Psychological interventions for enhancing adherence to disease-modifying therapies (DMT) in multiple sclerosis: a systematic review

Multiple sclerosis (MS) is the most common inflammatory neurological disease among young and middle-aged adults. Although there is no cure, disease-modifying therapies (DMT) have been shown to reduce the number and severity of exacerbations, slow disease progression and improve quality of life. However, the benefits of DMT are hampered due to poor adherence. Thus, this systematic review aims to examine the effects of psychological interventions intended to improve adherence in adults with MS. We searched CENTRAL, MEDLINE, Embase, PsycINFO and other databases and trials registers, screened reference lists to identify studies (last search July 2026). We included randomized controlled trials (RCTs) of interventions based on psychological theories and practice that aimed to improve adherence in people with MS versus usual care, no intervention, placebo treatment or another intervention. Interventions could focus on DMT initiation, re-initiation or improving ongoing adherence. We evaluated the overall certainty of evidence using the GRADE approach. We included five parallel RCTs (529 participants with MS; mean age 45.4 years; 481 female). We found some evidence that, in the short term, motivational interventions may reduce DMT discontinuation in those taking DMT and may increase reinititation of DMT in those who have stopped taking DMT. However, these findings were based on low certainty evidence so must be interpreted with caution. There was low certainty evidence that at 10-week post-treatment a motivational-interviewing CBT intervention may increase decisions to re-initiate DMT. It was unclear whether a brief MI counseling intervention improved adherence (fewer missed doses) relative to usual care. The main finding of this review is that motivational interventions may reduce, in the short term, DMT discontinuation and may increase reinititation of DMT. Evidence for the efficacy of other psychological approaches on adherence to DMT is uncertain. This conclusion is based on low-certainty evidence and should be interpreted cautiously. In addition, all five included studies were conducted in the USA and in settings that limit their generalizability. Key limitations of the review include the lack of some outcome data in included studies, and no meta-analysis due to the lack of overlap between studies in any of the outcome measures. This review highlights the dearth of studies in this area limiting scope for evidence-based recommendation for practice. There is a need for additional high-quality research to improve confidence in estimates of effect and to evaluate long-term outcomes.