Clinical trial NCT03517592: EMDR Versus Treatment As Usual in Patients With Substance Use Disorder
Official title: A Multicenter Phase II Rater-Blinded Randomized Controlled Trial to Compare the Effectiveness of Eye Movement Desensitization Reprocessing Therapy vs. Treatment as Usual in Patients With Substance Use Disorder and History of Psychological Trauma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Substance Use Disorders
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
First posted: 2018-05-07
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective of this project is to test whether EMDR therapy is effective in reducing substance use and improving clinical and trauma-related symptoms in SUD patients with a history of psychological trauma.

Detailed description: Background:

Substance use disorders (SUD) represent an important social and public health problem due to their negative consequences in terms of delinquency, family disintegration, academic and occupational disengagement, mental illness, transmission of infectious diseases, intoxication and mortality rates. As with other mental disorders, the evolution of this disorder depends on many biological and sociodemographic variables, such as the age of onset of consumption, access to drugs, one's living environment, race, and the presence of stressors. Of all these variables, adverse events are being increasingly investigated, due to the strong negative impact they have on the onset, course and prognosis of psychiatric disorders, especially when psychological trauma is present. Traumatic events, especially in childhood or adolescence, are considered to be a robust risk factor for developing post-traumatic stress disorder (PTSD), with or without further comorbid severe mental disorders such as depression, bipolar disorder, psychosis or SUD. A recent meta-analysis published in the Lancet found multiple adverse childhood events to be a significant risk factor for problematic alcohol and substance use, highlighting the impact of adverse childhood events even when not associated with a diagnosis of PTSD. Although there is currently no available data about the prevalence of traumatic events in SUD patients population, it is estimated that is likely high presumed to be high. The results of different studies estimate that the prevalence of PTSD in inpatients with SUD to ranges from 25% -51%, which is two to four times higher than the prevalence range found in the general population (1.3% -12.3%). In addition, evidence suggests that PTSD and traumatic events are correlated with addiction severity, with a worse disease prognosis, with a greater number of hospitalizations, with a poorer response to treatment, with shorter periods of abstinence and with greater craving. Thus, an integral model with an individualized treatment plan is indicated in SUD, including psychological trauma as a specific objective to address.

A possible candidate for this is Eye Movement Desensitization and Reprocessing (EMDR) therapy, which is considered to be a first line treatment for PTSD, being recommended by different international bodies, such as the American Psychiatric Association (APA) and World Health Organization (WHO). EMDR is a psychotherapeutic approach designed to alleviate the distress associated with traumatic memories, facilitating the access to and processing of traumatic memories and other adverse life experiences and bringing these to an adaptive resolution using standardized protocols and elements of cognitive behavioral, interpersonal, and body-centered therapies in conjunction with bilateral stimulation (e.g. horizontal eye movements from side to side). In recent years, the use of EMDR has increased exponentially in clinical practice due its effectiveness and safety and that has resulted in investigations in additional populations beyond PTSD, such as in those with depression, anxiety, chronic pain, bipolar disorder, or psychosis. Of note, three small randomized controlled trials (RCT) of EMDR versus Treatment As Usual (TAU) have also been performed in patients with SUD. The results suggest that EMDR, compared to the control group, significantly improved craving, depression, anxiety, self-esteem and dissociative symptoms, but samples were small. A large scale RCT is currently underway, which aims to determine the efficacy of EMDR in reducing PTSD symptoms in an inpatient sample with comorbid PTSD or subthreshold PTSD and SUD. In view of the above, we consider that a further large RCT of EMDR in the treatment of psychological trauma in outpatients with SUD, including psychological trauma related to adverse events not covered by DSM-V diagnostic criteria, is crucial and clinically necessary due to the negative impact it has on the course and prognosis of these illnesses, and in order to confirm or reject prior first positive evidence. Our study is also important in including patients with dual pathology and measuring impact on psychopathological symptoms, which will help facilitate the application of EMDR in a real world setting if it is shown to be efficacious.

Design:

This is a single-blind RCT with two parallel branches, EMDR and TAU, in patients diagnosed with SUD who have suffered from comorbid psychological trauma. The patients will be matched by center, age, sex and diagnosis. One group will consist of TAU + 20 individual EMDR sessions, 60 minutes each, during 6 months, the other group will receive TAU only. Patients will be evaluated at baseline, at 3 months, post-treatment at 6 months and at 12 months as follow-up.

Clinical and diagnostic variables:

1. Clinical diagnosis of the participants will employ DSM-V criteria for SUD based on clinical interview (Psychiatric Research Interview for Substance and Mental Disorders; PRISM). The investigators also will use the Mini-International Neuropsychiatric Interview for the detection of the most frequent comorbid psychiatric diagnoses in substance abusers.
2. Clinical Severity of the participants will be assessed by different instruments:

   1. Hamilton Depression Rating Scale: It has been designed to assess the severity and changes of depressive symptoms.
   2. Young Mania Rating Scale:It is a hetero-administered scale composed of 11 items aimed at quantifying the severity of manic and hypo manic episodes.
   3. Brief Psychiatric Rating Scale: It is a hetero-administered scale composed of 18 items measuring psychopathological changes. It includes anxious, affective and psychotic symptoms with each symptom rated on a severity scale of 1-7.

The consumption of SUD is quantified using the following tools:

1. Timeline Followback Questionnaire.
2. Severity of Dependence Scale.
3. Visual Analog Scale.

Trauma symptoms and overall functioning will be evaluated by the following instruments:

1. Childhood Trauma Questionnaire.
2. The Holmes-Rahe Life Stress Inventory.
3. Impact of Event Scale - Revised.
4. Subjective Unit of Discomfort.
5. Dissociative Experiences Scale.
6. Functioning Assessment Short Test: This is a brief instrument to evaluate performance in six different areas of functioning, such as autonomy, occupational functioning, cognitive functioning, finances, relationships and leisure.

The investigators have included a Spanish validated version of all these instruments.

Statistical analysis:

1. Computation of sample size: The study aims to assess the efficacy of EMDR therapy compared with TAU for patients with SUD focused on reduction of substance use, reduction of symptoms associated with craving, associated symptoms of anxiety and depression and functioning. The sample size has been calculated based on a comparison of a normal variable (pre-post reduction) between two independent groups (treated and untreated) using the statistical package R (http: //www.r-project.org/), using an alpha = 0.005 instead of 0.05 to allow correction for multiple comparisons. The number of patients required to detect major effects (d = 0.8) with a statistical power of 80% and alpha = 0.005 is n = 60 per intervention group (two groups, n total = 120). Assuming a loss percentage of approximately 10-15% of the patients in the study, it would be necessary to recruit approximately 132 patients, 66 for each intervention branch.
2. Analysis of the main variables: The distribution of socio-demographic and clinical characteristics between groups in the baseline state will be analyzed by means of descriptive statistics. The continuous variables with a normal distribution will be analyzed with the Analysis of Multivariate Variation (ANOVA). The change in clinical and functional variables with regard to baseline evaluation at strategic points of the intervention will be analyzed using linear models of mixed effects and repeated measures, including fixed factors of time, treatment conditions and their interaction, and the random center factor. The differences between groups, for the categorical variables and main clinics, will be analyzed by adding covariates to the models. Those covariates that are statistically significant may be added in the same model to determine which covariates are best predictors of the response. The index of the size of the effect (index g of Hedges or r of Pearson) of each of the analysis carried out will be estimated. It will be corrected for multiple comparisons. The statistical software used for the analysis will be the latest available version of the SPSS (version 23).
3. Analysis of clinical efficacy: For the main statistical analysis, the population will be used for intent to treat (ITT). The "Last Observation Carried Forward" (LOCF) method will be used as a measure of minimization of lost ones.

Eligibility criteria: Inclusion Criteria:

* age between 18 and 65 years
* outpatients
* presence of one or more traumatic events, which causes currently trauma associated symptoms (Scale of the impact of the event-reviewed, IES-R\> 0) and subjective Disability Unit (SUD)\>5)

Exclusion Criteria:

* presence of organic brain diseases
* presence of suicidal ideas
* having received a trauma focused therapy in the last 2 years

Primary outcomes:
measure: Reduction in severity of consumption
timeFrame: Changes from baseline to visits at 3, 6 and 12 months.
measure: Reduction in level of consumption
timeFrame: Changes from baseline to visits at 3, 6 and 12 months.
measure: Reduction in the number of relapses
timeFrame: Change of relapses from baseline to visits at 3, 6 and 12 months.
measure: Reduction of (hypo) manic symptoms associated with a comorbid psychiatric disorder
timeFrame: Changes from baseline to visits at 6 and 12 months.
measure: Reduction of general psychopathological symptoms associated with psychiatric comorbidity
timeFrame: Change from baseline to visits at 6 and 12 months.
measure: Reduction in depressive symptoms associated with a comorbid psychiatric disorder
timeFrame: Changes from baseline to visits at 6 and 12 months.
Secondary outcomes:
measure: Improvement of global functioning
timeFrame: Changes from baseline to visits at 6 and 12 months.
measure: Detection of Childhood life traumatic events
timeFrame: Childhood. It is administered only during the baseline visit.
measure: Detection of traumatic events in the last year
timeFrame: The last year. It is administered only during the baseline visit.
measure: Making a PTSD diagnosis
timeFrame: Changes from baseline to visits at 6 and 12 months.
measure: Assessment of the severity of trauma-related symptoms.
timeFrame: The previous 7 days. Changes from baseline to visits at 6 and 12 months.
measure: Detection of dissociative symptoms
timeFrame: Changes from baseline to visits at 6 and 12 months.
Other outcomes:
Locations:
city: Sant Boi De Llobregat
country: Spain
facility: Germanas Hospitalarias Benito Menni
state: Barcelona
city: Barcelona
country: Spain
facility: Parc de Salut Mar
Study officials:
affiliation: Parc de Salut Mar
name: Benedikt L Amann, PhD, MD
role: PRINCIPAL_INVESTIGATOR
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