RCT Comparing EMDR and CBT for Treatment of Resistant Depression

Multicenter RCT Comparing EMDR and CBT Efficacy for Treatmen of Resistant Depression

Depression is one of the most common invalidating mental disorders, ranked by World Health Organization as the single largest contributor to global disability. Current recommended treatments for depression include antidepressant medication and according to guidelines, Cognitive Behavioral Therapy (CBT) and Interpersonal Therapy (IPT). Despite encouraging preliminary results (e.g., Matthijssen et al., 2020), Eye Movement Desensitization and Reprocessing (EMDR) therapy is not yet recognized as an effective therapy for depression by APA and NICE. The project aims to conduct a large multisite study that addresses the shortcomings of previous efficacy research on EMDR for depression. The primary aim is to evaluate the effectiveness of EMDR therapy in reducing depressive symptoms in adults with major depression as compared to CBT. Secondary aims of the study are the effectiveness of EMDR, as compared to CBT and TAU, in improving anxiety, and other symptoms. It is hypothesized that EMDR is not inferior to CBT.

Study Overview

• Status: Recruiting
• Conditions: Depression; Heart Rate Variability; Functional Magnetic Resonance Imaging; Cognitive Behavioral Therapy; Eye Movement Desensitization and Reprocessing; Neurobiological Processing; High Definition Electroencefalography
• Intervention / Treatment: Behavioral: EMDR; Behavioral: CBT

Detailed Description

The study is a multicenter clinical randomized controlled trial, conducted in Italy, USA and UK that will assess the effectiveness of EMDR therapy compared to CBT and TAU. Patients will be recruited at four clinical centers: Turin and Rome in Italy, and Kansas City in USA. The study protocol was approved by the local research ethics committee in each of the countries where the intervention is implemented.

• Study Type: Interventional
• Enrollment (Anticipated): 128
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Luca Ostacoli, Associate Professor; Phone Number: 3335613155; Email: luca.ostacoli@unito.it

Study Locations

• Italy
  • Torino, Italy, 10126
    • Recruiting
    • AOU Città della Salute e della Scienza di Torino
    • Contact: Luca Ostacoli, Assistant Professor; Phone Number: 3335613155; Email: luca.ostacoli@unito.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. a diagnosis of Major Depressive Disorder, single episode or recurrent, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5);
2. a score of at least 20 on Beck's Depression Inventory-II (BDI-II);
3. having received ADM treatment with a stable dose for at least six weeks and maintained stable during treatment;
4. legal capacity to consent to the treatment.

Exclusion Criteria:

1. diagnosis of current PTSD (assessed with MINI-Plus and the International Trauma Questionnaire - ITQ, Cloitre et al., 2018);
2. diagnosis of complex PTSD (assessed with the ITQ);
3. history of psychotic symptoms or schizophrenia;
4. bipolar disorder or dementia;
5. cluster A and B severe personality disorders;
6. dissociative symptoms (DES-B score >2);
7. any substance-related abuse or dependence disorder (except those involving nicotine) in the 6 months prior to the study;
8. a serious, unstable medical condition;
9. a severely unstable social and economic condition (e.g. no fixed abode; job loss without any other source of income);
10. being pregnant;
11. acute suicidality that needs hospitalization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eye Movement Desensitization and Reprocessing; The DeprEND manualized protocol (Hofmann, Ostacoli, et al., 2015) is based on the eight-phase protocol by Shapiro (2001) that was adapted for the treatment of depression by the European Depression EMDR Network and used in previous studies (Hase et al., 2015; Hofmann et al., 2014; Ostacoli et al., 2018). EMDR targets will be selected using the Adaptive Information Processing model that looks for stressful events linked with depression. The DeprEnd Fidelity Rating Scale will be used to assess treatment fidelity. The scale will be completed by trained EMDR therapists who will listen to the audio recordings of the sessions. In each centre, EMDR is provided by psychotherapists specialized in Level II EMDR and with a minimum of three years of experience in treating patients with depression. They receive extensive training and supervision in the manualized protocol established for the study, from a certified senior EMDR instructor.	Behavioral: EMDR; Treatments will be independent and blinded to the clinical psychologists conducting the clinical assessments. EMDR and CBT treatments will be provided for 16 weeks, each comprising 16 weekly individual sessions. Interventions will be conducted according to published treatment manuals. All treatment sessions will be video recorded for fidelity rating and supervision. As a safety criterion, if severe worsening of symptoms is observed, patients are withdrawn from their assigned treatment arm.; Other Names: Eye Movement Desensitization and Reprocessing
Active Comparator: Cognitive Behavioral Therapy; Treatment protocol is based on the principles described by Beck (Beck et al., 1979) will be utilized. The treatment includes behavioral activation and cognitive restructuring with homework assignments. In each centre, CBT treatment is performed by psychotherapists with certified training in CBT techniques and a minimum of three years of experience in treating patients with depression. They receive regular CBT supervision to ensure that the quality of their CBT treatment was maintained.	Behavioral: CBT; Treatments will be independent and blinded to the clinical psychologists conducting the clinical assessments. EMDR and CBT treatments will be provided for 16 weeks, each comprising 16 weekly individual sessions. Interventions will be conducted according to published treatment manuals. All treatment sessions will be video recorded for fidelity rating and supervision. As a safety criterion, if severe worsening of symptoms is observed, patients are withdrawn from their assigned treatment arm.; Other Names: Cognitive Behavioral Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in depressive symptoms	Beck Depression Inventory II (BDI-II)	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup).
changes in depressive symptoms	Hamilton Depression Rating Scale (HDRS)	week 0, week 16, week 40
changes in cognitive component of depressive syndrome	Beck Hopelessness Scale (BHS)	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
changes in HD-EEG	HD-EEG in resting state phase and a second phase with a task	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
changes in fMRI	fMRI in resting state phase and a second phase with a task	month 0 (T0)
changes in HRV	HRV detection during hdEEG assessment	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
psychiatric diagnosis	Structured Clinical Interview for DSM-5 (SCID-5)	month 0 (T0)
changing in depressive symptoms	Patient Health Questionnaire-9 (PHQ-9)	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup) and every week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
addressing potentially traumatizing events	Traumatic Experience Checklist (TEC)	month 0 (T0)
assessing childhood trauma	Childhood Trauma Questionnaire (CTQ)	month 0 (T0)
evaluating the quality of relationships	Relationship Questionnaire (RQ)	month 0 (T0)
changing in dissociative symptoms	Brief Dissociative Experiences Scale (DES-B)	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
changing in autonomic symptoms	Composite Autonomic Symptom Score (COMPASS-31)	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
changing in the emotional regulation	Difficulties in Emotion Regulation Scale (DERS)	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
changing in the dimensions of the emotional style	Emotional Style Questionnaire (ESQ)	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
changing in quality of sleep, in particular insomnia	Insomnia Severity Index (ISI)	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
changing in physical activity habits	International Physical Activity Questionnaire Short Form (IPAQ-SF)	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
changing in post-traumatic symptoms	International Trauma Questionnaire	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
changing in suicidal thinking	Paykel Suicide Scale	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
changing in stress	Perceived Stress Scale (PSS)	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
changing in post-traumatic stress symptoms	PTSD Checklist for DSM-5 (PCL-5)	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup)
assessing disability and functional impairment as a result of treatment	Sheehan Disability Scale for Treatment Induced Impairment (SDS-T)	1 month time frame
changing in anxiety symptoms	General Anxiety Disorder-7 (GAD-7)	month 0 (T0, baseline), month 4 (T1, post-treatment), month 10 (T2, followup), month 22 (T3, followup) and every week

Collaborators and Investigators

• Sponsor: University of Turin, Italy
• Collaborators: EMDR Europe

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2019
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: March 27, 2019
• First Submitted That Met QC Criteria: May 30, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Actual): March 14, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: trauma; depression; psychotherapy; Cognitive Behavioral Therapy; neurobiology of emotions; Eye Movement Desensitization and Reprocessing
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: EMDRvsCBT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No