Barts-MS rose-tinted-odometer: ★★★★★
A problem in modern medical practice is the assumption that there is a pill for everything. The one eye-opener for me after my recent trauma has been how easy it is for medics to reach for the prescription pad. When I was first discharged from hospital I was on 14 different medications. About half of the medications were prescribed to manage or prevent the side effects of the primary medications. It is easy to rationalise the use of each of the 14 medications, but were they all necessary? It is quite astounding how we have ‘pharmaceuticalised medicine’.
Initially, when my head was muzzled by morphine and gabapentin, I had an elaborate system in place to make sure I didn’t miss or forget any of my medications. This experience has given me a profound appreciation for how difficult it must be for some of my own patients, particularly those with cognitive impairment, to manage their own polypharmacy. The other question, which is the elephant in the room, is are all these medications really necessary.
A good example in MS is the management of MS-related fatigue. MS neurologists prescribe a large number of different medications for MS fatigue when in reality none, yes zero, of these medications has been shown to make a difference in randomised controlled trials. A recent study from the US shows that amantadine, modafinil and methylphenidate make no difference. In comparison, mindfulness therapy has been shown to work in several MS fatigue trials. So why don’t neurologists prescribe mindfulness to more of their patients? There is also an expanding evidence-base that mindfulness therapy helps depression, anxiety and insomnia.
Maybe 2021 should be the year when the medical profession questions and challenges the ‘pharmaceutical-model of medicine’ and helps lobby the NHS so that all of our patients have access to mindfulness therapy.
If you have a moment can I suggest you watch Gratitude, on the ‘Mindfulness 360 – Center For Mindfulness’ channel on YouTube. Are you surprised that this is better than a tablet?
I would be very interested if you could share your thoughts on this blog post and your own experiences with tablets versus mindfulness therapy for managing your symptoms. There are a lot of cynical HCPs out there who question the benefits of mindfulness, which is just one of the main barriers that prevent the wide adoption of this complementary therapy into routine MS practice.
Nourbakhsh et al. Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial. Lancet Neurol. 2021 Jan;20(1):38-48.
Background: Methylphenidate, modafinil, and amantadine are commonly prescribed medications for alleviating fatigue in multiple sclerosis; however, the evidence supporting their efficacy is sparse and conflicting. Our goal was to compare the efficacy of these three medications with each other and placebo in patients with multiple sclerosis fatigue.
Methods: In this randomised, placebo-controlled, four-sequence, four-period, crossover, double-blind trial, patients with multiple sclerosis who reported fatigue and had a Modified Fatigue Impact Scale (MFIS) score of more than 33 were recruited at two academic multiple sclerosis centres in the USA. Participants received oral amantadine (up to 100 mg twice daily), modafinil (up to 100 mg twice daily), methylphenidate (up to 10 mg twice daily), or placebo, each given for up to 6 weeks. All patients were intended to receive all four study medications, in turn, in one of four different sequences with 2-week washout periods between medications. A biostatistician prepared a concealed allocation schedule, stratified by site, randomly assigning a sequence of medications in approximately a 1:1:1:1 ratio, in blocks of eight, to a consecutive series of numbers. The statistician and pharmacists had no role in assessing the participants or collecting data, and the participants, caregivers, and assessors were masked to allocation. The primary outcome measure was the MFIS measured while taking the highest tolerated dose at week 5 of each medication period, analysed by use of a linear mixed-effect regression model. This trial is registered with ClinicalTrials.gov, NCT03185065 and is closed.
Findings: Between Oct 4, 2017, and Feb 27, 2019, of 169 patients screened, 141 patients were enrolled and randomly assigned to one of four medication administration sequences: 35 (25%) patients to the amantadine, placebo, modafinil, and methylphenidate sequence; 34 (24%) patients to the placebo, methylphenidate, amantadine, and modafinil sequence; 35 (25%) patients to the modafinil, amantadine, methylphenidate, and placebo sequence; and 37 (26%) patients to the methylphenidate, modafinil, placebo, and amantadine sequence. Data from 136 participants were available for the intention-to-treat analysis of the primary outcome. The estimated mean values of MFIS total scores at baseline and the maximal tolerated dose were as follows: 51·3 (95% CI 49·0-53·6) at baseline, 40·6 (38·2-43·1) with placebo, 41·3 (38·8-43·7) with amantadine, 39·0 (36·6-41·4) with modafinil, and 38·6 (36·2-41·0) with methylphenidate (p=0·20 for the overall medication effect in the linear mixed-effect regression model). As compared with placebo (38 [31%] of 124 patients), higher proportions of participants reported adverse events while taking amantadine (49 [39%] of 127 patients), modafinil (50 [40%] of 125 patients), and methylphenidate (51 [40%] of 129 patients). Three serious adverse events occurred during the study (pulmonary embolism and myocarditis while taking amantadine, and a multiple sclerosis exacerbation requiring hospital admission while taking modafinil).
Interpretation: Amantadine, modafinil, and methylphenidate were not superior to placebo in improving multiple sclerosis fatigue and caused more frequent adverse events. The results of this study do not support an indiscriminate use of amantadine, modafinil, or methylphenidate for the treatment of fatigue in multiple sclerosis.
Ulrichsen et al. Clinical Utility of Mindfulness Training in the Treatment of Fatigue After Stroke, Traumatic Brain Injury and Multiple Sclerosis: A Systematic Literature Review and Meta-analysis. Front Psychol. 2016 Jun 23;7:912. doi: 10.3389/fpsyg.2016.00912. eCollection 2016.
Background: Fatigue is a common symptom following neurological illnesses and injuries, and is rated as one of the most debilitating sequela in conditions such as stroke, traumatic brain injury (TBI), and multiple sclerosis (MS). Yet effective treatments are lacking, suggesting a pressing need for a better understanding of its etiology and mechanisms that may alleviate the symptoms. Recently mindfulness-based interventions have demonstrated promising results for fatigue symptom relief.
Objective: Investigate the efficacy of mindfulness-based interventions for fatigue across neurological conditions and acquired brain injuries.
Materials and methods: Systematic literature searches were conducted in PubMed, Medline, Web of Science, and PsycINFO. We included randomized controlled trials applying mindfulness-based interventions in patients with neurological conditions or acquired brain injuries. Four studies (N = 257) were retained for meta-analysis. The studies included patients diagnosed with MS, TBI, and stroke.
Results: The estimated effect size for the total sample was -0.37 (95% CI: -0.58, -0.17).
Conclusion: The results indicate that mindfulness-based interventions may relieve fatigue in neurological conditions such as stroke, TBI, and MS. However, the effect size is moderate, and further research is needed in order to determine the effect and improve our understanding of how mindfulness-based interventions affect fatigue symptom perception in patients with neurological conditions.
Simpson et al. Effects of Mindfulness-based interventions on physical symptoms in people with multiple sclerosis – a systematic review and meta-analysis. Mult Scler Relat Disord. 2020 Feb;38:101493.
Background: Physical wellbeing is commonly impaired in people with multiple sclerosis (PwMS). This study aims to update our previous systematic review (2014) and conduct a meta-analysis on the efficacy of Mindfulness-based interventions (MBIs) for improving physical symptoms in PwMS.
Methods: In November 2017 we carried out systematic searches for eligible randomised controlled trials (RCTs) in seven major databases, updating our search in July 2018. We used medical subject headings and key words. Two independent reviewers used pre-defined criteria to screen, data extract, quality appraise, and analyse studies. The Cochrane Collaboration risk of bias tool was used to determine study quality. Physical wellbeing was the main outcome of interest. We used the random effects model for meta-analysis, reporting effect sizes as Standardised Mean Difference (SMD). This study is registered with PROSPERO: CRD42018093171.
Results: We identified 10 RCTs as eligible for inclusion in the systematic review (including 678 PwMS), whilst seven RCTs (555 PwMS) had data that could be used in our meta-analyses. In general, comorbidity, disability, ethnicity and socio-economic status were poorly reported. MBIs included manualised and tailored interventions, treatment duration 6-9 weeks, delivered face-to-face and online in groups and also individually. For fatigue, against any comparator SMD was 0.24 (0.08 – 0.41), I2=0%; against active comparators only, SMD was 0.10 (-0.14 – 0.34), I2=0%. For pain SMD was 0.16 (-0.46 – 0.79), I2=77%. Three adverse events occurred across all studies.
Conclusions: MBIs appear to be an effective treatment for fatigue in PwMS. The optimal MBI in this context remains unclear. Further research into MBI optimisation, cost- and comparative-effectiveness is required.
Crowdfunding: Are you a supporter of Prof G’s ‘Bed-to-5km Challenge’ in support of MS research?
CoI: multiple
Twitter: @gavinGiovannoni Medium: @gavin_24211