Mindfulness based interventions in multiple sclerosis - a systematic review

Mindfulness practices originate from ancient Buddhist meditation techniques, but have since been secularised, manualised, and appropriated for use in a diverse range of clinical settings. Jon Kabat-Zinn, who introduced Mindfulness techniques to the West in the nineteen eighties, has defined Mindfulness as: ‘..paying attention in a particular way: on purpose, in the present moment, and nonjudgementally’ [25]. The original research studies on Mindfulness focussed on chronic pain, but Mindfulness-based interventions (MBIs) have become increasingly popular in various areas of chronic disease management over the last 30 years. Group-oriented, Mindfulness Based Stress Reduction (MBSR) is the most well researched MBI approach and has been applied in the management of: anxiety, chronic pain, depression, and stroke [26‐29]. MBSR appears to have neuroendocrine, immunological and neuroplastic effects, although research in this area remains explorative in nature [30‐33]. MBSR classically consists of instruction in three meditation techniques, namely breath awareness, body awareness, and dynamic yoga postures (mindful movement) [34] taught in groups over 8 weeks. Mindfulness Based Cognitive Therapy (MBCT) is a derivative of MBSR, with a greater emphasis on cognitive techniques, designed for specific mental health conditions such as recurrent depression [35].

The mitigation of stress is proposed as a means to actively manage and reduce pathological disease activity in people with MS [22]. Indeed, a CBT intervention has already demonstrated efficacy, reducing gadolinium lesion enhancement on neuroimaging during the active period of treatment. However, this effect is not sustained on cessation of therapist input [22]. MBIs are thought to operate in a different manner to CBT [36] and might have a more sustained effect, given the strong emphasis on regular self-practice. To date and as far as we are aware, no systematic review of the evidence for MBIs in people with MS has been published. This paper aims to evaluate the effectiveness of MBIs in people with MS.

In May 2013 a systematic search for published and unpublished studies was conducted in six major electronic bibliographic databases: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine Database, and PsycInfo. To identify any additional published and/or unpublished trials, we also searched ProQuest Dissertations & Theses Database and contacted MS/mindfulness researchers. Selected medical subject headings were combined with key words relating to MS and mindfulness to create a search strategy which was finalised for use in MEDLINE (see Additional file 1) and amended for use in the other databases, using appropriate controlled vocabulary, Boolean operators, and search symbols. Delimiters were: dates searched (1980–2013); research subjects (human); and language (English). The search included the grey literature, using reference lists and citation searching from reviews and published trials, the Science Citation Index, and also involved consulting noted experts in the field. Endnote was used to store and manage the results of the database searches.

Studies were selected for inclusion using criteria related to the Study design, Participants, Interventions, and Outcomes model (SPIO). SPIO is an adapted version of PICOs (Population, Interventions, Comparison, and Outcomes) [37]. Any definite diagnosis of MS in an adult (>18 years) was acceptable for inclusion in the review. MBIs can vary by both name and range of ingredients; therefore a core content of: breath awareness, body awareness, and mindful movement, comparable to that of the standardized MBSR, was decided upon as a pre-requisite for inclusion. MBSR was chosen as it represents the original model introduced by Jon Kabat-Zinn in the nineteen eighties, which has been widely described and researched since its inception. Perceived stress was the primary outcome measure sought. Secondary outcome measures included: mental health, physical health, psychosocial measures, as well as health care utilisation.

The bibliographic records identified by the searches were screened for relevance using broad inclusion criteria, i.e. ‘multiple sclerosis’ and ‘mindfulness’. All relevant papers were then screened, using the SPIO inclusion criteria (Table 1), to select eligible papers. All selected papers were subject to methodological appraisal. As the search yielded low numbers, a decision was made not to exclude studies solely on the basis of poor methodological quality. Screening methods were based on the Systematic Reviews guidance outlined in the Centre for Reviews and Dissemination (CRD) [38]. Methodological issues are discussed below and reported in the evidence table (Table 2).

Risk of bias was assessed using the Cochrane Collaboration’s assessment tool [39] to summarise the risk of bias for major outcomes. The evidence for each individual outcome was graded as low, unclear, or high risk. This included assessing for evidence of: sequence generation; allocation concealment; blinding of participants, personnel and outcome assessors; incomplete outcome data; selective outcome reporting; and any other sources of bias.

The authors developed a data extraction tool, adapted from a previous systematic review examining the benefits of MBIs following transient ischaemic attack and stroke [29]. The data extracted included information on study design and methodology, the populations under review, the interventions being employed, and the outcomes recorded in each study. Two reviewers working independently carried out screening and data extraction. Broad screening was undertaken by RS and SB; narrow screening by RS and JB. Any disagreements were adjudicated via a further reviewer (SM).

As the results of the search and review were heterogenous, findings are presented in a narrative format. It was not possible to undertake a meta-analysis.

The three studies originated from Wales (Mills and Allen [41]), Switzerland (Grossman et al. [40]), and the United States (Tavee et al. [42]). Grossman et al. [40] and Mills and Allen [41] conducted randomised controlled trials (RCT), while Tavee et al. [42] reported a non-randomised controlled trial. None of the studies compared MBIs against an active intervention. Grossman et al. [40] recruited from Neurology out-patients, and conducted the study in a university hospital setting, as did Tavee et al. [42]. Mills and Allen [41] recruited from a mixture of General Practitioner and Physiotherapist referrals.

Across the studies, there was a total of 183 participants. Attrition was variable. Grossman et al. [40] described remarkably low attrition rates (5%) and a high attendance rate (92%), whilst Mills and Allen [41] reported drop out rates of 12.5% and cited reasons such as bereavement and dislike of Tai Chi style exercises. Tavee et al. [42] had the highest attrition of all (43%), and cited issues such as transportation and a lack of interest.

Tavee et al. [42] presented results for a mixed study population i.e. people with MS and patients with Peripheral Neuropathy. As we were unable to obtain MS-only data, this limited interpretation of their findings. Grossman et al. [40] collected data at 3 points (pre- and post- intervention, and at 6-month follow up), while Mills and Allen [41] recorded data at pre-, post- and 3 months after the intervention. Tavee et al. [42] only recorded data at pre- and immediately post-intervention. See Table 2 for details.

Grossman et al. [40] delivered an intervention closely mapped to MBSR. Mills and Allen [41] and Tavee et al. [42] used less standardised versions, introducing elements of Tai Chi and Qi Gong. However, all three studies were broadly comparable in content, with all three emphasising mindful breath awareness, mindful movement, and body awareness or ‘scanning’. The MBIs were group based in 2 of the studies, but the Mills and Allen [41] intervention was delivered one to one.

Grossman et al. [40] used certified and experienced MBI teachers to deliver the MBI over 8 weekly 2.5 hour sessions, with a 7 hour session at week 6. They emphasised mindfulness practices in the sitting, lying and yoga asana postures, and also encouraged ‘homework’ practices for 40 minutes daily. They were the only investigators to record homework practice times. Tavee et al. [42] delivered a 4 hour introductory group session, followed by 8 weekly 1.5 hour classes, with a Buddhist Monk teaching all of the course components, including Samatha meditation (sitting and observing the breath), and mindful movement in the form of Tai Chi/Qi Gong and walking meditation. Tavee et al. [42] encouraged home practice, but did not record frequencies. Mills and Allen [41] delivered six individualised sessions in which unspecified teachers taught mindful movement with Tai Chi/Qi Gong, with breath and posture awareness, whilst encouraging participants to cultivate compassionate feelings towards themselves. Mills and Allen [41] also provided self study material, but did not report on participant uptake and usage by participants. Please see Table 2.

None of the studies provided data regarding ethnicity of participants. Across the three studies, 80% (n = 146) of participants were female, and the mean (SD) age of the total sample (n = 183) was 48.6 (9.4) years. Data regarding socioeconomic status was generally not well reported; for example, Mills and Allen [41] provided data on only half of their study population, of whom, 50% were in employment. Grossman et al. [40] recorded number of years in education. Disease phenotype was described in two of the studies; however, Tavee et al. [42] simply described participants (n = 17) as having any diagnosis of MS. From the remaining 166 patients where a phenotype could be discerned, 123 (67%) had a diagnosis of relapsing remitting MS, and the other 43 (25%) were diagnosed with secondary progressive MS. All three studies excluded patients with significant cognitive impairment, as well as those with severe physical disability, according to either the Expanded Disability Status Scale being >6 (requiring 2 walking aids i.e. a pair of canes, crutches, etc. - in order to walk about 20 meters, without resting), or more generally, being unable to make their own way to the hospital (Mills and Allen [41]). See Table 3.

The primary outcome sought by this review (perceived stress) was not reported in any of the studies. However, secondary outcomes of interest included: anxiety, depression, HRQOL, concentration, fatigue, vitality and general wellbeing. No information was available on economic parameters, such as cost/benefit analysis for patients, or health service utilisation. Please see Table 2.

Quality was assessed using the Cochrane Collaboration tool for Risk of Bias [39]. Of the 3 studies, only Grossman et al. [40] adequately describe evidence of sequence generation at the randomisation stage. Allocation concealment was most convincingly implemented by Grossman et al. [40], where the investigator was fully blinded to patient information, but this was not clearly described by Mills and Allen [41]; Tavee et al. [42] appear to have collected a control group independently of those expressing a desire to take part in the intervention group. Only Grossman et al. [40] described blinding of outcome assessors. All three authors described incomplete outcome data, including attrition rates, but only Grossman et al. [40] included this intention to treat and attrition data in the statistical analysis. There was no substantive evidence for selective outcome reporting in any of the studies, although Mills and Allen [41] omitted data on mood recording via Profile of Mood States (POMS), which is described elsewhere [43]. Overall, only the study by Grossman et al. [40] can be considered of high methodological quality (see Table 7).

This review employed a rigorous methodological strategy to search and appraise the research literature involving MBIs in people with MS. Three reviewers were involved in the screening and appraisal of studies suitable for inclusion, with further discussion taking place, as required. Quality was assessed in accordance with the Cochrane Collaboration guidance.

The fact that MBIs originate from ancient oriental traditions may bias the results, in that, due to resource constraints, our review was limited to papers published in English. The low methodological quality of two studies, and the overall heterogenous nature of the studies, precluded quantitative meta-analysis.

Grossman et al. [40] produced a well designed RCT, with adequate numbers being included to allow power calculations. Their strict inclusion/exclusion criteria, and widely recognisable form of MBI, delivered by experienced, certified trainers, with pre-post and three-month follow up measures being collected, allows a degree of confidence when reviewing their findings. Mills and Allen [41] and Tavee et al. [42] conducted studies that were of lower methodological quality, with small sample sizes, and less well-defined intervention standards. There was no randomisation employed by Tavee et al. [42]. Comparing all three studies, there is considerable heterogeneity with respect to populations, interventions and outcome measures, and almost no meaningful information on the effects on different socioeconomic groups. Limited information was provided regarding different disease phenotypes and ‘stages’ of illness. Furthermore, little evidence is available about economic costs/benefits of the MBIs in this group, making drawing conclusions about any individual MBI technique in this population in general problematic. As such, these results should be treated with caution.

Future studies of MBIs in people with MS should be of a larger scale, employing robust methodological techniques. They should examine physical and psychological measures; different disease phenotypes, at various defined stages of disease progression, of varied functional status; and should address important questions around feasibility, acceptability and appropriateness in diverse ethnic groups; as well as economic concerns such as health care utilisation and cost effectiveness. For specialist groups, such as people with MS, it may be worth examining whether having classes run by specialist trainers’ (i.e. health professionals) rather than ‘generic’ MBI trainers has any specific advantages/benefits.

Correlating findings with neuropsychological, biomarker and clinical imaging evidence would also be very informative. Given the widely varying attrition rates reported, qualitative research should also be employed to gather information on the broad acceptability of MBIs from the perspective of people with MS. Such research could also explore perceived stress and self-efficacy, as discussed previously.

MBIs may have utility in the MS clinical population, particularly for mental health conditions, such as anxiety and depression, as well as physical function. There is no overt evidence of harm.