Schema Therapy for Patients With Chronic Treatment Resistant Depression

NCT05833087 | Recruiting

• 1 other identifier: 20220033
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 6

Brief Summary

The goal of this clinical study is to test a particular form of psychotherapy, called schema therapy, for people with difficult-to-treat depression (when depression is very lengthy or difficult to cure with antidepressive medication). Researchers will compare the group of participants receiving schema therapy to a group receiving standard psychotherapeutic treatment to see if schema therapy is more effective on depression symptoms and other important issues for the participant. The main question the study aims to answer is: \- Can schema therapy be a more effective treatment for difficult-to-treat depression than other forms of psychotherapy offered in psychiatry today? People who have difficult-to-treat depression are a special group of patients who are more strained in a wide range of areas of life than other people with depression. They also more often have childhood trauma, as well as simultaneous personality disorder or personality traits that brings challenges in everyday life. Currently we can not offer a sufficiently effective psychiatric treatment for this group of people. Schema therapy was developed to help patients who do not have sufficient effect of the usual psychotherapeutic treatments. It also addresses personality disorders or problematic traits and childhood trauma directly in the therapy. The project will include 129 participants in total, of which half will receive schema therapy. Treatment is provided at six psychiatric centers in both the Southern and the Capital Regions of Denmark. Participants receiving schema therapy will be given 30 sessions of weekly therapy, as well as the opportunity for the rest of the standard care package in the Danish secondary mental health system, that is, treatment with psychopharmacological medicine and meetings with next-to-kin and other parts of the participant's support system. Participants receiving the standard treatment will receive about 6-20 sessions of individual or group therapy with a range of other psychotherapies that are not schema therapy, as well as the other parts of the standard care package as listed above. If schema therapy proves to be more effective for treatment of difficult-to-treat depression than the treatment offered today, it may give rise to more extended use of schema therapy in and outside psychiatry. This means that the toolbox for the treatment of difficult-to-treat depression is expanded with a new specialized and effective psychotherapeutic tool.

Conditions

Treatment Resistant Depression; Chronic Depression

Keywords

treatment resistant depression; schema therapy; psychotherapy; difficult-to-treat depression; chronic depression; clinical trial; randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Change from baseline in depression symptoms on the clinician-rated Hamilton-6 Rating Scale for Depression at 12 months after baseline measurements

  6-item clinician rated instrument

  From baseline measurements to end of treatment (of schema therapy) at 12 months

Secondary Outcomes (46)

• Change from baseline in depression symptoms on the Hamilton-6 Rating Scale for Depression at 6 months after baseline measurements

  From baseline measurements to end of treatment (Treatment at usual) at 6 months

• Change from baseline in depression symptoms on the Hamilton-6 Rating Scale for Depression at 24 months after baseline measurements

  From baseline measurements to after 24 months

• Change from baseline in subjective functional impairment as measured on the Work and Social Adjustment Scale (WSAS) at 6 months after baseline measurements

  From baseline measurements to end of treatment (Treatment at usual) at 6 months

• Change from baseline in subjective functional impairment as measured on the Work and Social Adjustment Scale (WSAS) at 12 months after baseline measurements

  From baseline measurements to end of treatment (of schema therapy) at 12 months

• Change from baseline in subjective functional impairment as measured on the Work and Social Adjustment Scale (WSAS) at 24 months after baseline measurements

  From baseline measurements to after 24 months

Other Outcomes (2)

• Treatments for depression in earlier and current depressive episode as predictors of treatment effect

  Collected at baseline only

• Childhood adversity, as measured on the Childhood Trauma Questionnaire (CTQ) as predictor of treatment effect

  Collected at baseline only

Study Arms (2)

Schema therapy

EXPERIMENTAL

The participants in this arm will receive up to 30 individual, weekly sessions of consecutive Schema Therapy (ST). A treatment manual for ST has been written for the study, based on former studies of ST on chronic depression as well as the manual for a major clinical trial on ST for avoidant personality disorder.

Behavioral: Schema therapy; Other: Standard care package content

Treatment as Usual

ACTIVE COMPARATOR

Patients with moderate-severe depression in the Danish secondary psychiatric sector are treated according to standard 'treatment packages', in the 'Main Function' offering from 6 to 16 weekly sessions of psychotherapy, in group or individually, typically Cognitive Behavioral Therapy, psychodynamic or interpersonal therapy or other evidence-based therapies.

Behavioral: Other psychotherapy; Other: Standard care package content

Interventions

Schema therapy BEHAVIORAL

30 sessions of schema therapy. The therapy was developed by Jeffrey Young and others and encompasses elements from cognitive behavioral, psychodynamic, and gestalt therapies, as well as attachment theory.

Schema therapy

Other psychotherapy BEHAVIORAL

In this arm, psychotherapy can be psychodynamic, cognitive behavioral, interpersonal or other evidence-based psychotherapies, aimed at changing cognitions, behavior, improve social relations and uncover unconstructive psychological patterns.

Treatment as Usual

Standard care package content OTHER

Standard care packages: The patient is offered prescription and monitoring of psychopharmacological treatment of up to 5 hours by a psychiatrist, when appropriate. Additionally, patients have up to 3 hours of preparatory and diagnostic sessions and up to 4 hours of meetings with the participation of next-of-kin and/or collaboration partners in other public instances. Expanded package: In one center, specialized treatment is offered for difficult-to-treat depression. Up to 9 months of psychotherapy is offered, as well as close follow-up on adjustment in medicine.

Schema therapy; Treatment as Usual

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants should meet the diagnosis of chronic or treatment-resistant depression as follows:
• Clinical major depression as measured by the M.I.N.I. diagnostic interview: duration minimum two years OR persistent after = 2 trials of antidepressants from different classes, in an adequate dosage and time period (= 4 weeks) OR moderate treatment resistance as measured on the MSM-scale, score \> 6
• Minimum a score of 9 points on the Hamilton Rating Scale for Depression 6 (HAMD-6), corresponding to moderate to severe depression

You may not qualify if:

• Alcohol or substance abuse
• Bipolar or psychotic disorder
• Acute suicidal risk
• Mental disability (estimated IQ \< 70)
• Non-Danish speaker

Sponsors & Collaborators

• Region of Southern Denmark: lead
• TrygFonden, Denmark: collaborator
• Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital: collaborator

Study Sites (6)

Psychotherapeutic Out-patient Clinic, Psychiatric Center Ballerup, Mental Health Services, Capital Region of Denmark

Ballerup Municipality, 2750, Denmark

RECRUITING

Outpatient clinic for Affective Disorders, Frederiksberg, Capital Region of Denmark Psychiatry

Copenhagen, 2000, Denmark

NOT YET RECRUITING

Psychotherapeutic Out-patient Clinic, Psychiatric Center Copenhagen/Nannasgade, Mental Health Services, Capital Region of Denmark

Copenhagen, 2200, Denmark

RECRUITING

Psychotherapeutic Clinic Frederiksberg, Psychiatric Center Copenhagen, Mental Health Services, Capital Region of Denmark

Frederiksberg, Denmark

RECRUITING

Local Psychiatry Odense, Region of Southern Denmark Psychiatry

Odense, Denmark

RECRUITING

Psychiatric Unit Odense-Svendborg, Southern Region of Denmark Psychiatry

Svendborg, 5700, Denmark

NOT YET RECRUITING

Related Publications (21)

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• Ostergaard SD, Bech P, Miskowiak KW. Fewer study participants needed to demonstrate superior antidepressant efficacy when using the Hamilton melancholia subscale (HAM-D(6)) as outcome measure. J Affect Disord. 2016 Jan 15;190:842-845. doi: 10.1016/j.jad.2014.10.047. Epub 2014 Nov 7.

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• Timmerby N, Andersen JH, Sondergaard S, Ostergaard 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):141-149. doi: 10.1159/000457131. Epub 2017 May 11.

  PMID: 28490031 BACKGROUND

• 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 Aug;26(3):222-32.

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• 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 Jan;152-154:155-61. doi: 10.1016/j.jad.2013.09.001. Epub 2013 Sep 20.

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• Demyttenaere K, Van Duppen Z. The Impact of (the Concept of) Treatment-Resistant Depression: An Opinion Review. Int J Neuropsychopharmacol. 2019 Feb 1;22(2):85-92. doi: 10.1093/ijnp/pyy052.

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• Fekadu A, Wooderson S, Donaldson C, Markopoulou K, Masterson B, Poon L, Cleare AJ. A multidimensional tool to quantify treatment resistance in depression: the Maudsley staging method. J Clin Psychiatry. 2009 Feb;70(2):177-84. doi: 10.4088/jcp.08m04309. Epub 2009 Jan 27.

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• Kohler S, Chrysanthou S, Guhn A, Sterzer P. Differences between chronic and nonchronic depression: Systematic review and implications for treatment. Depress Anxiety. 2019 Jan;36(1):18-30. doi: 10.1002/da.22835. Epub 2018 Oct 9.

  PMID: 30300454 BACKGROUND

• Lim CR, Barlas J. The effects of Toxic Early Childhood Experiences on Depression according to Young Schema Model: A Scoping Review. J Affect Disord. 2019 Mar 1;246:1-13. doi: 10.1016/j.jad.2018.12.006. Epub 2018 Dec 10.

  PMID: 30562652 BACKGROUND

• Malogiannis IA, Arntz A, Spyropoulou A, Tsartsara E, Aggeli A, Karveli S, Vlavianou M, Pehlivanidis A, Papadimitriou GN, Zervas I. Schema therapy for patients with chronic depression: a single case series study. J Behav Ther Exp Psychiatry. 2014 Sep;45(3):319-29. doi: 10.1016/j.jbtep.2014.02.003. Epub 2014 Feb 24.

  PMID: 24650608 BACKGROUND

• Renner F, Arntz A, Peeters FP, Lobbestael J, Huibers MJ. Schema therapy for chronic depression: Results of a multiple single case series. J Behav Ther Exp Psychiatry. 2016 Jun;51:66-73. doi: 10.1016/j.jbtep.2015.12.001. Epub 2015 Dec 8.

  PMID: 26780673 BACKGROUND

• Moeller SB, Gbyl K, Hjorthoj C, Andreasen M, Austin SF, Buchholtz PE, Fonss L, Hjerrild S, Hogervorst L, Jorgensen MB, Ladegaard N, Martiny K, Meile J, Packness A, Sigaard KR, Straarup K, Straszek SPV, Soerensen CH, Welcher B, Videbech P. Treatment of difficult-to-treat depression - clinical guideline for selected interventions. Nord J Psychiatry. 2022 Apr;76(3):177-188. doi: 10.1080/08039488.2021.1952303. Epub 2021 Aug 28.

  PMID: 34455900 BACKGROUND

• Riso LP, Miyatake RK, Thase ME. The search for determinants of chronic depression: a review of six factors. J Affect Disord. 2002 Jul;70(2):103-15. doi: 10.1016/s0165-0327(01)00376-7.

  PMID: 12117622 BACKGROUND

• Rozental A, Castonguay L, Dimidjian S, Lambert M, Shafran R, Andersson G, Carlbring P. Negative effects in psychotherapy: commentary and recommendations for future research and clinical practice. BJPsych Open. 2018 Jul 25;4(4):307-312. doi: 10.1192/bjo.2018.42. eCollection 2018 Jul.

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• Ruhe HG, van Rooijen G, Spijker J, Peeters FP, Schene AH. Staging methods for treatment resistant depression. A systematic review. J Affect Disord. 2012 Mar;137(1-3):35-45. doi: 10.1016/j.jad.2011.02.020. Epub 2011 Mar 23.

  PMID: 21435727 BACKGROUND

• Yakin D, Grasman R, Arntz A. Schema modes as a common mechanism of change in personality pathology and functioning: Results from a randomized controlled trial. Behav Res Ther. 2020 Mar;126:103553. doi: 10.1016/j.brat.2020.103553. Epub 2020 Jan 16.

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• Jobst A, Brakemeier EL, Buchheim A, Caspar F, Cuijpers P, Ebmeier KP, Falkai P, Jan van der Gaag R, Gaebel W, Herpertz S, Kurimay T, Sabass L, Schnell K, Schramm E, Torrent C, Wasserman D, Wiersma J, Padberg F. European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe. Eur Psychiatry. 2016 Mar;33:18-36. doi: 10.1016/j.eurpsy.2015.12.003. Epub 2016 Feb 6.

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• Renner F, Lobbestael J, Peeters F, Arntz A, Huibers M. Early maladaptive schemas in depressed patients: stability and relation with depressive symptoms over the course of treatment. J Affect Disord. 2012 Feb;136(3):581-90. doi: 10.1016/j.jad.2011.10.027. Epub 2011 Nov 25.

  PMID: 22119093 BACKGROUND

• Arendt ITP, Gondan M, Juul S, Hastrup LH, Hjorthoj C, Moeller SB. Statistical analysis plan for a parallel group randomized clinical trial comparing schema therapy versus treatment as usual for outpatients with difficult-to-treat depression (DEPRE-ST). Trials. 2025 Sep 1;26(1):334. doi: 10.1186/s13063-025-09012-4.

  PMID: 40890784 DERIVED

• Arendt ITP, Gondan M, Juul S, Hastrup LH, Hjorthoj C, Bach B, Videbech P, Jorgensen MB, Moeller SB. Schema therapy versus treatment as usual for outpatients with difficult-to-treat depression: study protocol for a parallel group randomized clinical trial (DEPRE-ST). Trials. 2024 Apr 16;25(1):266. doi: 10.1186/s13063-024-08079-9.

  PMID: 38627837 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Schema Therapy

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Stine B. Moeller, PhD

  Region of Southern Denmark Psychiatry; University of Southern Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ida-Marie T. P. Arendt

CONTACT

+4551909649; imarendt@health.sdu.dk

Stine B. Møller, PhD

CONTACT

+4551553898; stinebm@health.sdu.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessors are blinded to treatment condition and to the hypotheses of the study. Different assessors will be assigned at each measurement time point. Participants and therapists are instructed to withhold information about the treatment from the research team. The research team has no clinical contact with the participants from assessment to end of intervention, and the assessors have no knowledge about the participant's randomization status at the end of intervention. Statistical analyses will be made with the two intervention groups coded as 'A' and 'B'. The results will remain coded when writing the outcome section of the relevant scientific articles, and the code will only be broken at the conclusion of this write-up.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Research Unit, Associate Professor

Model Details: The study is a multi-center, two-arm, parallel group, assessor-blinded, randomized controlled superiority study.

Study Record Dates

• First Submitted: April 15, 2023
• First Posted: April 27, 2023
• Study Start: April 17, 2023
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): July 31, 2029
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be available from 6 months after the publication of results of the follow-up study. Data will discontinue to be available 5 years after the completion of the study in its entirety due to law-enforced deletion of primary data.
• Access Criteria: IPD will be shared at reasonable request by any serious researcher who can procure a detailed protocol for the use of the data. Data will be shared for the use in publication of peer reviewed articles pertaining to effects of psychotherapy. Data will be shared via a secure VPN. Requests will be reviewed by the Project Investigator, Stine Bjerrum Moeller

Locations

DK (6)