Internet-Delivered Cognitive Behavioral Therapy Improves Neurovegetative Symptoms and Positive Affect in Persons with Multiple Sclerosis: Preliminary Results from a Randomized, Controlled Phase III Clinical Trial

Megan Bradson, The Pennsylvania State University, University Park, United States
Garrett Thomas, The Pennsylvania State University, University Park, United States
McKenna Sakamoto, The Pennsylvania State University, University Park, United States
Stefan Gold, Institute of Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Center Hamburg-Eppendorf; Department of Psychiatry and Psychotherapy, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin; Division of Psychosomatic Medicine, Medical Department, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Hamburg; Berlin; Berlin, Germany
Peter Arnett, The Pennsylvania State University, University Park, United States


The lifetime prevalence of depression is estimated to be approximately 50% in multiple sclerosis (MS). A randomized, controlled phase III clinical trial was recently conducted to examine the efficacy and safety of an MS-specific, internet-delivered cognitive behavioral therapy (iCBT) program for the treatment of depression in an MS sample (Gold et al., in press). Researchers found that both the stand-alone and therapist-guided versions of the iCBT intervention significantly reduced depressive symptoms (BDI-II) in persons with MS (PwMS) compared to the waitlist control condition; there was no significant difference in post-intervention depressive symptoms between the stand-alone iCBT and guided iCBT conditions. To better understand the possible mechanism of action, the current study aims to explore whether iCBT differentially affects the unique features of depressive symptomatology: dysphoric mood, negative cognitive biases, neurovegetative or somatic symptoms, and positive affect. We predicted that the negatively valenced depression symptoms (i.e., mood, evaluative, and neurovegetative symptoms) would significantly decrease, while positive affect would significantly increase, as a function of the iCBT intervention.

Participants and Methods:

27 PwMS received one of two versions of iCBT [stand-alone (n = 15) or therapist-guided (n =12)]. All participants completed a comprehensive neuropsychological battery and psychosocial questionnaires pre- and post-intervention. The Chicago Multiscale Depression Inventory (CMDI) was used to measure the unique features of depression, including dysphoric mood, negative cognitive biases, and neurovegetative symptoms, as well as positive affect. As such, the Mood, Evaluative, Neurovegetative, and Positive Affect scales were derived from the CMDI. Paired samples -tests were conducted to determine the effect of the iCBT intervention on each CMDI scale.


A paired samples t-test revealed that neurovegetative symptoms significantly decreased post-iCBT (M = 40.81, SD = 10.11) compared to baseline (M = 43.00, SD = 8.97), t(26) = 2.41 p = .023, d = .47. Results also indicated that, compared to baseline (M = 22.30, SD = 3.80), positive affect significantly increased following iCBT (M = 24.70, SD = 5.57), t(26) = -2.42, p = .023, d = -.47. Mood and evaluative symptoms also decreased following iCBT, though the effect of iCBT on these symptoms was not statistically significant (p > .05).


The iCBT intervention significantly reduced self-reported neurovegetative symptoms and increased positive affect in our sample of PwMS. However, iCBT did not significantly reduce dysphoric mood symptoms or negatively biased thought processes (i.e., evaluative symptoms). Therefore, these findings suggest that iCBT may be more effective in improving certain features of depression (i.e., reducing somatic symptoms, increasing positive affect) than others (i.e., mood and evaluative symptoms) among PwMS. Further, preliminary results suggest that the efficacy of iCBT for treating depression symptoms in PwMS may be driven by a decrease in neurovegetative symptoms and an increase in positive affect. This study highlights the importance of identifying which features of depressive symptoms are most salient to an individual with MS in order to accurately recommend the most effective treatment.

Category: Multiple Sclerosis/ALS/Demyelinating Disorders

Keyword 1: depression
Keyword 2: clinical trials
Keyword 3: multiple sclerosis