects of 30 sessions of individual schema therapy versus treatment as usual for difficult-to-treat depression in the Danish secondary, public mental health sector. In this randomized, multi-centre, parallel-group, superiority clinical trial, 129 outpatients with difficult-to-treat depression will be randomized (1:1) to 30 sessions of individual schema therapy or treatment as usual; in this context mainly group-based, short-term cognitive behaviour or psychodynamic therapy. The primary outcome is the change from baseline in depressive symptoms 12 months after randomization, measured on the observer-rated 6-item Hamilton Rating Scale for Depression. The secondary outcomes are health-related quality of life assessed with the European Quality of Life 5 Dimensions 5 Level Version, functional impairment assessed with the Work and Social Adjustment Scale, psychological wellbeing assessed with the WHO-5 Well-being Index, and negative effects of treatment assessed with the Negative Effects Questionnaire. Exploratory outcomes are improvement on patient self-defined outcomes, personal recovery, anxiety symptoms, anger reactions, metacognitive beliefs about anger, and perseverative negative thinking. Outcomes will be assessed at 6, 12, and 24 months after randomization; the 12-month time-point being the primary time-point of interest. Outcome assessors performing the depression-rating, data managers, statisticians, the data safety and monitoring committee, and conclusion makers for the outcome article will be blinded to treatment allocation and results. To assess cost-effectiveness of the intervention, a health economic analysis will be performed. This trial will provide evidence on the beneficial and harmful effects, as well as the cost-effectiveness of schema therapy versus treatment as usual for outpatients with difficult-to-treat depression. The results can potentially improve treatment for a large and understudied patient group. ClinicalTrials.gov NCT05833087. Registered on 15th April 2023 (approved without prompts for revision on 27th April 2023).

Sections du résumé

BACKGROUND BACKGROUND
About one third of patients with depression are in a condition that can be termed as "difficult-to-treat". Some evidence suggests that difficult-to-treat depression is associated with a higher frequency of childhood trauma and comorbid personality disorders or accentuated features. However, the condition is understudied, and the effects of psychotherapy for difficult-to-treat depression are currently uncertain. The aim of this trial is to investigate the beneficial and harmful effects of 30 sessions of individual schema therapy versus treatment as usual for difficult-to-treat depression in the Danish secondary, public mental health sector.
METHODS METHODS
In this randomized, multi-centre, parallel-group, superiority clinical trial, 129 outpatients with difficult-to-treat depression will be randomized (1:1) to 30 sessions of individual schema therapy or treatment as usual; in this context mainly group-based, short-term cognitive behaviour or psychodynamic therapy. The primary outcome is the change from baseline in depressive symptoms 12 months after randomization, measured on the observer-rated 6-item Hamilton Rating Scale for Depression. The secondary outcomes are health-related quality of life assessed with the European Quality of Life 5 Dimensions 5 Level Version, functional impairment assessed with the Work and Social Adjustment Scale, psychological wellbeing assessed with the WHO-5 Well-being Index, and negative effects of treatment assessed with the Negative Effects Questionnaire. Exploratory outcomes are improvement on patient self-defined outcomes, personal recovery, anxiety symptoms, anger reactions, metacognitive beliefs about anger, and perseverative negative thinking. Outcomes will be assessed at 6, 12, and 24 months after randomization; the 12-month time-point being the primary time-point of interest. Outcome assessors performing the depression-rating, data managers, statisticians, the data safety and monitoring committee, and conclusion makers for the outcome article will be blinded to treatment allocation and results. To assess cost-effectiveness of the intervention, a health economic analysis will be performed.
DISCUSSION CONCLUSIONS
This trial will provide evidence on the beneficial and harmful effects, as well as the cost-effectiveness of schema therapy versus treatment as usual for outpatients with difficult-to-treat depression. The results can potentially improve treatment for a large and understudied patient group.
TRIAL REGISTRATION BACKGROUND
ClinicalTrials.gov NCT05833087. Registered on 15th April 2023 (approved without prompts for revision on 27th April 2023).

Identifiants

pubmed: 38627837
doi: 10.1186/s13063-024-08079-9
pii: 10.1186/s13063-024-08079-9
doi:

Banques de données

ClinicalTrials.gov
['NCT05833087']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

266

Subventions

Organisme : TrygFonden
ID : 149726
Organisme : Region Syddanmark
ID : 1523

Informations de copyright

© 2024. The Author(s).

Références

World Health O. The ICD-10 classification of mental and behavioural disorders: Diagnostic criteria for research. Genève, Switzerland: World Health Organization; 1993. p. 1993.
Van Bronswijk S, Moopen N, Beijers L, Ruhe HG, Peeters F. Effectiveness of psychotherapy for treatment-resistant depression: a meta-analysis and meta-regression. Psychol Med. 2019;49(3):366–79.
pubmed: 30139408 doi: 10.1017/S003329171800199X
Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jönsson B, et al. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 2011;21(9):655–79.
pubmed: 21896369 doi: 10.1016/j.euroneuro.2011.07.018
Mairey I, Rosenkilde S, Klitgaard M, Thygesen L. Sygdomsbyrden i Danmark – sygdomme. Udgivet af Sundhedsstyrelsen. København: Statens Institut for Folkesundhed, Syddansk Universitet. 2022.
Sundhedsstyrrelsen. National klinisk retningsline for non-farmakologisk behandling af unipolar depression. 2016.
McAllister-Williams RH, Arango C, Blier P, Demyttenaere K, Falkai P, Gorwood P, et al. The identification, assessment and management of difficult-to-treat depression: An international consensus statement. J Affect Disord. 2020;267:264–82.
pubmed: 32217227 doi: 10.1016/j.jad.2020.02.023
Demyttenaere K, Van Duppen Z. The Impact of (the Concept of) Treatment-Resistant Depression: An Opinion Review. Int J Neuropsychopharmacol. 2019;22(2):85–92.
pubmed: 29961822 doi: 10.1093/ijnp/pyy052
Moeller SB, Gbyl K, Hjorthøj C, Andreasen M, Austin SF, Buchholtz PE, et al. Treatment of difficult-to-treat depression – clinical guideline for selected interventions. Nord J Psychiatry. 2022;76(3):177–88.
pubmed: 34455900 doi: 10.1080/08039488.2021.1952303
Trevino K, McClintock SM, McDonald Fischer N, Vora A, Husain MM. Defining treatment-resistant depression: a comprehensive review of the literature. Ann Clin Psychiatry. 2014;26(3):222–32.
pubmed: 25166485
Gibson TB, Jing Y, Smith Carls G, Kim E, Bagalman JE, Burton WN, et al. Cost burden of treatment resistance in patients with depression. Am J Manag Care. 2010;16(5):370–7.
pubmed: 20469957
Pfeiffer PN, Kim HM, Ganoczy D, Zivin K, Valenstein M. Treatment-Resistant Depression and Risk of Suicide. Suicide and Life-Threatening Behavior. 2013;43(4):356–65.
pubmed: 23510005 doi: 10.1111/sltb.12022
Carney RM, Freedland KE. Treatment-resistant depression and mortality after acute coronary syndrome. Am J Psychiatry. 2009;166(4):410–7.
pubmed: 19289455 pmcid: 3465939 doi: 10.1176/appi.ajp.2008.08081239
Jaffe DH, Rive B, Denee TR. The humanistic and economic burden of treatment-resistant depression in Europe: a cross-sectional study. BMC Psychiatry. 2019;19(1):247.
pubmed: 31391065 pmcid: 6686569 doi: 10.1186/s12888-019-2222-4
Barnhofer T, Brennan K, Crane C, Duggan D, Williams JM. A comparison of vulnerability factors in patients with persistent and remitting lifetime symptom course of depression. J Affect Disord. 2014;152–154:155–61.
pubmed: 24183488 pmcid: 3878770 doi: 10.1016/j.jad.2013.09.001
Negele A, Kaufhold J, Kallenbach L, Leuzinger-Bohleber M. Childhood trauma and its relation to chronic depression in adulthood. Depress Res Treat. 2015;2015: 650804.
pubmed: 26693349 pmcid: 4677006
Riso LP, Miyatake RK, Thase ME. The search for determinants of chronic depression: a review of six factors. J Affect Disord. 2002;70(2):103–15.
pubmed: 12117622 doi: 10.1016/S0165-0327(01)00376-7
Nelson J, Klumparendt A, Doebler P, Ehring T. Childhood maltreatment and characteristics of adult depression: meta-analysis. Br J Psychiatry. 2017;210(2):96–104.
pubmed: 27908895 doi: 10.1192/bjp.bp.115.180752
Köhler S, Chrysanthou S, Guhn A, Sterzer P. Differences between chronic and nonchronic depression: Systematic review and implications for treatment. Depress Anxiety. 2019;36(1):18–30.
pubmed: 30300454 doi: 10.1002/da.22835
Hölzel L, Härter M, Reese C, Kriston L. Risk factors for chronic depression — A systematic review. J Affect Disord. 2011;129(1):1–13.
pubmed: 20488546 doi: 10.1016/j.jad.2010.03.025
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR). Washington: American Psychiatric Association; 2000.
Jobst A, Brakemeier EL, Buchheim A, Caspar F, Cuijpers P, Ebmeier KP, et al. European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe. Eur Psychiatry. 2016;33:18–36.
pubmed: 26854984 doi: 10.1016/j.eurpsy.2015.12.003
Peeters N, van Passel B, Krans J. The effectiveness of schema therapy for patients with anxiety disorders, OCD, or PTSD: A systematic review and research agenda. Br J Clin Psychol. 2022;61(3):579–97.
pubmed: 34296767 doi: 10.1111/bjc.12324
Joshua PR, Lewis V, Kelty SF, Boer DP. Is schema therapy effective for adults with eating disorders? A systematic review into the evidence. Cogn Behav Ther. 2023;52(3):213–31.
pubmed: 36633136 doi: 10.1080/16506073.2022.2158926
Setkowski K, Palantza C, van Ballegooijen W, Gilissen R, Oud M, Cristea IA, et al. Which psychotherapy is most effective and acceptable in the treatment of adults with a (sub)clinical borderline personality disorder? A systematic review and network meta-analysis. Psychol Med. 2023;53(8):3261–80.
pubmed: 37203447 pmcid: 10277776 doi: 10.1017/S0033291723000685
Carter JD, McIntosh VV, Jordan J, Porter RJ, Frampton CM, Joyce PR. Psychotherapy for depression: a randomized clinical trial comparing schema therapy and cognitive behavior therapy. J Affect Disord. 2013;151(2):500–5.
pubmed: 23870427 doi: 10.1016/j.jad.2013.06.034
Kopf-Beck J, Müller CL, Tamm J, Fietz J, Rek N, Just L, et al. Effectiveness of Schema Therapy versus Cognitive Behavioral Therapy versus Supportive Therapy for Depression in Inpatient and Day Clinic Settings: A Randomized Clinical Trial. Psychother Psychosom. 2024;93(1):24-35.
Malogiannis IA, Arntz A, Spyropoulou A, Tsartsara E, Aggeli A, Karveli S, et al. Schema therapy for patients with chronic depression: A single case series study. J Behav Ther Exp Psychiatry. 2014;45(3):319–29.
pubmed: 24650608 doi: 10.1016/j.jbtep.2014.02.003
Renner F, Arntz A, Peeters FPML, Lobbestael J, Huibers MJH. Schema therapy for chronic depression: Results of a multiple single case series. J Behav Ther Exp Psychiatry. 2016;51:66–73.
pubmed: 26780673 doi: 10.1016/j.jbtep.2015.12.001
Davies P, Ijaz S, Williams CJ, Kessler D, Lewis G, Wiles N. Pharmacological interventions for treatment-resistant depression in adults. Cochrane Database Syst Rev. 2019;12(12):CD010557.
Scott F, Hampsey E, Gnanapragasam S, Carter B, Marwood L, Taylor RW, et al. Systematic review and meta-analysis of augmentation and combination treatments for early-stage treatment-resistant depression. J Psychopharmacol. 2023;37(3):268–78.
pubmed: 35861202 doi: 10.1177/02698811221104058
Cuijpers P, van Straten A, Schuurmans J, van Oppen P, Hollon SD, Andersson G. Psychotherapy for chronic major depression and dysthymia: A meta-analysis. Clin Psychol Rev. 2010;30(1):51–62.
pubmed: 19781837 doi: 10.1016/j.cpr.2009.09.003
Negt P, Brakemeier EL, Michalak J, Winter L, Bleich S, Kahl KG. The treatment of chronic depression with cognitive behavioral analysis system of psychotherapy: a systematic review and meta-analysis of randomized-controlled clinical trials. Brain Behav. 2016;6(8): e00486.
pubmed: 27247856 pmcid: 4864084 doi: 10.1002/brb3.486
Zakhour S, Nardi AE, Levitan M, Appolinario JC. Cognitive-behavioral therapy for treatment-resistant depression in adults and adolescents: a systematic review. Trends Psychiatry Psychother. 2020;42(1):92–101.
pubmed: 32130308 doi: 10.1590/2237-6089-2019-0033
Li JM, Zhang Y, Su WJ, Liu LL, Gong H, Peng W, et al. Cognitive behavioral therapy for treatment-resistant depression: A systematic review and meta-analysis. Psychiatry Res. 2018;268:243–50.
pubmed: 30071387 doi: 10.1016/j.psychres.2018.07.020
Ijaz S, Davies P, Williams CJ, Kessler D, Lewis G, Wiles N. Psychological therapies for treatment-resistant depression in adults. Cochrane Database Syst Rev. 2018;5(5):Cd010558.
Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–6.
pubmed: 18436948 pmcid: 2335261 doi: 10.1136/bmj.39489.470347.AD
Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. J Clin Epidemiol. 2008;61(8):763–9.
pubmed: 18411040 doi: 10.1016/j.jclinepi.2007.10.007
Imberger G, Thorlund K, Gluud C, Wetterslev J. False-positive findings in Cochrane meta-analyses with and without application of trial sequential analysis: an empirical review. BMJ Open. 2016;6(8): e011890.
pubmed: 27519923 pmcid: 4985805 doi: 10.1136/bmjopen-2016-011890
Wetterslev J, Jakobsen JC, Gluud C. Trial Sequential Analysis in systematic reviews with meta-analysis. BMC Med Res Methodol. 2017;17(1):39.
pubmed: 28264661 pmcid: 5397700 doi: 10.1186/s12874-017-0315-7
Wetterslev J, Thorlund K, Brok J, Gluud C. Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis. J Clin Epidemiol. 2008;61(1):64–75.
pubmed: 18083463 doi: 10.1016/j.jclinepi.2007.03.013
Cuijpers P, Miguel C, Harrer M, Plessen CY, Ciharova M, Ebert D, et al. Cognitive behavior therapy vs. control conditions, other psychotherapies, pharmacotherapies and combined treatment for depression: a comprehensive meta-analysis including 409 trials with 52,702 patients. World Psychiatry. 2023;22(1):105–15.
Cuijpers P, Miguel C, Harrer M, Plessen CY, Ciharova M, Papola D, et al. Psychological treatment of depression: A systematic overview of a “Meta-Analytic Research Domain.” J Affect Disord. 2023;335:141–51.
pubmed: 37178828 doi: 10.1016/j.jad.2023.05.011
Arntz A, Jacob G. Schema therapy in practice: An introductory guide to the schema mode approach. Hoboken, NJ, US: Wiley Blackwell; 2013. ix, 265-ix, p.
Renner F, Arntz A, Leeuw I, Huibers M. Treatment for Chronic Depression Using Schema Therapy. Clin Psychol Sci Pract. 2013;20(2):166–80.
doi: 10.1111/cpsp.12032
Bishop A, Younan R, Low J, Pilkington PD. Early maladaptive schemas and depression in adulthood: A systematic review and meta-analysis. Clin Psychol Psychother. 2022;29(1):111–30.
pubmed: 34131990 doi: 10.1002/cpp.2630
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.
Danske Regioner. Pakkeforløb for periodisk depression [Available from: https://www.regioner.dk/media/11312/pakkeforloeb-for-periodisk-depression.pdf Accessed 1st Dec 2023.
Danish Patient Compensation. [Available from: https://eng.patienterstatningen.dk/ Accessed 4 Jan 2024.
Licht RW, Qvitzau S, Allerup P, Bech P. Validation of the Bech-Rafaelsen Melancholia Scale and the Hamilton Depression Scale in patients with major depression; is the total score a valid measure of illness severity? Acta Psychiatr Scand. 2005;111(2):144–9.
pubmed: 15667434 doi: 10.1111/j.1600-0447.2004.00440.x
Peasgood T, Brazier J, Papaioannou D. A systematic review of the validity and responsiveness of EQ-5D and SF-6D for depression and anxiety. HEDS Discussion paper 12/15. 2012.
Sørensen J, Davidsen M, Gudex C, Pedersen KM, Brønnum-Hansen H. Danish EQ-5D population norms. Scand J Public Health. 2009;37(5):467–74.
pubmed: 19535407 doi: 10.1177/1403494809105286
Mundt JC, Marks IM, Shear MK, Greist JH. The Work and Social Adjustment Scale: a simple measure of impairment in functioning. Br J Psychiatry. 2002;180:461–4.
pubmed: 11983645 doi: 10.1192/bjp.180.5.461
Topp CW, Østergaard SD, Søndergaard S, Bech P. The WHO-5 Well-Being Index: a systematic review of the literature. Psychother Psychosom. 2015;84(3):167–76.
pubmed: 25831962 doi: 10.1159/000376585
Rozental A, Castonguay L, Dimidjian S, Lambert M, Shafran R, Andersson G, et al. Negative effects in psychotherapy: commentary and recommendations for future research and clinical practice. BJPsych Open. 2018;4(4):307–12.
pubmed: 30083384 pmcid: 6066991 doi: 10.1192/bjo.2018.42
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(5):559–72.
pubmed: 30871650 doi: 10.1017/S1352465819000018
Williams J, Leamy M, Bird V, Le Boutillier C, Norton S, Pesola F, et al. Development and evaluation of the INSPIRE measure of staff support for personal recovery. Soc Psychiatry Psychiatr Epidemiol. 2015;50(5):777–86.
pubmed: 25409867 doi: 10.1007/s00127-014-0983-0
Moeller SB, Gondan M, Austin SF, Slade M, Simonsen S. National norms of mental health for Denmark. Nord J Psychiatry. 2023;77(6):617–23.
pubmed: 37129238 doi: 10.1080/08039488.2023.2202637
Williams J, Leamy M, Bird V, Harding C, Larsen J, Le Boutillier C, et al. Measures of the recovery orientation of mental health services: systematic review. Soc Psychiatry Psychiatr Epidemiol. 2012;47(11):1827–35.
pubmed: 22322983 doi: 10.1007/s00127-012-0484-y
Ashworth M, Shepherd M, Christey J, Matthews V, Wright K, Parmentier H, et al. A client-generated psychometric instrument: The development of “PSYCHLOPS.” Couns Psychother Res. 2004;4(2):27–31.
doi: 10.1080/14733140412331383913
Ashworth M, Evans C, Clement S. Measuring psychological outcomes after cognitive behaviour therapy in primary care: A comparison between a new patient-generated measure “PSYCHLOPS” (Psychological Outcome Profiles) and “HADS” (Hospital Anxiety and Depression Scale). J Ment Health. 2009;18(2):169–77.
doi: 10.1080/09638230701879144
Ashworth M, Robinson SI, Godfrey EL, Shepherd M, Evans CH, Seed PT, et al., editors. Measuring mental health outcomes in primary care: The psychometric properties of a new patient-generated outcome measure, 'PSYCHLOPS' ('psychological outcome profiles')2005.
Kannis-Dymand L, Salguero JM, Ramos-Cejudo J, Novaco RW. Dimensions of Anger Reactions-Revised (DAR-R): Validation of a brief anger measure in Australia and Spain. J Clin Psychol. 2019;75(7):1233–48.
pubmed: 30758849 doi: 10.1002/jclp.22757
Moeller SB, Juul S, Arendt ITP. The Short Version of the Metacognitive Anger Processing Scale (MAP-SV) - initial psychometric testing. Behav Cogn Psychother. 2022;50(1):117–21.
pubmed: 34078508 doi: 10.1017/S1352465821000199
Ehring T, Zetsche U, Weidacker K, Wahl K, Schönfeld S, Ehlers A. The Perseverative Thinking Questionnaire (PTQ): validation of a content-independent measure of repetitive negative thinking. J Behav Ther Exp Psychiatry. 2011;42(2):225–32.
pubmed: 21315886 pmcid: 3042595 doi: 10.1016/j.jbtep.2010.12.003
Moeller SB, Larsen PV, Arendt I-MTP, Ehring T, Reinholt N, Hvenegaard M, et al. Validation of the Danish Version of Perseverative Thinking Questionnaire (PTQ) – Introducing the PTQ Short Version. Psychol Test Adapt Dev. 2023;4(1):310–8.
Bech P, Austin SF, Lau ME. Patient reported outcome measures (PROMs): examination of the psychometric properties of two measures for burden of symptoms and quality of life in patients with depression or anxiety. Nord J Psychiatry. 2018;72(4):251–8.
pubmed: 29546787 doi: 10.1080/08039488.2018.1451918
Østergaard SD, Papakostas GI, Fava M. Depression: Response and Remission. In: Stolerman IP, Price LH, editors. Encyclopedia of Psychopharmacology. Berlin, Heidelberg: Springer Berlin Heidelberg; 2015. p. 505-9.
Lobbestael J, van Vreeswijk M, Spinhoven P, Schouten E, Arntz A. Reliability and validity of the short Schema Mode Inventory (SMI). Behav Cogn Psychother. 2010;38(4):437–58.
pubmed: 20487590 doi: 10.1017/S1352465810000226
Reiss N, Krampen D, Christoffersen P, Bach B. Reliability and validity of the Danish version of the Schema Mode Inventory (SMI). Psychol Assess. 2016;28(3):e19–26.
pubmed: 26375430 doi: 10.1037/pas0000154
Bach B, Simonsen E, Christoffersen P, Kriston L. The Young Schema Questionnaire 3 Short Form (YSQ-S3): Psychometric properties and association with personality disorders in a Danish mixed sample. Eur J Psychol Assess. 2017;33(2):134–43.
doi: 10.1027/1015-5759/a000272
Fekadu A, Wooderson S, Donaldson C, Markopoulou K, Masterson B, Poon L, et al. A multidimensional tool to quantify treatment resistance in depression: the Maudsley staging method. J Clin Psychiatry. 2009;70(2):177–84.
pubmed: 19192471 doi: 10.4088/JCP.08m04309
Bernstein DP, Stein JA, Newcomb MD, Walker E, Pogge D, Ahluvalia T, et al. Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse Negl. 2003;27(2):169–90.
pubmed: 12615092 doi: 10.1016/S0145-2134(02)00541-0
Kongerslev MT, Bach B, Rossi G, Trauelsen AM, Ladegaard N, Løkkegaard SS, et al. Psychometric validation of the Childhood Trauma Questionnaire-Short Form (CTQ-SF) in a Danish clinical sample. Child Abuse Negl. 2019;94: 104026.
pubmed: 31154112 doi: 10.1016/j.chiabu.2019.104026
Dozois DJ, Westra HA. Development of the Anxiety Change Expectancy Scale (ACES) and validation in college, community, and clinical samples. Behav Res Ther. 2005;43(12):1655–72.
pubmed: 15922290 doi: 10.1016/j.brat.2004.12.001
Eddington KM, Dozois DJ, Backs-Dermott BJ. Evaluation of the internal consistency, factor structure, and validity of the Depression Change Expectancy Scale. Assessment. 2014;21(5):607–17.
pubmed: 24379447 doi: 10.1177/1073191113517929
Østergaard SD, Bech P, Miskowiak KW. Fewer study participants needed to demonstrate superior antidepressant efficacy when using the Hamilton melancholia subscale (HAM-D
pubmed: 25487682 doi: 10.1016/j.jad.2014.10.047
Timmerby N, Andersen JH, Søndergaard S, Østergaard SD, Bech P. A Systematic Review of the Clinimetric Properties of the 6-Item Version of the Hamilton Depression Rating Scale (HAM-D6). Psychother Psychosom. 2017;86(3):141–9.
pubmed: 28490031 doi: 10.1159/000457131
Rush AJ, South C, Jain S, Agha R, Zhang M, Shrestha S, et al. Clinically significant changes in the 17- and 6-item hamilton rating scales for depression: A STAR*D Report. Neuropsychiatr Dis Treat. 2021;17:2333–45.
pubmed: 34295161 pmcid: 8290193 doi: 10.2147/NDT.S305331
Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175–91.
pubmed: 17695343 doi: 10.3758/BF03193146
Sealed Envelope Ltd. Create a blocked randomization list. 2022 [Available from: https://sealedenvelope.com/simple-randomiser/v1/lists Accessed 10 Feb 2023.
Juul S, Gluud C, Simonsen S, Frandsen FW, Kirsch I, Jakobsen JC. Blinding in randomised clinical trials of psychological interventions: a retrospective study of published trial reports. BMJ Evidence-Based Medicine. 2021;26(3):109.
pubmed: 32998993 doi: 10.1136/bmjebm-2020-111407
Committee for Medicinal Products for Human Use. Guideline on adjustment for baseline covariates in clinical trials. London/Amsterdam: European Medicines Agency; 2015.
International council for harmonisation of tehcnical requirements for pharmaceuticals for human use. ICH Harmonised guideline. Good Clinical Practice (GCP) E6(R3). Report No.: Draft version, endorsed on 19 May 2023.
Jakobsen JC, Gluud C, Winkel P, Lange T, Wetterslev J. The thresholds for statistical and clinical significance – a five-step procedure for evaluation of intervention effects in randomised clinical trials. BMC Med Res Methodol. 2014;14(1):34.
pubmed: 24588900 pmcid: 4015863 doi: 10.1186/1471-2288-14-34
Committee for Medicinal Products for Human Use. Guideline on the investigation of subgroups in confirmatory clinical trials.  London/Amsterdam: Eur Med Agency. 2019.
Wolbers M, Noci A, Delmar P, Gower-Page C, Yiu S, Bartlett JW. Standard and reference-based conditional mean imputation. Pharm Stat. 2022;21(6):1246–57.
pubmed: 35587109 pmcid: 9790242 doi: 10.1002/pst.2234
Linden M, Schermuly-Haupt ML. Definition, assessment and rate of psychotherapy side effects. World Psychiatry. 2014;13(3):306–9.
pubmed: 25273304 pmcid: 4219072 doi: 10.1002/wps.20153

Auteurs

Ida-Marie T P Arendt (ITP)

Department of Psychology, University of Southern Denmark, Campusvej 55, 5230, Odense, Denmark. imarendt@health.sdu.dk.
Department of Trauma- and Torture Survivors, Mental Health Services in the Region of Southern Denmark, Vestre Engvej 51, 7100, Vejle, Denmark. imarendt@health.sdu.dk.

Matthias Gondan (M)

Department of Psychology, Universität Innsbruck, Innrain 52, 6020, Innsbruck, Austria.

Sophie Juul (S)

Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark.
Research Unit of Stolpegaard Psychotherapy Centre, Mental Health Services, Capital Region of Denmark, Stolpegaardsvej 20, 2820, Gentofte, Denmark.

Lene Halling Hastrup (LH)

Psychiatric Research Unit, Psychiatry in Region Zealand, Faelledvej 6, 4200, Slagelse, Denmark.
Danish Centre for Health Economics (DaCHE), University of Southern Denmark, Campusvej 55, 5230, Odense M, Denmark.

Carsten Hjorthøj (C)

Copenhagen Research Center for Mental Health - CORE, Mental Health Services, Capital Region of Denmark, Copenhagen, Denmark.
Department of Public Health, Section of Epidemiology, University of Copenhagen, Øster Farimagsgade 5, 1353, Copenhagen K, Denmark.

Bo Bach (B)

Department of Psychology, University of Copenhagen, Øster Farimagsgade 2a, 1353, Copenhagen K, Denmark.
Center for Personality Disorder Research, Mental Health Services in Region Zealand, Fælledvej 6, 4Th Floor, 4200, Slagelse, Denmark.

Poul Videbech (P)

Centre for Neuropsychiatric Depression Research, Nordstjernevej 41, Mental Health Centre Glostrup, 2600, Glostrup, Denmark.

Martin Balslev Jørgensen (MB)

Psychiatric Centre Copenhagen, Mental Health Services, Capital Region of Denmark, Frederiksberg Hospital, Hovedvejen 17, 2000, Frederiksberg, Denmark.
Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark.

Stine Bjerrum Moeller (SB)

Department of Psychology, University of Southern Denmark, Campusvej 55, 5230, Odense, Denmark.
Department of Trauma- and Torture Survivors, Mental Health Services in the Region of Southern Denmark, Vestre Engvej 51, 7100, Vejle, Denmark.

Classifications MeSH