The association of MS with other conditions is attracting increasing attention among physicians and researchers owing to the effect of comorbidities on important considerations such as time to diagnosis, progression of disability and health-related quality of life (QoL) among patients with MS (pwMS).1 Authors of one recent cohort study in 6,932 pwMS and 68,526 matched controls reported that pwMS have an increased risk of several major comorbidities unrelated to MS, including peripheral vascular disease, depression, fracture and infection, and this was evident even before the diagnosis of MS.2 Psychiatric comorbidities are of particular interest as they are associated with a negative impact on QoL, intensification of some of the symptoms of MS (e.g. fatigue, sleep quality, disability), and reduced adherence to DMT.3,4 Some studies suggest that psychiatric comorbidities in MS are under-recognised and undertreated.1,5

Prevalence of psychiatric complications in MS

According to a recent systematic review, depressive and anxiety syndromes are the most common psychiatric comorbidities in MS, with a prevalence of around 31% and 36%, respectively, compared with 21% and 29% in the general population. However, other less common psychiatric symptoms such as obsessive–compulsive syndrome, schizophrenic syndrome and bipolar syndrome have a greater impact on QoL of pwMS than depression or anxiety.3,4

At this year’s EAN, Dr Carrasco García and colleagues presented data from a retrospective case series investigating the prevalence of less common psychiatric disorders among pwMS. Among 345 pwMS, 13 presented with a psychiatric pathology, including paranoid schizophrenia (4/13), bipolar disorder (4/13), personality disorder (3/13), neurotic disorder (1/13) and transient acute psychotic disorder (1/13).6

Despite the general tendency for an increased prevalence of psychiatric disorders in MS compared with the general population, this is not universally the case: Dr Benjaminsen and colleagues presented a study of 654 patients with MS treated in Norway, in which the prevalence of psychosis (0.6%) was lower than expected among pwMS. The reasons for this observation were not discussed, although it was noted that the validity of these results should be confirmed in other Norwegian cohorts.7

Effect of psychiatric complications in MS

Given the general increased prevalence of many psychiatric conditions among pwMS, it is important to consider the impact of the conditions on symptoms of MS. Dr Vukorepa and colleagues presented a study in 54 pwMS showing a significant association between level of depression (as measured using the Beck Depression Inventory) and level of fatigue, as measured using multiple scales. This finding has important implications for the treatment of MS, suggesting that the mutual impact of diffrent symptoms should be considered in order to improve or maintain QoL.8

A common underlying pathology?

It is not yet clear whether MS increases susceptibility to psychiatric disorders or whether they both have a common underlying pathology. This point was discussed at EAN by Dr García Carrasco, who noted that it was important to consider both potential associations because of the repercussions for treatment, functionality and prognosis of the disease.6

“It is unknown whether there is a common pathophysiological mechanism or if lesions, stress associated with chronic lesions or treatment of MS predispose to the appearance of psychiatric disorders”

– Dr García Carrasco

Psychiatric side of effects of DMTs

Although the aetiology of the increased burden of psychiatric disorders in MS is not completely understood, it has long been thought that the medications used in MS may be one contributing factor. For example, corticosteroids are known to cause a variety of neuropsychiatric side effects, while some platform therapies were initially reported to confer an increased risk of depression, although this was later disputed.9,10

A recently published systematic review concluded that none of the second-generation DMTs studied were associated with a statistically significant increased risk of any adverse psychiatric effect. Indeed, the study reported that some DMTs may in fact reduce the incidence of depressive symptoms, either directly or indirectly through a positive impact on the disease course. This is an important finding in terms of delivering optimal treatments to pwMS, as well as supporting the mental health needs of patients.9


Considerable evidence is available to show that pwMS tend to have an increased risk of psychiatric conditions. Psychiatric comorbidities can exacerbate symptoms of MS, and vice versa, and therefore the early identification and management of psychiatric syndromes is essential in order to optimise QoL in this population.


  1. Marrie RA, et al. A systematic review of the incidence and prevalence of comorbidity in multiple sclerosis: overview. Mult Scler. 2015;21:263–81.
  2. Jick S. Increased risk of comorbidities in patients before as well as after multiple sclerosis (MS) diagnosis: a study in the UK Clinical Practice Research Datalink (CPRD). In: European Committee for Treatment and Research in Multiple Sclerosis. 2018:146.
  3. Marrie RA, et al. The incidence and prevalence of psychiatric disorders in multiple sclerosis: a systematic review. Mult Scler. 2015;21:305–17.
  4. Sparaco M, et al. Psychiatric disorders in multiple sclerosis. J Neurol. 2019; published online June 13. DOI:10.1007/s00415-019-09426-6.
  5. Marrie RA, et al. The burden of mental comorbidity in multiple sclerosis: frequent, underdiagnosed, and undertreated. Mult Scler. 2009;15:385–92.
  6. Carrasco García M, et al. Psychiatric disorders in patients with multiple sclerosis: a clinical case series. In: European Academy of Neurology. 2019: POD034.
  7. Benjaminsen E, et al. Comorbidity in patients with multiple sclerosis from Nordland, Norway. In: European Academy of Neurology. 2019.
  8. Vukorepa G, et al. The impact of depression on different fatigue scales outcomes in people with multiple sclerosis. In: European Academy of Neurology. 2019: POD247.
  9. Gasim M, et al. Adverse psychiatric effects of disease-modifying therapies in multiple Sclerosis: A systematic review. Mult Scler Relat Disord. 2018;26:124–56.
  10. Chwastiak LA, et al. Psychiatric Issues in Multiple Sclerosis. Psychiatr Clin North Am. 2007;30:803–17.