Improving Treatment of Major Depressive Disorder by Reducing Negative Future-Oriented Mental Imagery

Major Depressive Disorder Clinical Trial

— PROFIT  

Official title:

Improving Treatment of Severe Major Depressive Disorder by Reducing Negative Future-Oriented Mental Imagery

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06454695
• Other study ID #: 2023.0973
• Secondary ID: NL85551.018.23
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: November 1, 2025

Study information

• Verified date: June 2024
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Evi-Anne van Dis, PhD
• Phone: +31 630485261
• Email: profitstudie[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with major depressive disorder (MDD) often do not sufficiently benefit from treatment. That is, around 50% of patients with MDD do not respond to treatment and 20-30% only achieve partial remission. Future-oriented negative mental imagery (e.g., mental images of suicide or own funeral) is likely an important maintaining factor of depression and initial studies in depression indicate that targeting mental imagery with 'imagery rescripting' could be a promising therapeutic technique to reduces depressive symptomatology by targeting these images directly that elicits strong affects/emotions and depressive symptomatology. Before testing the (cost)effectiveness of future-oriented imagery rescripting to treatment as usual (TAU), a pilot study is needed to examine 1) the acceptability of the intervention, 2) the feasibility of the study, and 3) the variance of effect on reducing depressive symptomatology that can serve as estimate of the sample size for a follow-up randomized controlled trial (RCT). A multicenter pilot RCT with a mixed factorial design with three time points (i.e., baseline, post-treatment, and follow-up of 3 months) will test 50 patients with MDD who will be randomly allocated to future-oriented imagery rescripting plus TAU or TAU only. The sample consists of adult patients of 18 years or older with an MDD diagnosis. All patients in this pilot study receive TAU, which involves a combination of pharmacological and psychological interventions. Half of the patients will also receive 3-5 sessions of future-oriented imagery rescripting (ImRes). In each ImRes session, patients identify an image of a autobiographic catastrophic future event (e.g., catastrophic images of future suicide or the loss of work or a loved one). They are subsequently asked to "rescript" this image into a more benign one. The primary aim of this pilot study is to determine the acceptability of the intervention. The secondary aims are to elucidate factors that may facilitate or hinder the feasibility of the follow-up RCT (e.g., recruitment process) and to estimate the variance of the effect on reduction of depressive symptomatology, which informs the sample size calculation of the follow-up RCT. To study acceptability, the investigators assess depressive symptoms (BDI-II and BADS) and treatment satisfaction (SRS and CSQ-8). To measure feasibility, the investigators will assess recruitment/admission ratio, dropout and (serious) adverse events. Finally, to estimate the variance of effects, group effects on the BDI-II will be tested at post-treatment and follow-up (corrected for baseline). Imagery rescripting on negative memories has already proven effective and safe in MDD patients. There is no known major risk associated with study participation. Patient burden comprises an online or phone-based screening interview of maximum 60 minutes and several questionnaires. Participants receive a reimbursement of €25,- after study completion (i.e., after follow-up assessment). The project will contribute to improving the care for patients with MDD. If the results show that the intervention is feasible and acceptable, this pilot study will inform the setup of the main RCT on the (cost)effectiveness of the intervention (ZonMW).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: November 1, 2025
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Aged 18 years or older;
• Meet DSM-5 criteria for major depressive disorder;
• Presence of 1-3 negative future-oriented mental images, which cause distress;
• Be able to understand questionnaires and study information letter;
• In case of medication use: are stable on medication for six weeks or longer.

Exclusion Criteria:

• Current or history of psychotic disorder;
• Current or history of bipolar disorder;
• Severe cognitive impairment (e.g., mental retardation) as evidenced by educational records, parental report and/or clinical impression;
• Current EMDR or imagery rescripting therapy;
• Other circumstances that might affect participation (e.g., severe medical disorder, relocation).

Related Conditions & MeSH terms

• Cognitive Behavioral Therapy
• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Behavioral:
• Future-oriented imagery rescripting
In this pilot study, in the screening phase, negative or catastrophic future-oriented images will be explored for all patients, including ratings of distress. The future-oriented imagery rescripting consists of 3-5 sessions; each image will be treated in one session, starting with the image that causes highest distress. The protocol is largely based on Hackmann (1998), with minor adaptations from other protocols.

Other:
• Treatment as Usual
Psychotherapy and/or medication

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC (location AMC)	Amsterdam	Noord-Holland

Sponsors (7)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	Depressie Vereniging (patient association), GGZ Eindhoven (participating site), Mental Care Group (i.e., HSK group and Mentaal Beter; participating sites), MIND (civil society organization), Praktijk V (participating site), ZonMw (funding)

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Structured Clinical Interview for DSM-5	Structured Clinical Interview for DSM-5; SCID-5 - Dutch version: sections on depressive disorders, psychotic disorder, anxiety disorders, substance use disorder and posttraumatic stress disorder	Screening
Other	Positive and Negative Affect Schedule	Positive and Negative Affect Schedule (PANAS) for affect, consisting of 20 questions with scores between 1-5. For the total positive score, a higher score indicates more of a positive affect. For the total negative score, a lower score indicates less of a negative affect.	From baseline to the end of the study at follow-up (total of 18 weeks).
Other	5-level EQ-5D	5-level EQ-5D (EQ-5D-5L) for quality of life, consisting of 5 questions with scores between 1-5 whereby a higher score indicates a worse outcome.	From baseline to the end of the study at follow-up (total of 18 weeks).
Other	Generalized Anxiety Disorder	Generalized Anxiety Disorder questionnaire (GAD-7) for anxiety, consisting of 7 questions with scores between 0-3 whereby a higher score indicates a higher burden.	From baseline to the end of the study at follow-up (total of 18 weeks).
Other	Rating of mental images	Rating of mental images on emotions, vividness, uncontrollability, distress and core belief, using a visual analogue scale, ranging from 0-100 whereby a higher score indicates a high level of presence.	From baseline to the end of the study at follow-up (total of 18 weeks).
Other	Prospective Imagery Task	Prospective imagery task (PIT) for vivedness and likelihood of mental images, consisting of 20 questions with scores between 0-5, whereby a higher score indicates a higher possibility.	From baseline to the end of the study at follow-up (total of 18 weeks).
Other	Monitoring of Treatment as Usual	Monitoring of 'Treatment as Usual' (TAU) via their therapist. "Which therapy has the patient received (including medication + dose; possible in-patient treatment)?"	From baseline to the end of the study at follow-up (total of 18 weeks).
Primary	Beck Depression Inventory (Acceptability)	Beck Depression Inventory (BDI-II) for depressive symptoms, consisting of 21 questions with scores between 0-3 whereby a higher score indicates a worse outcome.	From baseline to the end of the study at follow-up (total of 18 weeks).
Primary	Behavioral Activation for Depression Scale (Acceptability)	Behavioral Activation for Depression Scale (BADS-NL) for depressive symptoms, consisting of 25 questions with scores between 0-6 whereby a higher score indicates a worse outcome.	From baseline to the end of the study at follow-up (total of 18 weeks).
Primary	Session Rating Scale (Treatment satisfaction)	Session Rating Scale (SRS) is filled in during the intervention, consisting of 4 visual analogue scales ranging between 0-100.	During treatment intervention (total of 5 weeks)
Primary	Client satisfaction Questionnaire (treatment satisfaction)	Client Satisfaction Questionnaire (CSQ-8), consisting of 8 questions whereby the answers ranged from totally disagree to totally agree	After the study intervention and at follow-up
Secondary	Recruitment/admission ratio (Feasibility)	Recruitment/admission ratio.	From enrollment to the end of the study at follow-up (total of 18 weeks).
Secondary	Dropout (Feasibility)	Dropout.	From enrollment to the end of the study at follow-up (total of 18 weeks).
Secondary	(serious) adverse events (Feasibility)	(serious) adverse events.	From enrollment to the end of the study at follow-up (total of 18 weeks).
Secondary	Variance of effect	Group effects on the Beck Depression Inventory (BDI-II) will be tested at post-treatment and 3 months follow-up (corrected for baseline).	From enrollment to the end of the study at follow-up (total of 18 weeks).