Psychological Interventions for Multiple Sclerosis: Effects on Anxiety, Depression, and Cognition.
MS-PSY
Psychological Intervention in Multiple Sclerosis: Efficacy in the Treatment of Anxiety-depressive Symptoms and Cognitive Impairment.
2 other identifiers
interventional
148
1 country
1
Brief Summary
This study evaluated the efficacy of two structured psychological interventions in individuals with relapsing-remitting multiple sclerosis (RRMS). The main objective was to evaluate whether Group-Based Cognitive-Behavioral Therapy (CBT) and Psychophysiological Regulation Therapy (PRT) improved emotional well-being and objective cognitive functioning compared with Standard Care (SC). A total of 153 individuals with RRMS were assessed for eligibility, of whom 148 were randomized to one of three study conditions: Group-Based CBT, PRT, or SC (waiting-list control). Participants were allocated using a simple computer-generated randomization sequence with a 1:1:1 allocation ratio. Both active interventions were delivered in small groups over 12 weekly sessions. CBT and PRT shared a common therapeutic framework comprising psychoeducation, mindfulness, psychophysiological regulation strategies, and homework assignments. The CBT condition additionally incorporated specific cognitive-behavioral components during sessions 4-10. Assessments were conducted at baseline and immediately after completion of the 12-week intervention period using standardized psychological and neuropsychological measures. The study evaluated treatment effects across complementary domains of emotional functioning and objective cognitive performance.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Feb 2015
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2019
CompletedFirst Submitted
Initial submission to the registry
November 19, 2025
CompletedFirst Posted
Study publicly available on registry
December 9, 2025
CompletedSeptember 30, 2026
September 1, 2026
3.9 years
November 19, 2025
September 25, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (12)
Fatigue Severity Scale (FSS) - Total Score
Description: Change in fatigue severity measured with the Fatigue Severity Scale (FSS; Krupp et al., 1989). Scale range: 9-63 points (9 items scored 1-7). Interpretation: Higher scores indicate greater fatigue severity.
Baseline and 12 weeks.
Multiple Sclerosis Quality of Life-54 (MSQoL-54) - Total and Subscale Scores
Description: Change in quality of life measured with the Multiple Sclerosis Quality of Life-54 (MSQoL-54; Vickrey, Hays, Harooni, Myers \& Ellison, 1995), including physical and mental health composite scores and individual subscales. Scale range: 0-100 points. Interpretation: Higher scores indicate better quality of life.
Baseline and 12 weeks.
Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) - Total Score
Description: Change in perceived cognitive functioning measured with the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ; Benedict et al., 2003). Scale range: 0-60 points. Interpretation: Higher scores indicate greater perceived cognitive impairment.
Baseline and 12 weeks.
Verbal Selective Reminding Test (SRT) - Total Recall Score
Change in verbal learning and memory performance measured with the Verbal Selective Reminding Test (SRT), part of the BRB-N (Rao, 1990). (Scale range 0-72). Interpretation: Higher scores indicate better performance.
Baseline and 12 weeks.
10/36 Spatial Recall Test (SPART) - Total Recall Score
Description: Change in visuospatial learning and memory measured with the 10/36 Spatial Recall Test (SPART), part of the BRB-N (Rao, 1990). Scale range: 0-36. Interpretation: Higher scores indicate better performance.
Baseline and 12 weeks.
Paced Auditory Serial Addition Test (PASAT) - 3-Second Version
Description: Change in complex attention and working memory measured with the PASAT (3-second version), part of the BRB-N (Rao, 1990). Scale range: 0-60 correct responses. Interpretation: Higher scores indicate better performance.
Baseline and 12 weeks.
Symbol Digit Modalities Test (SDMT) - Oral Version
Description: Change in attention and processing speed measured with the Symbol Digit Modalities Test (SDMT), part of the BRB-N (Rao, 1990). Scale range: 0-110 correct responses. Interpretation: Higher scores indicate better performance.
Baseline and 12 weeks.
Controlled Oral Word Association Test (COWAT) - Semantic Fluency ("Animals" Category)
Description: Change in semantic verbal fluency measured with the Controlled Oral Word Association Test (COWAT), Semantic Fluency subtest (animals category). Scale range: Number of correct animals named in 60 seconds (typically 0-40). Interpretation: Higher scores indicate better performance.
Baseline and 12 weeks.
Controlled Oral Word Association Test (COWAT) - Phonemic Fluency (F-A-S Letters)
Description: Change in phonemic verbal fluency measured with the Controlled Oral Word Association Test (COWAT), Phonemic Fluency subtest (letters F, A, and S). Scale range: Total number of correct words generated across the three letters in 60 seconds each (typically 0-60). Interpretation: Higher scores indicate better performance.
Baseline and 12 weeks.
Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A)
Description: Change in anxiety symptoms measured with the Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A; Zigmond \& Snaith, 1983). Scale range: 0-21 points. Interpretation: Higher scores indicate greater anxiety severity.
Baseline and 12 weeks.
Beck Depression Inventory-II (BDI-II) - Total Score
Description: Change in depressive symptoms measured with the Beck Depression Inventory-II (BDI-II; Beck et al., 1996). Scale range: 0-63 points. Interpretation: Higher scores indicate greater depressive severity.
Baseline and 12 weeks.
Inventario de Situaciones y Respuestas de Ansiedad (ISRA) - Total Score
Description: Change in cognitive, physiological, and motor anxiety responses measured with the Inventario de Situaciones y Respuestas de Ansiedad (ISRA; Miguel-Tobal \& Cano-Vindel, 1994). Scale range: 0-100+ (higher scores = greater anxiety response). Interpretation: Higher scores indicate greater anxiety reactivity.
Baseline and 12 weeks.
Secondary Outcomes (8)
Recent Life Changes Questionnaire (RLCQ) - Total Score
Baseline and 12 weeks.
Symptom Checklist-90-Revised (SCL-90-R) - Global Severity Index (GSI)
Baseline and 12 weeks.
Cognitive Triad Inventory (CTI) - Total Score
Baseline and 12 weeks.
Intolerance of Uncertainty Scale (IUS) - Total Score
Baseline and 12 weeks.
Social Support Questionnaire (SSQ-6) - Total Score
Baseline and 12 weeks.
- +3 more secondary outcomes
Other Outcomes (1)
Disease-Modifying and Symptomatic Treatment Status
Baseline and 12 weeks.
Study Arms (3)
Cognitive Behavioral Therapy (CBT)
EXPERIMENTALParticipants receive a structured 12-week cognitive-behavioral group intervention designed to improve stress coping and reduce anxiety-depressive symptoms. The program includes psychoeducation, mindfulness, behavioral activation, cognitive restructuring, self-instruction training, and social skills development. Intervention: Behavioral: Cognitive Behavioral Therapy
Psychophysiological Regulation Therapy (PRT)
EXPERIMENTALParticipants receive a structured 12-week group intervention emphasizing psychophysiological self-regulation. The program includes psychoeducation, mindfulness, relaxation, breathing control, and biofeedback-based exercises aimed at reducing emotional distress and enhancing self-regulation.
Standard Care (SC)
NO INTERVENTIONParticipants in the control group remain on a waiting list and receive standard medical care provided by the Multiple Sclerosis Unit during the study period. After study completion, they are offered participation in one of the active interventions.
Interventions
A structured 12-week group-based intervention emphasizing psychophysiological self-regulation through psychoeducation, mindfulness, relaxation, breathing control, and biofeedback-based exercises to reduce emotional distress and promote physiological balance.
A structured 12-week group-based cognitive-behavioral intervention including psychoeducation, mindfulness training, behavioral activation, cognitive restructuring, self-instruction training, and social skills development. Designed to improve coping, reduce anxiety-depressive symptoms, and enhance cognitive and emotional functioning.
Eligibility Criteria
You may qualify if:
- Diagnosis of relapsing-remitting multiple sclerosis according to standard clinical criteria.
- Expanded Disability Status Scale (EDSS) score between 0 and 3.5.
- Mild to moderate cognitive impairment defined as: up to two BRB-N subtests with scores \< -2 SD.
- Presence of anxiety or depressive symptoms defined as:
- HADS: score \> 8 on one or both subscales, and/or
- BDI-II: score \> 8.
- Stable disease-modifying treatment for ≥ 3 months.
- Ability to provide written informed consent.
You may not qualify if:
- Progressive forms of multiple sclerosis (SPMS or PPMS).
- Severe cognitive impairment preventing participation in psychological sessions.
- Active psychiatric or neurological disorders unrelated to MS.
- Participation in another psychological or pharmacological intervention study.
- Recent initiation or modification of disease-modifying treatment (\< 3 months).
- Substance abuse or dependence within the past year.
- Inability to provide informed consent.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Moisés Bermúdez Hernándezlead
- University of La Lagunacollaborator
Study Sites (1)
Faculty of Psychology, University of La Laguna Department of Clinical Psychology, Psychobiology and Methodology of Behavioral Sciences Campus de Guajara, Calle Heraclio Sánchez, s/n 38200 San Cristóbal de La Laguna, Santa Cruz de Tenerife Spain
San Cristóbal de La Laguna, Santa Cruz de Tenerife, 38200, Spain
Related Publications (6)
Scandiffio J, Langer LK, Senthilnathan V, Feng G, Sureshkumar A, Bromberg M, Babineau J, Donkers SJ, Knox KB, Bruno T, Walker LAS, Bayley MT, Simpson R. Effects of psychological therapies in people with multiple sclerosis: a systematic review and network meta-analysis of randomized controlled trials. J Neurol. 2025 Aug 20;272(9):584. doi: 10.1007/s00415-025-13315-6.
PMID: 40833620BACKGROUNDLucien A, Francis H, Wu W, Woldhuis T, Gandy M. The efficacy of cognitive behavioural therapy for depression and anxiety in multiple sclerosis: A systematic review and meta-analysis. Mult Scler Relat Disord. 2024 Nov;91:105858. doi: 10.1016/j.msard.2024.105858. Epub 2024 Sep 3.
PMID: 39276596BACKGROUNDMoss-Morris R, McCrone P, Yardley L, van Kessel K, Wills G, Dennison L. A pilot randomised controlled trial of an Internet-based cognitive behavioural therapy self-management programme (MS Invigor8) for multiple sclerosis fatigue. Behav Res Ther. 2012 Jun;50(6):415-21. doi: 10.1016/j.brat.2012.03.001. Epub 2012 Mar 13.
PMID: 22516321BACKGROUNDDe Meo E, Portaccio E, Bonacchi R, Giovannoli J, Niccolai C, Amato MP. An update on the treatment and management of cognitive dysfunction in patients with multiple sclerosis. Expert Rev Neurother. 2025 Feb;25(2):227-243. doi: 10.1080/14737175.2025.2450788. Epub 2025 Jan 16.
PMID: 39801437BACKGROUNDCuijpers P, Karyotaki E, Weitz E, Andersson G, Hollon SD, van Straten A. The effects of psychotherapies for major depression in adults on remission, recovery and improvement: a meta-analysis. J Affect Disord. 2014 Apr;159:118-26. doi: 10.1016/j.jad.2014.02.026. Epub 2014 Feb 24.
PMID: 24679399BACKGROUNDAmato MP, Langdon D, Montalban X, Benedict RH, DeLuca J, Krupp LB, Thompson AJ, Comi G. Treatment of cognitive impairment in multiple sclerosis: position paper. J Neurol. 2013 Jun;260(6):1452-68. doi: 10.1007/s00415-012-6678-0. Epub 2012 Nov 23.
PMID: 23180174BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- Outcome assessors were blinded to participants' group allocation. Participants and therapists were aware of the assigned intervention, but evaluators conducting clinical and neuropsychological assessments did not have access to treatment information to minimize bias in data collection.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator and Researcher, Hospital Universitario Nuestra Señora de Candelaria (HUNSC); Professor of Psychology, University of La Laguna
Study Record Dates
First Submitted
November 19, 2025
First Posted
December 9, 2025
Study Start
February 1, 2015
Primary Completion
January 1, 2019
Study Completion
January 1, 2019
Last Updated
September 30, 2026
Record last verified: 2026-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- IPD and supporting documents will be available beginning 12 months after publication of the main results and will remain accessible for 5 years thereafter.
- Access Criteria
- Qualified researchers affiliated with academic or non-profit institutions may request access to de-identified individual participant data (IPD) and supporting documents (protocol, SAP, ICF, CSR) for scientific and non-commercial purposes. Requests must be submitted to the corresponding author, Dr. Moisés Bermúdez Hernández (mbermudh@ull.edu.es). Access will be granted following review and approval by the study's ethics committee and in compliance with GDPR and institutional data-sharing policies.
De-identified individual participant data (IPD) will be made available upon reasonable request to the corresponding author, Dr. Moisés Bermúdez Hernández (mbermudh@ull.edu.es), for academic and non-commercial research purposes. Data will be fully anonymized in compliance with institutional and ethical regulations and the European General Data Protection Regulation (GDPR).