EMDR vs Supportive Therapy in Relapse Prevention in Traumatized Bipolar Patients
Condition: Bipolar Disorder
MeSH terms: Recurrence; Bipolar Disorder
Study type: Interventional

Summary: 
      The purpose of this study is to determine whether EMDR (vs supportive therapy) is effective
      in relapse prevention over an observational period of 2 years in bipolar patients with a
      history of traumatic events.
    

Detailed description: 
      Background:

      The intervention strategies available for bipolar disorder are essentially pharmacotherapy
      and psychosocial interventions such as cognitive behavioral therapy, psychoeducation, and
      interpersonal and family therapy. However, despite the everyday use in clinical practice of
      both types of intervention, almost 70% of patients with bipolar disorder suffer an affective
      relapse within two years. Although the origin of this is multi-causal, an emerging research
      topic is the association of bipolar disorder with posttraumatic stress disorder (PTSD). Data
      from the STEP-BD study showed a prevalence of 20% of PTSD in a sample of 3158 bipolar
      patients, a rate almost three times higher than the prevalence of PTSD in the general
      population. This comorbidity has important clinical implications as the traumatized bipolar
      patients suffer from more rapid cycling, more suicide attempts, more substance abuse, have
      lower quality of life and more (hypo) manic and depressive symptoms than bipolar patients
      without PTSD. The results are similar in populations with severe mental illness and a history
      of trauma (not necessarily diagnosis of PTSD). These populations have more affective
      episodes, more psychiatric symptoms, increased risk of suicide, more frequency of risk sexual
      behaviors, more admissions to psychiatric hospitals and in overall, a greater risk of being
      re-traumatized.

      The strength of the evidence supporting the clinically relevant effects of PTSD and/or
      history of trauma in bipolar disorder contrasts with a surprising lack of trials aimed at
      treating patients who have experienced traumatic events. One form of treatment that is being
      increasingly used in PTSD therapy is Eye Movement Desensitization and Reprocessing (EMDR).
      This integrative psychotherapeutical approach uses standardized protocols and elements of
      cognitive-behavioral, interpersonal, and body-centered therapies in conjunction with dual
      stimulation (e.g. horizontal eye movements from side to side). The results of two independent
      meta-analyzes have shown that the EMDR therapy is as effective in the treatment of PTSD
      symptoms as cognitive behavioral therapy. The treatment with EMDR has also been tested
      successfully versus exposition therapy and waiting list in a large randomized controlled
      trial in patients with psychosis and PTSD. Their results showed a significant reduction of
      trauma scores in both intervention in comparison to the waiting list and both intervention
      were regarded as safe with respect to exacerbation of psychotic symptoms. Our group carried
      out the first randomized controlled pilot study of EMDR in bipolar traumatized patients with
      subsyndromal symptomatology. Our results showed that the EMDR intervention not only reduced
      the symptoms associated with trauma in the patients, but also had beneficial effects on the
      symptoms of subsyndromal mood. Following the results this study, our research group has
      developed a specific and comprehensive EMDR protocol for bipolar patients with a history of
      trauma. This protocol consists of a comprehensive survey of traumatic events, the
      intervention and processing of these events according to the Shapiro standard protocol and 5
      sub-protocols directed to (a) enhance treatment adherence, (b) increase insight, (c) treat
      prodromal symptoms, (d) work on the de-idealization of manic symptoms and (e) provide mental
      stabilization.

      Aims and hypotheses:

      The main objective of this study is to examine if EMDR therapy with protocols specific to
      bipolar patients with a history of traumatic events can act as a mood stabilizer. This would
      result in less affective relapses and better overall and cognitive functioning after 6 months
      of therapy in the group that received EMDR submit compared with the ST group. Other related
      aims of this project are to expand the available options for psychosocial intervention in
      bipolar disorder, to demonstrate that the EMDR therapy is a safe and effective tool in
      traumatized bipolar patients and that treatment with EMDR lead to an improvement in the
      course and prognosis of the disease.

      Hypotheses:

        1. The EMDR group will show less affective relapses at 12 and 24 months follow-up compared
           to the ST group.

        2. Patients in the EMDR group will show less affective symptoms compared to the ST group at
           evaluations at 6, 12 and 24 months.

        3. Patients in the EMDR group will show better cognition and functioning compared to the ST
           group at evaluations at 6, 12 and 24 months.

      Design:

      Single-blind randomized clinical trial (1:1) with two parallel branches, stratified by center
      for age, sex, number of previous affective episodes and cognitive state. The preventive
      effect of two psychological interventions, individual EMDR therapy or ST plus pharmacological
      treatment in patients diagnosed with bipolar I and II disorder with history of traumatic
      events, in a current affective phase of euthymia or subsyndromal symptoms will be evaluated.
      The comparative clinical effect in both branches of intervention will be assessed at five
      time points. There will be a pre-intervention baseline assessment, a post-intervention
      assessment at 6 months and follow-up evaluations at 12, 18 and 24 months.

      Clinical and diagnostic variables:

        1. Clinical diagnosis of the participants will employ DSM-IV-TR criteria.

        2. Clinical Severity of the participants will be assessed by different instruments:

             1. Bipolar Depression Rating Scale (BDRS): The BDRS is the most up-to-date and
                appropriate tool to assess depressive and mixed symptoms in bipolar patients. Our
                group has been involved in the translation and validation of the scale into
                Spanish.

             2. Young Mania Rating Scale (YMRS) which is validated in Spanish: YMRS is a
                hetero-administered scale of composed of 11 items aimed at quantifying the severity
                of manic and hypo manic episodes.

             3. Clinical Global Impression Scale modified for bipolar disorder (CGI-BP-M), Spanish
                validation: The CGI-BP-M scale consists of 3 subscales; the first two assess the
                severity of acute symptoms of mania and depression, and the third evaluates the
                longitudinal severity of the disease. Each subscale has seven sub-categories with
                scores from 1 to 7 rating the severity of the disorder as normal, low, mild,
                moderate, marked, severe or very severe.

           Other clinical variables will be collected via the medical history of the patients and
           using a specific CRF for the study such as age of onset of the disorder, number of
           relapses, number of previous episodes, history and number of suicide attempts and
           pharmacological variables such as the number, type and dose of drugs.

        3. Trauma symptoms, cognitive profiles and overall functioning will be evaluated by the
           following instruments:

             1. Clinician-Administered PTSD Scale (CAPS) which is validated in Spanish.

             2. Impact of Event Scale Revised (IES-R).

             3. Distressing Event Questionnaire.

             4. Traumatic Life Events Questionnaire.

           c. Functioning Assessment Short Test (FAST). d. Screen for Cognitive Impairment in
           Psychiatry (SCIP) which is validated in Spanish.

           e. Screen for social cognition, emotional intelligence: Mayer-Salovery-Caruso Emotional
           Intelligence Test.

           Statistical analysis:

             1. Computation of sample size The study will assess the relative efficacy of a
                specific EMDR intervention protocol versus Supportive Therapy (ST) in the clinical
                stabilization (decrease in the number of relapses) of traumatized bipolar patients.
                For this reason the number of affective episodes after treatment with a follow up
                of 24 months will be used as the dependent variable of the study. The sample size
                computation is based on a recent study comparing CBT versus ST with 24 months
                follow up on the relapse in bipolar patients. The calculation of the sample size
                was based on a survival analysis using the statistical package "powerSurvEpi" for R
                (http://www.r-project.org/) using an alpha = 0.005 instead of 0.05 for allow
                correction for multiple comparisons. The number of patients required to detect a
                hazard ratio = 2 in a cox regression with a statistical power of 80% and alpha =
                0.005 is n = 36 per intervention group (two groups, EMDR and ST, equals to a total
                n = 72). A sample of this size should show clinically relevant differences.
                Assuming a percentage of drop-outs of about 10-15% of the participants it would be
                necessary to recruit approximately 82 patients, 41 allocated in each intervention
                arm.

             2. Analysis of the main variables The baseline distribution of socio-demographic and
                clinical characteristics between the groups will be analyzed using descriptive
                statistics. Continuous variables with a normal distribution will be analyzed with
                Multivariate Analysis of Variance (MANOVA). The main hypothesis of survival time
                (in weeks) will be analyzed using Kaplan-Meier curves with tests of significance
                tests based on log-rank test. The change in baseline clinical variables compared to
                baseline at strategic time points of the trial will be analyzed by repeated
                measures ANOVA factor in for time, treatment conditions and their interaction. The
                Wilcoxon test will be used in cases that do not meet the assumptions of normality.
                Between groups differences in main categorical and clinical variables will be
                analyzed using the Chi-squared test. Those variables that are statistically
                significant will be used as covariates in a linear logistic regression of factors
                associated with the magnitude of the effect in order to determine which factors are
                better predictors of performance. For each of the analyses the effect size index
                (Hedges g index or Pearson r index) will be estimated. The latest version of the
                SPSS software (v. 18, 20) will be used to carry out all the statistical analysis.

             3. Analysis of clinical efficacy The mains statistical analysis will employ an
                intention to treat (ITT) approach to provide unbiased comparisons among the
                treatment groups. The "Last Observation Carried Forward" approach (LOCF) will be
                employed as a measure of minimizing losses.
    

Intervention name(s): EMDR therapy; Supportive Therapy
Intervention type(s): Behavioral; Behavioral
Intervention description(s): EMDR: We designed a specific EMDR Bipolar Protocol which consists of a detailed interview with respect to traumatic events, the treatment of those with the EMDR standard protocol, and five new specific bipolar adapted EMDR protocols focusing on adherence, insight, de-idealisation of manic symptoms, prodromal symptoms and moodstabilization.; Supportive therapy: Therapists adopt a client-centred focus, meaning that whatever problems the patient presents will be dealt with by providing emotional support and general advise. If no specific topic is mentioned by the patient, information about bipolar disorder and medication will be delivered by the therapist without referring to written or any other material.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Bipolar Disorder; Traumatic event; Eye Movement Desensitization Reprocessing; Supportive therapy; Relapse prevention