A tailored cognitive behavioural therapy intervention for depression in those newly diagnosed with multiple sclerosis...

Multiple sclerosis (MS) is an unpredictable, chronic neurological disease accompanied with high rates of depression and anxiety, particularly in the early stages of the MS diagnosis. There is evidence to suggest that cognitive behavioural therapy (CBT) is effective for the treatment of depressive symptoms in individuals with MS; however, there are limited tailored CBT interventions designed to be offered in the newly diagnosed period that target mild to moderate depressive symptoms. The aim of this trial is to assess the efficacy of a tailored CBT intervention compared to a supportive listening (SL) intervention amongst individuals who are newly diagnosed with MS with mild to moderate depressive symptoms.

ACTION-MS, was a prospective, randomised, controlled, assessor-blinded, stratified, active comparator efficacy trial. Eligible participants were aged 18 years or older with a neurologist confirmed diagnosis of relapse remitting MS and confirmed MS disease duration of 5 years or less (median duration 16 months (IQR 5-36 months)), with mild to moderate depressive symptoms based on a score of 14 to 28 on the Beck Depression Inventory II (BDI-II) and attending one of four MS centres in metropolitan Melbourne, Australia. Patients were randomly assigned (1:1) to receive the CBT or the SL intervention for 8 weeks (end of intervention) which were delivered by a clinical or provisional psychologists in weekly 60-min sessions. Participants attended assessments with clinical or provisional psychologists who were blinded to intervention allocation and where they completed a diagnostic interview, the BICAMS and online questionnaires at baseline, week 8 (end of intervention) and week 28. The primary outcome was proportion of participants who had a clinically meaningful 10 point or more reduction in depression severity using the BDI-II at week 8 (end of the intervention) compared to baseline. Data was analysed on an intention-to-treat basis. The trial was registered with the International Standard Randomised Controlled Trial Number (ISRCTN) registry (number ISRCTN63987586) and is complete.

Between 20/10/2017 and 1/11/2023, we randomly assigned 60 participants to the ACTION-MS group (n = 30) or the SL group (n = 30). All participants completed their allocated intervention. The median age of participants was 36 years (IQR 28-45), the majority were diagnosed with relapse remitting MS (56/60; 93·3%) for 16 months (IQR 5-36), most identified as female (48/60; 80%) and as Anglo-Celtic Australian (42/60; 70%). The primary outcome was different between the two groups: 19 (63.3%) participants in the CBT group and 10 (33·3%) in the SL group had a clinically meaningful 10-point reduction on the BDI-II at week 8 (end of intervention) compared to baseline depressive symptoms as measured with the BDI-II (adjusted odds ratio [aOR 3·62 [95% CI 1·23 to 10.67], p = 0·01). Participants in the CBT group reported lower scores on the BDI-II scale at week 8 (adjusted mean difference - 9.19 [95% CI -14.67 to -3.72], p = 0·001) and week 28 (adjusted mean difference - 12·47 [95% CI -17·06 to -7.86], p < 0·001) compared to patients in the SL group. There were more participants in the CBT group who did not meet DSM-IV criteria for major depressive disorder and major depressive episode than in the SL group at week 8 (end of intervention) and for major depressive disorder at week 28. Participants in the tailored CBT group also reported significant reductions in anxiety, pain impact and MS illness acceptance at week 8 (end of the intervention) and these reductions were maintained at week 28 compared to participants in the SL group. Those in the CBT group reported greater improvements in sleep quality, quality of life, MS illness acceptance at week 8 (end of intervention) and week 28. Those in the CBT group also reported improvements in problem solving coping and lower levels of perceived deficits at week 8 (end of the intervention) and improvements in resilience, MS related physical and mental quality of life at week 28. Participants in the tailored CBT group also showed cognitive improvements in processing speed and sustained attention (SDMT) and visuospatial memory (BVMT-R) at week 8 (end of the intervention) with changes on the BVMT-R being sustained in week 28 compared to those in the SL group. No serious events were reported.

Our findings suggest that mild to moderate depressive symptoms in those newly diagnosed with MS can be effectively treated with the tailored CBT based intervention.

This study was funded by a MS Australia project grant (Grant Number: 15-013) and a Melbourne School of Psychological Sciences Research Incentives Grant. Research in context EVIDENCE BEFORE THIS STUDY: We searched MEDLINE, PUBMED and EMBASE OVID (from database inception) on 10 March 2025 using search terms 'multiple sclerosis', 'depression' and 'cognitive behavioural therapy'. Findings revealed support for the use of a tailored cognitive behavioural therapy (CBT) for the treatment of depressive symptoms in individuals with relapse remitting multiple sclerosis. No studies were found that examined whether tailored CBT, compared to a SL intervention, was effective in the treatment of mild to moderate depressive symptoms in individuals within 2 years of being diagnosed with relapse remitting multiple sclerosis.

To our knowledge, this is the first clinical trial that met its clinical endpoint with an intention-to-treat analysis and show the effects of a tailored CBT intervention on mild to moderate depressive symptoms in those newly diagnosed with MS. In the ACTION-MS trial, clinically meaningful reductions in depressive symptoms were seen in individuals newly diagnosed with MS and treatment effects extended to week 28. Compared to the SL group, 60% (18/30) of participants in the CBT group did not meet criteria for major depressive disorder and none met criteria for major depressive episode at week 8 (end of the intervention) and week 28. The tailored CBT intervention also showed additional mental health and cognitive benefits with patients in the CBT group reporting reductions in level of anxiety and pain impact and improvements in sleep quality, quality of life, MS illness acceptance and visuospatial memory at week 8 (end of the intervention) with these being sustained at week 28. The ACTION-MS trial overcomes many of the methodological limitations in the few studies available in this area including enrolling individuals within 2 years of an MS diagnosis, using an active comparator intervention, and adequate statistical power with the potential to demonstrate the applicability of our conclusions using a 28 week follow up.

The current study suggests that, compared to a SL intervention, tailored CBT is efficacious in reducing depressive symptoms in participants newly diagnosed with MS who with mild to moderate depressive symptoms. Treatment of mild to moderate depressive symptoms with tailored CBT was also associated with reductions in levels of anxiety and pain impact and improvements in sleep quality, quality of life, problem solving coping, MS illness acceptance and improvements in processing speed, attention and visuospatial memory in individuals with MS. The current tailored CBT intervention increases depression treatment options for individuals newly diagnosed with relapse remitting MS with mild to moderate depressive symptoms.