Article Text

Original research
Quality of life in adults with multiple sclerosis: a systematic review
  1. Irene Gil-González1,
  2. Agustín Martín-Rodríguez1,
  3. Rupert Conrad2,
  4. María Ángeles Pérez-San-Gregorio1
  1. 1Personality, Assessment, and Psychological Treatment, University of Seville, Seville, Spain
  2. 2Department of Psychosomatic Medicine and Psychotherapy, University Hospital Bonn, Bonn, Germany
  1. Correspondence to Irene Gil-González; igil2{at}


Objective In recent years, quality of life (QoL) in multiple sclerosis (MS) has been gaining considerable importance in clinical research and practice. Against this backdrop, this systematic review aimed to provide a broad overview of clinical, sociodemographic and psychosocial risk and protective factors for QoL in adults with MS and analyse psychological interventions for improving QoL.

Method The literature search was conducted in the Scopus, Web of Science and ProQuest electronic databases. Document type was limited to articles written in English, published from January 1, 2014, to January 31, 2019. Information from the selected articles was extracted using a coding sheet and then qualitatively synthesised.

Results The search identified 4886 records. After duplicate removal and screening, 106 articles met the inclusion and exclusion criteria for qualitative synthesis and were assessed for study quality. Disability, fatigue, depression, cognitive impairment and unemployment were consistently identified as QoL risk factors, whereas higher self-esteem, self-efficacy, resilience and social support proved to be protective. The review analysed a wide spectrum of approaches for QoL psychological intervention, such as mindfulness, cognitive behavioural therapy, self-help groups and self-management. The majority of interventions were successful in improving various aspects of QoL.

Conclusion Adequate biopsychosocial assessment is of vital importance to treat risk and promote protective factors to improve QoL in patients with MS in general care practice.

  • multiple sclerosis
  • mental health
  • adult neurology

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Strengths and limitations of this study

  • This is the first systematic review of risk factors and psychological intervention for quality of life in multiple sclerosis for over a decade.

  • A comprehensive and robust search strategy and strict inclusion criteria were employed to cover all the relevant evidence.

  • Careful standardised risk of bias was assessed in all 106 studies included.

  • Due to heterogeneity of the studies, only qualitative synthesis of results was possible.

  • The huge number of publications made it necessary to limit the time span to the 5-year period from January 1, 2014, to January 31, 2019.


The Constitution of the WHO declares health to be ‘…a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity’.1 Quality of life (QoL) is a multidimensional concept that encompasses the domains included in this definition of health.2 3 Its introduction in medical literature dates back to 1960,4 with its importance continuously growing to date.5

Multiple sclerosis (MS) is a chronic neurodegenerative condition characterised by a wide range of symptoms and a highly unpredictable prognosis, which can severely affect patient QoL.6–8 Patients with MS tend to report lower QoL than the general population.9–12 This diminished QoL may be due to their impaired functioning in daily living, more so if the help of caregivers is required, impeding family relations, work and social dynamics.13 14 The impact of MS on QoL can be affected by numerous disease-related factors, such as disability level or MS type, and individual factors such as social support, education, age or employment.15–18

Identification of risk and protective factors is a key point in implementing strategies to improve patient’s QoL.7 In this context, all influences must be considered to contribute to QoL in MS.7 19 In addition to providing practitioners with useful information on the impact of symptoms and therapy on the patient’s life, QoL is also an indicator of treatment success and a predictor of disease progression.20–22

In view of its relevance in healthcare research, the need to compile and condense available scientific evidence on the subject is urgent. Against this backdrop, this systematic review gives a comprehensive overview of risk and protective factors related to QoL in MS as well as relevant psychological interventions. The growing number of studies on this subject2 22 provides a vast amount of data, which due to the inconsistency of findings needs careful assessment to come to evidence-based conclusions.


This systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.23 As a review of prior publications, ethical approval (or informed consent) was unnecessary. A review protocol is available from the corresponding author on request.

Search strategy

The systematic search focused on journal articles published between January 1, 2014, and January 31, 2019. The Scopus, Web of Science and ProQuest databases were searched in February and March 2019. The key words used were (‘multiple sclerosis’) AND (‘quality of life’ OR ‘health-related quality of life’ OR ‘well-being’ OR ‘well-being’ OR ‘life satisfaction’). The search terms were intentionally broad to ensure wide coverage of the literature. The search field was limited to ‘title/abstract’ and language was limited to ‘English’. The complete research string is reported under online supplemental file 1.

There is no published systematic review on this topic in the Cochrane Library.

Study selection

First, title and abstract were screened to identify suitable articles for full text review. The screening process was performed independently by two researchers. Any disagreement about study selection was resolved by consensus with a third reviewer.

Inclusion criteria were the following:

  1. Studies primarily focusing on QoL determinants and psychological intervention to improve it.

  2. Study participants aged over 18 years with a confirmed MS diagnosis.

The following exclusion criteria were applied:

  1. Non-psychological intervention.

  2. Not primary research studies (systematic reviews, meta-analyses, protocols and clinical guidelines were excluded).

  3. Studies on the development and validation of QoL measurement instruments.

  4. QoL risk or intervention studies for healthy behaviour, cognitive rehabilitation, physical activity or pharmacological treatment.

  5. Studies on comorbidity with another illness or mental health diagnosis.

  6. Sample selection based on a special condition (eg, only employees or patients with MS under certain pharmacological treatment).

  7. Studies not using a validated QoL measurement tool.

Quality assessment

The methodological quality of the studies was appraised with a well-established standardised 12-item checklist,24 in which every item represents a methodological feature: inclusion/exclusion criteria, methodology/design, attrition rate, attrition between-groups, exclusions after, follow-up, occasion of measurements, pre/post measures, dependent variables, control techniques, construct definition and imputing missing data. The codification criteria proposed by the checklist authors was used. No article was excluded from quality appraisal.

Data abstraction

Data were extracted from selected articles based on a previously designed coding sheet. The pilot study was approved by consensus. The information extracted included: title, authors and publication year, country (city), design, sample characteristics, study variables and measurement tools, main results and conclusions. After extraction, the information was independently reviewed by two authors to avoid errors or omitting data.

A meta-analysis was not possible due to the heterogeneity of study designs and outcomes, so a narrative synthesis was undertaken.


Literature screening

A total of 4886 articles were initially identified from Scopus, Web of Science and ProQuest. After removal of duplicates and abstract analysis, 188 studies were eligible for full text review. Finally, 106 were selected for the narrative analysis. The selection process is detailed below in a PRISMA flow diagram (figure 1).

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of selection process. MS, multiple sclerosis; QoL, quality of life.

Methodological quality

Methodological quality scores using the 12-item checklist are summarised in table 1.

Table 1

Methodological quality of articles (n=106)

Study characteristics

The articles included were analysed by their primary and secondary outcomes. Seventy studies analysed QoL risk and protective factors (table 2), 11 focused on the development of QoL at different ages and times in the disease (table 3) and 25 studied the effect of psychological intervention on QoL in MS (table 4).

Table 2

Characteristics of included articles

Table 3

Characteristics of included studies

Table 4

Characteristics of the included articles

All the articles included employed standardised and validated QoL measurement instruments; 64 studies evaluated QoL with a generic measure and 50 studies made use of a disease-specific measure. The Short Form Health Survey 36 (SF-36) was mainly used (n=29) as a generic measure and Multiple Sclerosis Quality of Life-54 (MSQoL-54) (n=28) as a disease-specific measure. Finally, 11 studies used more than one measure to evaluate QoL. The study designs were mostly cross-sectional (n=74), and sample sizes ranged from 7 to 74 451 participants.

The main findings of the articles are summarised below.

Risk and protective MS QoL factors

Factors influencing MS patient’s QoL are summarised in table 2.

Clinical factors

Functional impairment as assessed by the Expanded Disability Status Scale (EDSS) level was one of the leading causes of diminished QoL.25–35 Disease duration,30 31 progressive type,26 36 37 progressive MS onset38 and relapses in the last 3 months were further relevant factors negatively affecting QoL.26

Several studies found a significant association between the severity and number of symptoms and the decline of QoL in MS.33 37–41 Fatigue was identified as a main risk factor.28 29 39 40 42–52

A number of articles stated the importance of sensory53 54 and motor49 52 54 55 dysfunction on QoL, including paralysis, walking difficulties, balance, stiffness and spasms as motor problems, specifically emphasising pain34 39 50 51 55 56 and spasticity,49 57 58 and low sensory sensitivity and sensation avoidance as sensory problems.

Bladder dysfunction,34 59 60 bowel dysfunction,34 sexual,60–62 and sleeping34 39 48 63 64 problems contributed to deterioration of QoL.

A diversity of cognitive impairments, for instance, cognitive fatigue, memory loss and planning/organisational dysfunction, were recognised as risk factors by a number of studies.39 50 52 53 65–67 Sgaramella et al68 showed that maintaining executive functioning was a protective factor of QoL. This was also the only study on the important subject of cognitive reserve and QoL.

Psychosocial factors

Emotional symptoms

Some studies reported the beneficial effect of emotional stability on QoL69 and the harmful effect of emotional problems.52 70 The emotional symptom studied most was depression28 29 32 34 35 39 40 51 55 65 69 71–75 followed by anxiety.39 40 51 69 71–74 76 Both symptoms were confirmed as risk factors for QoL in MS. Similarly, high levels of perceived stress,37 40 41 anger expression-in74 and apathy29 were identified as factors related to emotional regulation negatively affecting QoL in MS.

Personality domains

The role of personality domains was explored in several studies. Cyclothymic and depressive temperament were associated with a lower QoL in MS, in contrast to hyperthymic temperament, which was associated with higher QoL.77 Another study recognised extraversion as a personality trait related to higher QoL levels.69 Cioncoloni et al34 recognised introverted personality as a risk factor for QoL in MS, and finally, type D personality was another relevant factor.78

Coping strategies

Results with regard to coping strategies were consistent. Active coping, problem resolution, planning problem solving, cognitive positive restructuring, emotional and instrumental social support, emotional expression, acceptance and growth were related to a higher QoL in MS.51 71 79–82 In addition, Grech et al80 found a similar connection with restrained coping, Strober51 with humour and Mikula et al82 with stopping unpleasant emotion coping strategies. On the contrary, problem avoidance,71 81 behavioural disengagement,51 80 distancing,81 self-distraction,79 denial,51 79 emotion-focused and venting coping strategies,80 social withdrawal,71 wishful thinking,71 self-criticism,71 81 suppression80 and self-controlling coping70 were associated with lower QoL.

Coping strategies were also identified as relevant mediator variables. Problem-focused, emotion-focused and stopping unpleasant emotion coping strategies were partial mediators between fatigue83 or type D personality84 and QoL as measured by the Mental Composite Score (MCS).

Other psychological factors

According to Van Damme et al,85 acceptance of the illness is a protective factor for QoL. The role of flexible adjustment and tenacious goal pursuit in achieving personally blocked goals was not as clear, although their findings showed a trend towards a positive relationship.

Resilience was confirmed as a protective factor of QoL in MS.27 86 Moreover, Koelmel et al87 highlighted its role as a mediator variable in the relationship between social support and MCS.

High levels of self-efficacy,51 88 self-esteem,88 illness identity88 and sense of coherence89 correlated with higher QoL, and self-esteem mediated in the relationship of social support with MCS.90 Ultimately, cognitive fusion, the extent to which people feel fused with or attached to their thoughts, mediated the relationship between stigma and QoL in MS.91

Social factors

Social support92 and participation93 were positively related with QoL. Several mediators in this relationship were mentioned above.

Demographic factors

Employment was found to be the leading sociodemographic factor influencing QoL. Several studies displayed an association between unemployment and lower QoL.30 34 54 67 94 Others showed a positive correlation between jobs adapted to disability,94 job match and job satisfaction,41 high employment status33 41 and QoL in MS. Low socioeconomic status35 and financial straits37 were also risk factors for lower QoL.

Brola et al30 31 noted that not having access to an adequate pharmacological treatment put QoL in danger. Congruent with this finding, Boogar et al35 found a positive treatment experience to be a protective factor.

Other sociodemographic variables related to poorer QoL in MS were male sex,37 old age,30 31 unmarried or living with significant others,37 whereas a higher education was a protective factor.33

Disease history

Some of the selected studies examined QoL in MS in its early years. According to Possa et al,95 QoL decreased in the first year of diagnosis, as assessed by the MCS and Physical Composite Score (PCS). Stern et al96 found the worst QoL in the youngest group of patients with MS .

Calandri et al97 found that during the first 3 years from diagnosis, problem solving and avoidance coping strategies had a positive effect on QoL. Nourbakhsh et al98 also studied factors influencing the development of QoL in the first 3 years. Their results showed that higher baseline levels of fatigue and depression predicted worse QoL as assessed by the PCS, whereas lower cognitive functioning and higher fatigue predicted a worse MCS.

Another study on QoL in MS by Buhse et al99 focused on old age. These authors identified neurological impairment, physical disability, depression and comorbidity with thyroid disease as risk factors for worse QoL as assessed by the PCS in a sample of elderly patients with MS. On the contrary, being widowed and employed were identified as protective PCS factors.

In a longitudinal study, Kinkel et al100 showed that a second clinical event consistent with clinically defined MS, higher EDSS at the time of diagnosis and an earlier MS onset predicted a decrease in PCS 10 years after diagnosis. Bueno et al101 also showed that progression from benign MS to non-benign MS predicted a decrease in PCS 25–30 years after diagnosis.

Some longitudinal predictors of QoL identified have been: longer MS duration predicted worse QoL 2 years later,102 and worse EDSS predicted worse QoL 2,102 6,103 and 10104 years later. Depression predicted worse QoL 6103 and 10104 years later, and stronger pain105 and cognitive impairment104 predicted worse QoL 10 years later.


Details of the selected articles on psychological intervention are presented in table 4.

Mindfulness-based therapies

All mindfulness-based therapy intervention programmes showed improvement in QoL at some evaluation point and at least in some QoL domains. Body-affective mindfulness intervention increased the general QoL score up to 6 months after treatment.106

Of the three studies on mindfulness-based stress reduction programmes, two showed a significant increase in QoL after treatment.107–109 One study109 only produced a small, insignificant increase after treatment and at the 3-month follow-up.

A community-based mindfulness programme resulted in a significant increase in MCS.110

Finally, mindfulness-based cognitive therapy did not show any significant difference in general QoL between the control and the experimental group; however, it did show significant differences in QoL: in health distress, mental well-being, role limitation due to emotional problems and cognitive performance.111

Cognitive behavioural

A wide spectrum of cognitive behavioural interventions was analysed.

In a study by Case et al,112 the experimental group attended 10 1-hour weekly sessions of healing light guided imagery. They found a greater increase in QoL in this group than with 10 hours of positive journaling in the active control group.

Blair et al113 focused intervention on emotion regulation. The design consisted of 16 1.5-hour biweekly sessions for 8 weeks. The intervention resulted in a significant increase in QoL 6 months after treatment.

Interventions by Calandri et al114 and Graziano et al115 had a comparable design. Participants were divided into two subgroups by age. Intervention comprised four to five 2-hour sessions over the course of 2 months, and one follow-up session 6 months after treatment. Calandri et al114 also included one follow-up session 12 months after treatment. At follow-up, the intervention groups in both studies had experienced an increase in QoL.

Three studies116–118 focused intervention on depressive symptoms. Kiropoulos et al116 and Chruzander et al117 found improvement in QoL at post-treatment and follow-up assessments. Kikuchi et al118 also found a post-treatment improvement, but not significant.

Two of the studies based intervention on acceptance and commitment therapy (ACT). Pakenham et al119 implemented an 8-week programme aimed at training in resilience. QoL increased at treatment end and at 3-month follow-up. Proctor et al120 implemented an 8-week intervention comprising telephone calls and self-help ACT books. No significant increase in QoL was observed.

Social and group support

The following social support and group interventions had an impact on QoL in MS.

Abolghasemi et al121 implemented a 12-session supportive–expressive therapy programme, which improved QoL.

Jongen et al122 tested an intensive social-cognitive wellness programme involving the partner or other significant informal caregiver. The results showed an increase in the MCS at 1, 3 and 6 months from treatment and in the PCS 6 months after treatment. The results of the programme were evaluated again 12 months after treatment. The relapsing–remitting MS group showed an increase in PCS and MCS.123

Eliášová et al124 found more improvement across several QoL domains in patients with MS after self-help group sessions than in patients who did not attend the self-help groups. Liu125 detected an increase in physical and psychological QoL in women with MS after participating in a hope-based group therapy programme for 1 hour twice a week for 8 weeks.

Symptom and self-management-based therapies

Two studies analysed a fatigue self-management group therapy. Mulligan et al126 reported positive, but not significant, changes in QoL after their treatment. Thomas et al127 reported significant positive changes in physical health assessed by the Multiple Sclerosis Impact Scale (MSIS-29) and vitality as measured by the SF-36 in the intervention group 12 months after the treatment.

In addition to fatigue self-management, Ehde et al128 focused in their intervention on pain and depression self-management. The results were compared with an educational programme. There was a higher QoL post-treatment and 12-month follow-up score in the self-management group. Feicke et al129 implemented a programme focused on MS self-management. As in Ehde et al,128 improvements in QoL were still maintained at 6-month follow-up.

Other psychological intervention

LeClaire et al130 implemented a 5-week positive psychology programme. The results showed only a significant improvement in the SF-36 vitality subscale.


First, the present systematic review was intended to identify risk and QoL protective factors in MS. The results showed that the EDSS was most employed for assessment of functional impairment.25–35 As expected, the number and severity of symptoms and associated impairment appeared to play a crucial role in QoL. Fatigue,28 29 39 40 42–52 cognitive impairment,39 50 52 53 63 66 67 and pain,35 39 50 51 55 56 in particular, were the focus of a large number of studies and were confirmed as important risk factors. Longitudinal studies suggested that greater fatigue,98 pain105 and cognitive impairment98 104 also predicted worse QoL up to 10 years later. This has important clinical implications, as treatment of the abovementioned symptoms should be prioritised. In general, functional impairment,102–104 as well as longer duration of illness,102 was predictor of QoL 2 to 10 years later, whereas disease progression101 from benign to non-benign MS predicted QoL as measured by the PCS up to 30 years later.

Among the emotional symptoms, there was convincing evidence that depression,28 29 32 34 35 39 40 51 55 66 69 71–75 along with depressive temperament77 and anxiety,38 40 51 69 71–74 76 were associated with lower QoL and that depression also predicted QoL up to 10 years later.104

The coping strategies applied obviously influenced QoL in MS, however their effect depended on the specific circumstances of the disease history. For example, problem solving and avoidance coping, normally classified as opposite strategies, both seemed to have a positive effect on the MCS in the first 3 years of diagnosis.97 However, in general, strategies associated with denial51 79 and avoidance of the challenges of the disease, such as problem avoidance,71 81 behavioural disengagement,51 80 distancing,81 self-distraction,79 social withdrawal71 and wishful thinking,71 were associated with a lower QoL. On the contrary, strategies based on acceptance and active commitment, such as active coping, humour, problem resolution, cognitive positive restructuring and emotional expression, led to higher QoL in MS.51 71 79–82 Obviously, there is a close connection between the active confrontation of the challenges of illness and specific personality-based convictions, such as a high self-efficacy. Thus, higher self-efficacy,51 88 self-esteem88 and sense of coherence89 improved QoL in MS.

Regarding sociodemographic influences on QoL, not surprisingly, unemployment, a low socioeconomic status35 and financial difficulties37 proved to be major risk factors.30 34 54 67 94 In keeping with the negative influence of the scarcity of resources, lack of access to therapy was also identified as a risk factor.30 31

The second aim of this systematic review was to study QoL in patients with MS at different times during their disease history. Two studies showed diminishing QoL in patients with MS in its early stage.95 96 This might have to do with the fact that patients being diagnosed with a severe chronic disease need a certain time to come to terms with this emotional shock. Oscillation between avoidance and problem solving, which both have a positive influence in the first 3 years after diagnosis,97 may be behind this inner struggle. In older patients, neurological impairment and physical disability,97 which represent the age-associated increase in physical impairment, were identified as risk factors for QoL in MS.

Finally, the third aim of this review was to analyse psychological interventions for the improvement of QoL in MS. Symptomatic improvement of psychopathology usually at the centre of psychotherapy outcome studies was not the primary focus of our review.131 Eight of the intervention studies specifically treated depressive symptomatology,106 110–112 115 117 118 either with mindfulness-based or cognitive behavioural approaches, both of which proved to be successful.

Three studies were specifically directed towards the treatment of fatigue112 126 127 by light guided imagery or self-management programmes. Both the imagery and self-management group intervention approaches were successful, whereas the individual self-management programme did not show significant improvement.

A variety of mindfulness-based approaches107–109 and a community-based intervention were directed at stress reduction.110 Three of the four studies showed some kind of improvement in QoL, including the only study with a control group.

Several of the interventions were designed to reinforce protective factors in patients with MS. Graziano et al115 focused on identity redefinition, sense of coherence and self-efficacy. Pakenham et al119 implemented a programme based on resilience training, and the programme by Blair et al113 focused on the improvement of emotional regulation. All of them were successful in improving QoL, confirming the alternative focus on protective factors instead of risk factors.

A wide spectrum of interventions based on social support concentrated on reinforcement of the social network of patients with MS, for example, self-help groups,124 hope-based group therapy,125 supportive–expressive therapy121 and social cognitive training with support partners.122 123 All interventions aimed at helping people overcome MS barriers in daily living by strengthening their social support, improving some aspects of QoL. This is consistent with the studies mentioned above92 93 and emphasises the importance of social support and participation as a protective factor for QoL.


The main limitation of this study was the impossibility of carrying out a quantitative synthesis of the results, due to the heterogeneity of methodologies and designs in the articles included. Due to the vast number of topics and limited resources, our search was restricted to a 5-year period through January 2019.


This review was intended to give a broad overview of QoL in MS. The findings show the importance of clinical, psychosocial and demographic variables as QoL risk and protective factors. A variety of psychological interventions ranging from mindfulness-based and cognitive behavioural approaches to self-help groups addressing these factors were identified as promising options for improving QoL. These findings have important clinical implications. A sound biopsychosocial assessment of patients with MS in daily clinical practice is necessary to ensure the possibility of early identification of QoL risk factors and evidence-based psychological intervention is recommended to improve or stabilise QoL.


Supplementary materials

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  • IG-G, AM-R, RC and MÁP-S-G contributed equally.

  • Contributors IG-G, AM-R, RC and MÁP-S-G contributed to conceptualisation, investigation, methodology, validation, writing original draft and writing review and editing.

  • Funding This study was financially supported by the program of Formation of University Professor of Ministry of Education, Culture and Sport of Spain grant number: FPU 17/04240.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No data are available. All data relevant to the study are included in the article or uploaded as supplemental information.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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