EMDR in Adolescents With Bipolar Disorder and History of Trauma

EMDR Therapy in Relapse Prevention in Mood Episodes in Adolescents With Bipolar Disorder and History of Trauma: A Randomized Clinical Trial

In this research, EMDR protocol model specific for bipolar patients with a history of trauma, developed by Benedikt Ahmann et al (2017), who applies EMDR in adults with Bipolar Disorder (BD) and history of trauma will be adapted for adolescents. This protocol consists of a detailed survey of traumatic events, intervention and processing of these events according to the standard protocol developed by Shapiro.

The main hypothesis is that the use of EMDR in adolescents with BD and history of trauma, as a complement to the pharmacological treatment (Usual Treatment), would have beneficial effects in the course of the disease. Thus, the overall objective of this study is to examine whether EMDR therapy in adolescents with BD and history of traumatic events can reduce affective relapses within a 12-month period. In addition, improvement in biological markers related to BD is expected to be found when compared to the Usual Treatment. It is also expected that patients treated with EMDR will present a better neurocognitive functioning profile, assessed by means of a neuropsychological evaluation battery before and after the intervention, since recent studies show that the profile of humoral dysregulation, impulsiveness, difficulty in dealing with frustrations and social feedback in children and adolescents with BD is associated with poor cognitive control and executive function deficits.

Study Overview

• Status: Unknown
• Conditions: Bipolar Disorder
• Intervention / Treatment: Other: Eye Movement Desensitization and Reprocessing (EMDR) Therapy; Other: Treatment as Usual

Detailed Description

This will be a randomized controlled trial. Participants will be assigned to Eye Movement Desensitization and Reprocessing (EMDR) Therapy or Treatment as Usual (TAU) through block randomization. This process will be done using the program available at www. randomization.com.

In this study, EMDR Therapy will be applied in adolescents with BD and compared to the Usual Treatment. The neuropsychological profile of the patients will be evaluated before and after the interventions. In addition, the collection of the biological markers related to BD will be done by measuring the levels of salivary cortisol and serum levels of C-reactive protein (CRP), Brain Derived Neurotrophic Factor (BDNF), Interleukin (IL) - 1β, IL - 2, IL - 4, IL - 6, IL - 10, Interferon gamma (IFN-γ) and Tumor Necrosis Factor alpha(TNF-α) in these patients, since a study proposing the use of serological biomarkers for BD diagnosis concluded that the use of a single biomarker would be of little use and a combination of several biomarkers would be necessary.

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-007
      • Recruiting
      • Centro de Pesquisas Clínicas do Hospital de Clínicas de Porto Alegre
      • Contact: Andrea Rambo; Phone Number: +555133598943; Email: l-cpc-recepcao@hcpa.edu.br
      • Contact: Tatiana L Peruzzolo; Phone Number: +555133598943; Email: tperuzzolo_pos@hcpa.edu.br
      • Principal Investigator: Ives C Passos, PhD
      • Sub-Investigator: Tatiana L Peruzzolo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age between 12 and 17 years and 11 months;
2. current clinical state of euthymia (patient stable or euthymic) after clinical evaluation, defined as the presence of clinical remission (CDRS ≤ 40, YMRS ≤ 12.5 and CGAS (Children's Global Assessment Scale) ≥ 51), being the presence of subsyndromic symptoms (YMRS> 8 and <14) admissible;

3. Presence of one or more distressing traumatic events, assessed by:

   1. Trauma subscale of the Post Traumatic Stress Disorder Questionnaire from the Schedule for Affective Disorders and Schizophrenia for School Aged Children Present and Lifetime Version (K-SADS-PL) , with frequency> 1;
   2. Holmes Rahes Stress Inventory for non-adults (H-RLSI) with frequency> 1;
   3. Children Revised Impact of Event Scale (CRIES)> 0;
   4. Childhood Trauma Questionnaire (CTQ)> 0; and
   5. at least 5 points in the disturbance assessment by the Subjective Units of Disturbance (SUDS) scale.

Exclusion Criteria:

1. substance abuse / dependence within 3 months prior to participation;
2. neurological disease or history of brain trauma;
3. autism;
4. Intelligence Quotient <70;
5. suicidal or homicidal ideation;
6. prior involvement in trauma-focused therapy;
7. psychotherapy during the study and months of follow-up, and;
8. a score greater than 25 on the Adolescent Dissociative Experience Scale, since the presence of massive dissociation requires different and more extensive treatment protocols.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EMDR Therapy + TAU; Patients will be submitted to 20 individual sessions of Eye Movement Desensitization and Reprocessing (EMDR) Therapy of 60 minutes each, combined to the Treatment as usual (TAU). It's an eight-step process aimed at the traumatic events, also used to address current situations that evoke emotional disturbances so they do not trigger more symptomatic reactions. In addition, it is helpful to assist the patient in developing the specific skills and behaviors required for a healthy functional life. Our group will adapt the EMDR protocol model specific for bipolar patients with a history of trauma, developed by Ahmann et al (2017), who applies EMDR in adults with Bipolar Disorder (BD) and history of trauma.	Other: Eye Movement Desensitization and Reprocessing (EMDR) Therapy; The reprocessing and desensitization of each traumatic memory occurs in eight phases. In the first two phases, the therapist identifies targets and develops a treatment plan, enhances and develops personal resources, before working on traumatic memories. In stages 3 to 6, reprocessing and desensitization of memory is done. The patient focuses on the image of the event, negative beliefs and associated bodily sensations, while moving the eyes from side to side, following the therapist's fingers or other dual attention stimuli (eg, manual touch, auditory stimulation). Phases 7 and 8 are closing and reassessing, where the therapist determines if the memory has been processed properly.; Other Names: EMDR Therapy; Other: Treatment as Usual; TAU will consist of the psychopharmacological approach appropriate to each patient according to the evaluation of a psychiatrist of childhood and adolescence's outpatient service.; Other Names: TAU
Placebo Comparator: TAU (Treatment as Usual); Patients will receive the Treatment as Usual. TAU will consist of the psychopharmacological approach appropriate to each patient according to the evaluation of a psychiatrist of childhood and adolescence's outpatient service. Patients are expected to be euthymic (or with subsyndromal symptoms) with the same medication for at least 3 months. Although the medications used by patients are relevant and taken into account in future analyzes, our group will not interfere with drug treatment. Thus, patients who require any type of drug intervention will be considered losses.	Other: Treatment as Usual; TAU will consist of the psychopharmacological approach appropriate to each patient according to the evaluation of a psychiatrist of childhood and adolescence's outpatient service.; Other Names: TAU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in the number of manic switches.	To verify if treatment with EMDR leads to a reduction in the number of manic episodes within a period of 12 months.This will be evaluated through the Young Mania Rating Scale (YMRS).	12 months
Reduction in the number of depressive episodes	To verify if treatment with EMDR leads to a reduction in the number of depressive episodes within a period of 12 months.This will be evaluated through the Children's Depression Rating Scale (CDRS).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in biological markers measured by morning salivary cortisol levels in 6 months	To analyze the biological markers related to BD, through the measurement of morning salivary cortisol levels.	6 months
Change in biological markers measured by morning salivary cortisol levels in 12 months	To analyze the biological markers related to BD, through the measurement of morning salivary cortisol levels.	12 months
Change in biological markers measured by C-reactive protein levels in 6 months.	To analyze the biological markers related to BD, through the measurement of C-reactive protein levels.	6 months
Change in biological markers measured by C-reactive protein levels in 12 months.	To analyze the biological markers related to BD, through the measurement of C-reactive protein levels.	12 months
Change in biological markers measured by Brain Derived Neurotrophic Factor levels in 6 months.	To analyze the biological markers related to BD, through the measurement of Brain Derived Neurotrophic Factor levels.	6 months
Change in biological markers measured by Brain Derived Neurotrophic Factor levels in 12 months.	To analyze the biological markers related to BD, through the measurement of Brain Derived Neurotrophic Factor levels.	12 months
Change in biological markers measured by Interleukin-1 Beta levels in 6 months.	To analyze the biological markers related to BD, through the measurement of Interleukin-1 Beta levels.	6 months
Change in biological markers measured by Interleukin-1 Beta levels in 12 months.	To analyze the biological markers related to BD, through the measurement of Interleukin-1 Beta levels.	12 months
Change in biological markers measured by Interleukin-2 levels in 6 months.	To analyze the biological markers related to BD, through the measurement of Interleukin-2 levels.	6 months
Change in biological markers measured by Interleukin-2 levels in 12 months.	To analyze the biological markers related to BD, through the measurement of Interleukin-2 levels.	12 months
Change in biological markers measured by Interleukin-4 levels in 6 months.	To analyze the biological markers related to BD, through the measurement of Interleukin-4 levels.	6 months
Change in biological markers measured by Interleukin-4 levels in 12 months.	To analyze the biological markers related to BD, through the measurement of Interleukin-4 levels.	12 months
Improvement in biological markers measured by Interleukin-6 levels in 6 months.	To analyze the biological markers related to BD, through the measurement of Interleukin-6 levels.	6 months
Change in biological markers measured by Interleukin-6 levels in 12 months.	To analyze the biological markers related to BD, through the measurement of Interleukin-6 levels.	12 months
Change in biological markers measured by Interleukin-10 levels in 6 months.	To analyze the biological markers related to BD, through the measurement of Interleukin-10 levels.	6 months
Change in biological markers measured by Interleukin-10 levels in 12 months.	To analyze the biological markers related to BD, through the measurement of Interleukin-10 levels.	12 months
Change in biological markers measured by Interferon-gamma levels in 6 months.	To analyze the biological markers related to BD, through the measurement of Interferon-gamma levels.	6 months
Change in biological markers measured by Interferon-gamma levels in 12 months.	To analyze the biological markers related to BD, through the measurement of Interferon-gamma levels.	12 months
Change in biological markers measured by Tumor Necrosis Factor alpha levels in 6 months.	To analyze the biological markers related to BD, through the measurement of Tumor Necrosis Factor alpha levels.	6 months
Change in biological markers measured by Tumor Necrosis Factor alpha levels in 12 months.	To analyze the biological markers related to BD, through the measurement of Tumor Necrosis Factor alpha levels.	12 months
Modification in neurocognitive functioning through the WASI test.	To verify if the patients treated with EMDR will present a better profile of neurocognitive functioning, evaluated by means of the Wechsler Abbreviated Intelligence Scale (WASI).	12 months
Modification in neurocognitive functioning through the WISC-III test.	To verify if the patients treated with EMDR will present a better profile of neurocognitive functioning, evaluated by means of the Wechsler Intelligence Scale for Children (WISC-III) in adolescents aged up to 17 years.	12 months
Modification in neurocognitive functioning through the WAIS-III test.	To verify if the patients treated with EMDR will present a better profile of neurocognitive functioning, evaluated by means of the Wechsler Intelligence Scale for Adults - Third Edition (WAIS-III) for adolescents over 17 years of age.	12 months
Modification in neurocognitive functioning through the MAC Battery.	To verify if patients treated with EMDR will present an improvement in processing speed, access to semantic memory, and inhibitory control evaluated by means of the Verbal Fluency Tasks of the Montreal Communication Assessment Battery (MAC Battery).	12 months
Modification in neurocognitive functioning through the Hayling Test.	To verify if patients treated with EMDR will show an improvement in the signs of inattention, impulsivity (inhibitory failure), processing speed, semantic memory, language and cognitive flexibility through the Hayling Test.	12 months
Change in neurocognitive functioning through the MAC Battery Test.	To verify if patients treated with EMDR will present an improvement in short term memory, verbal work memory and inference processing through the Oral Narrative Discourse - MAC Battery test.	12 months
Change in neurocognitive functioning through the DNE test.	To verify if patients treated with EMDR will show an improvement in Reading Comprehension through the DNE (Discurso Narrativo Escrito or Written Narrative Speech) test.	12 months
Change in neurocognitive functioning through the NEUROPSILIN test.	Check if patients treated with EMDR will show an improvement in Sentence Writing (syntax) through the Spontaneous Sentence Writing Subtest - NEUPSILIN (Instrumento de Avaliação Neuropsicológica Breve Infantil or Child Brief Neuropsychological Assessment Instrument).	12 months
Change in neurocognitive functioning through the evaluation of Comprehension of Written language.	To verify if patients treated with EMDR will present an improvement in Comprehension of written language through the Subtest Comprehension Writing - NEUPSILIN.	12 months
Change in neurocognitive functioning through the evaluation of the Visuospatial Working Memory.	To verify if patients treated with EMDR will show an improvement in the Visuospatial Working Memory through the Visuospatial Working Memory Subtest - NEUPSILIN-INF.	12 months
Change in neurocognitive functioning through the Go-no-Go Subtest.	To verify if patients treated with EMDR will show an improvement in attention and inhibitory control through the Go-no-go Subtest - NEUPSILIN-INF.	12 months
Change in neurocognitive functioning through the Words Span in Sentences Subtest.	To verify if patients treated with EMDR will present an improvement in verbal work memory through the Words Span in Sentences Subtest.	12 months
Change in neurocognitive functioning through the Five Digit Test.	To verify if patients treated with EMDR will present an improvement in the automatic and controlled processes of attention, inhibitory control, impulsivity, self-monitoring, cognitive flexibility through the Five Digit Test.	12 months
Change in neurocognitive functioning through the Psychological Attention Battery.	To verify if patients treated with EMDR will show an improvement in the attention alternated, concentrated, and divided through the Psychological Attention Battery.	12 months
Change in neurocognitive functioning through the Test of School Performance.	To verify if patients treated with EMDR will present an improvement in the school performance in writing of words in reading, writing of isolated words and arithmetic through the Test of School Performance.	12 months

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Ives C Passos, PhD, Federal University of Health Science of Porto Alegre

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2019
• Primary Completion (Anticipated): August 1, 2019
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: April 17, 2019
• First Submitted That Met QC Criteria: May 10, 2019
• First Posted (Actual): May 13, 2019

Study Record Updates

• Last Update Posted (Actual): May 13, 2019
• Last Update Submitted That Met QC Criteria: May 10, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder
• Other Study ID Numbers: 2018-0345 (Other Identifier: M D Anderson Cancer Center)

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