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, 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

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


  • Never tried medication for fatigue although I do battle it at times. Everyone is different so I know this probably isn’t for everyone, especially as MS presents lots of barriers, but fresh air really helps, and exercise, whatever that is and both are free and don’t involve feeling medicalised, which can be depressing in itself.

    • Tai chi, lifting weights, rowing machine and rest when needed. These have been my go to for fatigue and pain management. I’ve never taken drugs for fatigue, but my mom has. I wish she would follow my strategy.

  • Yoga and Tai chi are also good for
    MS fatigue, there’s been a few studies. These are movement meditations. Probably can add Pilates to this too.

  • Love this video!
    About Mindfulness, it takes Time. This was 6 minutes. Popping a pill 💊 takes a second.
    Writing a prescription is easier than explaining why you, the MS patient, should be grateful with a MonSter clawing at your life.
    Fatigue is invisible, annoying, frustrating. Can’t do what you used to. Couch lock 🛋
    I used modafinal when first diagnosed and working full time as a nurse.
    Eventually gave it up.
    It was like kicking a dead horse. Get up, get up!
    I’m using devices to help give me feedback Apollo Neuroscience wristband and Oura ring.
    My Brother calls it an Acoustic-ceutical 😎
    I don’t like pills and still I need what I take.
    Good to review med list at every doctor visit.

  • I am the father of a fairly newly diagnosed pwms and a consultant psychiatrist. Firstly, I would like to say that Mindfulness based therapy/practice isn’t really a complementary therapy but a mainstream therapy with a good evidence base for a range of psychiatric/brain/mind disorders so it doesn’t surprise me that it is helpful in fatigue – after all fatigue is largely a brain/mind symptom/experience. Secondly, I am well aware of the role that anxiety and stress have on the emergence or attention to somatic symptoms and how this seems to play out in the awareness of new or old ms symptoms – Mindfulness practice is in my view more effective than medication in managing stress and many forms of anxiety. Thirdly, I can reflect on the really important contribution that Mindfulness practice has had (in addition to medication) on my recovery from a recent (and first) episode of moderately severe depressive illness. Gratitude is a central concept in Mindfulness practice and has been called a “superpower” for managing a whole range of negative aspects of life. More recently I have learned of the importance of “care” in Mindfulness practice in the sense of taking care in whatever we do. I think this should be a valuable lesson/reminder for clinicians of the importance of taking care in everything we do for and every interaction we have with our patients.

  • Mindfulness helps me from going crazy or sliding in depression. I heartily recommend Sam Harris Waking up for an app without all the new age stuff that chased me away from meditation prior to starting with it.

    Like exercise, it needs determination to get started.

    As for stacks upon stacks of meds, decidedly not my experience. If anything, at some points way too little (hellish headaches for days after LP that would definitely have been a case for opioids, for one – instead, ‘just double the paracetamol’). In general in my experience pain management is weird, if you have more pain than they expect they won’t give you stronger meds without a fight and if less, expect you to still take big doses of whatever they have on their list.

    Aside of that, I have to ask for stuff and then sometimes clearly get skepticism for drug seeking because a lot of the things that actually do work also have substantial abuse potential. At least my current GP is relatively relaxed when it comes to non-habit building most meds (I really don’t want to imagine what a sildenafil refill would have been like with the previous one).

    • I might add that the cynicism regarding mindfulness likely to no small part stems from the lack of compliance HCPs expect from patients – much like with healthy eating and exercise where the benefits are actually more immediately obvious than with mindfulness.

  • And on the topic of the post, I am very grateful to have found this blog during the initial weeks of the Covid pandemy when information was very sparse (MSIF and local MS society were barely useful). Definitely helped me not to lose my mind.

    So thank you very much, especially ProfG and MD but also to the other contributors! Merry Christmas!

  • There are other forms of meditation out there that are a lot easier than mindfulness, especially for people new to meditation.
    Mindfulness is a form of focused attention and in ways concentration.

  • I was fortunate enough to attend a Fatigue Management course at my local MS Centre – it was invaluable. My biggest problem was adjusting my life to accommodate my fatigue and this course taught me that I could no longer remain the control freak that I was but had to learn to prioritise, pace myself and delegate to others. It also taught me to make sure I keep back enough stamina to do the things that I enjoy and not waste it all on unfulfilling work. It was positively life changing.

  • I can’t speak to any studies or clinical trials, only my own experience. I’ve been diagnosed with MS for 6 years, though it appears I’ve had it much longer. I had 8 oligoclonal bands in my CSF at time of diagnosis, and my first huge, noticeable flare was incapacitating vertigo and ataxia from a pontine lesion. I have a wide array of sensory issues that are worsening with time, and beginning to have some motor involvement. My neurologist feels I’ve crossed the threshold into SPMS. I am on my fourth treatment, Tysabri, having failed off-label LDN, Copaxone, and Ocrevus. But, I’m still working full time, still able to care for myself, and still doing my best to remain functional for as long as I can. The single most important aspect of my “treatment” is the ability to be resilient. And resilience includes adaptability, as well as some degree of surrender. I was riding my bike 100 miles per week in the beginning. I can still ride, but not nearly as far. Through mindfulness practices, I’ve been able to cultivate that sense of resiliency that leads me to other things my body can still do (like yoga), as well as be able to gently let go of the things I can do no longer. I live in the U.S., and medications are actively marketed and are one of the many tiers of consumerism here. It’s remarkably sad. We aren’t taught how to carry a thing like incurable illness and loss, only how to take a pill, or a shot, or an infusion. If pwMS and chronic illness were given an arsenal of mindfulness tools to employ as they navigate a life that is not ideal, but is a gift nonetheless, I think quality of life would improve drastically.

  • No noticeable improvement in 6 weeks?
    How did any any of these drugs become accepted treatments for fatigue?
    I’m guessing previous studies showed an effect?
    What portion of MS patients report improvement in symptoms after 6 weeks on a DMT?
    I know, not a valid comparison since all we ask of the DMT is for some possible slowdown of disability.
    There are loads of drugs that are known to work well on fatigue.
    A whole class of drugs! (Stimulants) Amphetamines, even some opioid drugs help.
    Cocaine works great even in low doses, but has the unfortunate side effect of causing a vast improvement in most patients sense of well being.
    Don’t tell anyone, but I’m taking low dose caffeine every morning.
    I know it can have adverse effects. I think probably it’s biggest problem is that it’s too old, inexpensive, and unpatentable..

    Love this blog,
    Thank you very much.
    Merry Christmas,
    Joyous Festivus,
    Happy holidays etc.

  • I’m medication averse but I also appreciate that I’m NEDA so I don’t need meds. I take nothing else; no prescription meds, no over the counter meds and no supplements. I would if I had to, as for instance, in the case of an infection. It doesn’t mean I have never needed to take a course of medication but I’m off them as soon as I safely can. I find my very close (immersive) connexion with the natural world provides me with the equivalent of a mindfulness experience.

  • Gratitude and being present in the moment are paramount, whether one has an illness, injury, or blessed with perfect health. I am grateful for many things, including this blog, and the virtual community on it. I wish you all a happy holiday and a healthy very wonderful brand new year!

  • Thanks Prof G, for bringing up a very important subject.

    I follow Vipassana Meditation – which is one of the oldest and most widely practiced non-sectarian meditation technique. I attended a 10-day Vipassana retreat that taught me the practice. Vipassana centers are all over the world; it costs nothing (free boarding and lodging) – except a commitment of 10 days of one’s lifetime. I would recommend the practice for anyone for a happier life.

    I practice Vipassana for about an hour every morning and then a little bit before I fall asleep.

    I was diagnosed in 2013. Started on Tecfidera and after several relapses switched to Ocrevus in 2017. I have had 2 further relapses since being on O – most recent was 10 days ago.

    I have had trouble with Fatigue from the very beginning but luckily I didn’t resort to any any meds. I take Ampyra for my walking other than my Vit D. That’s pretty much it.

    Now, coming to the technique itself, I feel that this maybe very different from the mindfulness practice that is widely practiced today. This practice trains your mind to observe your bodily sensations and to stop reacting to the same. Yes, it is hard but not impossible – hence a technique that one should practice every day. With practice one can quickly observe and recognize gross sensations such as pain, discomfort, fatigue etc. From birth, we are tuned to react to these sensations. But the practice helps one to observe and to remain equanimous to these sensations. From an MS standpoint, I quickly came to the realization that a loss of sensation is itself a sensation.

    The technique goes beyond handling gross sensations – the existence of subtle sensations – but that’s a different story.

  • I was taking 100mg of modafinil each morning to treat my fatigue for many years…at least 15. I thought it gave me some benefit. However, after reading this study I stopped taking it. Guess what? I’ve now been off it for one month and I don’t see any difference in my fatigue level.

    Exercise and getting eight hours of sleep, when possible, help a lot more than this medication.

By Prof G



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