Review ArticlePrevalence of depression and anxiety in Multiple Sclerosis: A systematic review and meta-analysis
Introduction
Depression and anxiety are common in Multiple Sclerosis (MS) and elevated compared with the general population [1]. Explanations for comorbidity are multifactorial and concern a complex interplay of variables. Depression and anxiety could be natural reactions to the unpredictable course of a disabling and chronic disease. Further, MS patients could be predisposed for depression or anxiety by several psychosocial risk factors such as inadequate coping or insufficient social support, or by MS-related biological processes such as changes in brain structure or in immunological and inflammatory pathways [2], [3], [4], [5]. In reverse, depression and anxiety may adversely affect health status by increasing symptom burden, negatively influencing adherence to treatment regimens or by direct pathophysiological effects on immunity [6], [7]. Depression and anxiety in MS patients are related to lower quality of life, cognitive dysfunction, elevated suicide risk, and working problems [4], [8]. Since depression and anxiety in MS seem to worsen over time and as they are often treatable, early recognition is important and knowledge on their presence and management should be further improved in order to enhance clinical care [4], [9], [10], [11].
The increased risk of depression or anxiety in MS has often been reported but prevalence rates vary widely from 14% up to 54% [9], [12]. This variation could be due to a number of methodological issues, such as differences in definitions, instruments and diagnostic criteria used, and size and nature of the population studied [13]. Often the terms ‘depression’ and ‘anxiety’ refer to clinically significant symptoms revealed by self-report scales of different quality, which makes it difficult to compare findings [9], [14]. Besides, these scales cannot be used to establish a formal diagnosis of psychiatric disorders and tend to overestimate prevalence rates as compared with diagnostic interviews [13], [15]. Further, depressive and anxiety symptomatology in MS has frequently been studied in small MS samples attending MS-clinics or in inpatient settings, underrepresenting patients who are coping well in the community [1], [16], [17].
A systematic review pooling data from population-based studies showed that depression and anxiety both affect > 20% of the MS population [14]. Although the authors performed sensitivity analyses and focused on high quality studies, a high degree of heterogeneity was observed. This implied that prevalence rates varied considerably between the included studies, hampering solid conclusions for the MS population. It is therefore clearly of interest to determine the causes of this heterogeneity as is also suggested by the Cochrane Handbook [18]. This has, to the best of our knowledge, not been previously performed. In addition to revealing the sources of heterogeneity and improving prevalence estimates, it might also offer explanations for the elevated prevalence rates in MS.
In this systematic review and meta-analysis, we therefore aimed to provide a targeted analysis of studies on the prevalence of depression and anxiety in MS and 1) estimate the prevalence of depression and anxiety in MS, and in addition 2) explore sources of heterogeneity by performing subgroup analyses. We evaluated whether the average prevalence estimates varied in relation to a) different definitions of depression and anxiety (disorder vs clinically significant symptoms); b) various methods of assessment and prevalence period; c) quality of research papers; d) patient recruitment resources; and e) different regions. By exploring the heterogeneity by conducting subgroup analyses, we strived to obtain a more comprehensive view on the prevalence of depression and anxiety in MS and its implications for future research.
Section snippets
Search strategy
A systematic computerized search in PubMed, EMBASE, and Psycinfo was completed in December 2014 for studies on depression and anxiety in Multiple Sclerosis. In collaboration with the librarian, a search strategy was developed which was adjusted correspondingly for each of the databases: The medical subject headings (MeSH) terms ‘Depression’, ‘Depressive Disorder’, ‘Depressive’, ‘Anxiety’, ‘Anxiety Disorders’, ‘Anxious’, ‘Emotions’, ‘Affective Symptoms’, ‘Mood Disorders’, ‘Distress’,
Results
The literature search identified 2999 articles published between August 1965 and December 2014. Examination of titles and abstracts resulted in 112 publications that were considered for inclusion. After full-text assessment, 58 articles met the inclusion criteria and were included in this review with a total sample size of 87,756 MS patients [11], [17], [28], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61],
Discussion
Aim of this systematic review and meta-analysis was to estimate the prevalence of depression and anxiety in MS, and specifically to explore sources of heterogeneity by extensive analyses. This review elaborated on previous reviews on depression and anxiety in MS [1], [12], [14]. It included a large sample with > 87.000 MS patients and investigated 23 studies that were not considered previously [14]. We demonstrated consistent evidence of high prevalence rates of depression (31%) and anxiety
Conflicts of interest and source of funding
There are no conflicts of interests for all authors. This work was supported by the Stichting MS Research (Grant number 09-678).
Acknowledgements
We would like to express our thanks and acknowledge the help of Caroline Planting in the development of our search strategy.
References (120)
- et al.
Depression and immunity: inflammation and depressive symptoms in multiple sclerosis
Neurol. Clin.
(2006) - et al.
The association of depression and anxiety with medical symptom burden in patients with chronic medical illness
Gen. Hosp. Psychiatry
(2007) - et al.
Depression in persons with multiple sclerosis
Phys. Med. Rehabil. Clin. N. Am.
(2005) - et al.
BetaPlus study group, supportive strategies to improve adherence to IFN β-1b in multiple sclerosis–results of the βPlus observational cohort study
J. Neurol. Sci.
(2011) - et al.
Suicidal ideation in multiple sclerosis
Arch. Phys. Med. Rehabil.
(2006) - et al.
Fatigue and psychiatric illness in a large community sample of persons with multiple sclerosis
J. Psychosom. Res.
(2005) - et al.
Multiple sclerosis and bipolar disorders: the burden of comorbidity and its consequences on quality of life
J. Affect. Disord.
(2014) - et al.
Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement
J. Clin. Epidemiol.
(2012) - et al.
Validation study of prevalence and correlates of depressive symptomatology in multiple sclerosis
Gen. Hosp. Psychiatry
(2008) - et al.
Depression in multiple sclerosis: a longitudinal analysis
Arch. Psychiatr. Nurs.
(2007)