What is your ACB?

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ACB = anticholinergic burden

Barts-MS rose-tinted-odometer: ★

“I had no idea oxybutynin and other anticholinergics affected cognition to such an extent” is the standard response I get when I discuss the impact of the most commonly prescribed drugs for MS-related bladder problems (urgency and frequency). The older the bladder drug the more likely it is to cross the blood-brain barrier and affect cognition. Oxybutynin, for example, reduces IQ or cognition by a half a standard deviation, or approximately 7 points on the standardised IQ scale. Although I stopped prescribing oxybutynin decades ago it is often still prescribed.

And it is not only common bladder medications that have anticholinergic effects the list, which is long, also includes tricyclic antidepressants and over the counter anti-histamines. Tricyclic antidepressants are often prescribed to help pwMS with pain and are used as sedatives. It is remarkable how often neurologists and pain doctors reach from the prescription pad to prescribe amitriptyline to their patients. I think it is time for us to step back from this practice as we now have other options or better medication with less off-target anticholinergic effects. 

It is also worth noting that exposure to anticholinergics increases your risk of developing dementia. There have been several population case-control studies showing this. As MS affects cognition I suspect the MS brain is more vulnerable to the effects of anticholinergics and hence we may have inadvertently been exacerbating MS dementia. It is time for us to reevaluate how we manage bladder dysfunction and other symptomatic problems in MS and avoid prescribing drugs with anticholinergic effects. 

The study below compared a relatively new class of drug represented by mirabegron that works on the so-called beta-3 adrenergic receptor and showed it was as effective as anticholinergic drugs in controlling bladder symptoms in MS. However, as it is a newer drug it is more expensive than the commonly prescribed anticholinergics and GPs, therefore, are often reluctant to prescribe mirabegron. The question I ask is if they had MS and bladder dysfunction, which agent would they like to be on. I bet mirabegron would be their choice. ‘Prescribe for your patients what you would want to be prescribed to you’ is a maxim that should be commonly used by doctors.

Anticholinergics also make MS-related constipation worse and cause dryness of the mouth that is often the most common adverse effect that causes patients to stop taking their medication. 

Another trend has been the off-label prescribing of anticholinergic agents to promote remyelination, in particular, the drug clemastine. The clinical data on clemastine is at present rather weak and we need to wait for further trials to try and confirm preliminary results in pwMS. In addition, you may not need to take clemastine for prolonged periods of time to promote remyelination as once the demyelinated areas are remyelinated the drug could theoretically be stopped. So I don’t advocate the off-label use of clemastine or benztropine, another remyelinating anticholinergic, in pwMS because of the downside of cognitive impairment for questionable benefits in relation to remyelination. 

Can I suggest you review your symptomatic medications and ask yourself what your anticholinergic burden (ABC) is and if it is high you should review your medication with your MS team to see if anything can be done to reduce the burden on your brain? There is an online ACB (anticholinergic burden calculator)  that makes this task relatively easy and provides you with a risk score. Although this calculator was created for confusion, falls and death in the elderly it is still useful to give you an idea of your anticholinergic burden. Any score of 3 or higher is undesirable. 

I would be interested to know if any of you have stopped taking and anticholinergic and noticed an improvement in your cognition? 

Glykas et al. B3 agonists or anticholinergics in the treatment of the lower urinary tract dysfunction in patients with multiple sclerosis?-A randomized study. World J Urol. 2021 Jan 2. doi: 10.1007/s00345-020-03555-8. 

Introduction and objective: Multiple sclerosis (MS) is the most frequent autoimmune demyelinating disease of the central nervous system. MS patients usually present with lower urinary tract dysfunction (LUTD). Objective of this study is to evaluate and compare the efficacy and safety of treating MS patients with LUTD with either a b3 agonist (mirabegron) or anticholinergics. The study’s primary outcome is the LUTD symptom improvement.

Material and methods: This is a multi-center, single-blinded, comparative study including 91 MS patients with LUTD. At baseline, patients underwent thorough clinical examination, urine cultivation and abdominal ultrasound and completed urination diaries and specific, validated questionnaires (NBSS, MusiQoL). At second visit, patients were administered either mirabegron or anticholinergics. Treatment was always carried out alongside with MS treatment. Reevaluation was performed 3 months after first visit. Patients underwent the same clinical and imaging tests that were carried out at first visit.

Results: We compared several clinical and imaging parameters between the two groups at first visit and month 3 after treatment. Νo statistical difference was noted between the mirabegron group and the anticholinergic group in terms of LUTD improvement. In both groups, improvement from baseline regarding LUTD was recorded. Statistical analysis was performed using the paired and unpaired t test method. No patient discontinued either medication due to side effects.

Conclusions: MS patients receiving either mirabegron or anticholinergic therapy for LUTD showed improvement. Nevertheless, no statistical difference was noted between the two cohorts at 3 months in terms of drug efficacy in all the statistically significant parameters.

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.

26 comments

  • ‘Prescribe for your patients what you would want to be prescribed to you’ is a maxim that should be commonly used by doctors.
    Yes, my understanding is that GP’s will prescribe the cheapest drug first, then change to a more expensive drug, if the first drug works out unsuitable. Is this similar for hospital doctors?

    • Yes and no. If you show the more expensive drug is more cost-effective then it gets prescribed. This is why NICE was formed to make these value judgements.

    • Not outside of a clinical trial unless you take one of the DMTs with anti-EBV effects, for example, anti-CD20 therapies and possibly teriflunomide.

      • I wonder how did she manage to get it though ?

        https://pubmed.ncbi.nlm.nih.gov/29510325/

        Title : Could antiretrovirals be treating EBV in MS? A case report

        In the text it is mentioned she independantly started it and that she was a student.

        The patient, a medical student, after reading a case report of MS with sustained resolution of symptoms on HAART5, independently started therapy with Combivir (zidovudine 300mg/lamivudine 150mg) twice daily.

        Any thoughts on how she managed to obtain it ?

        • I brave and pioneering neurologist prescribed it. This is how innovation used to happen in the past and now, at least in the UK (this patient was managed in the USA) we have our hands tied by red tape.

        • The work of antiretrovirals does not prove EBV theory, but rather the HERV theory (or at least their interaction).

          Generally, having many licenced drugs for the disease makes it less likely to get an off label prescription.
          (Also, the patient in this paper was a student doctor, so probably knew how to get the prescription she needed.)

  • Something everybody needs to be aware of is that, although it is sold as a food supplement, CBD oil adds to the anticholinergic burden. So if you’re already taking prescribed oxybutynin and a tricyclic and you add over the counter CBD and antihistamines, your anticholinergic load becomes really high.

    • It is one of the newer generation H1 blockers that is designed not to cross the blood-brain-barrier and it has very few if any anticholinergic effects. So yes it is one of the safer anti-histamines.

  • Prof, this is a poignant thread for me as i have recently weaned myself off amitriptaline (10mg) following one of your earlier posts. I was offered gabapentin instead to control sensory issues and spasms / twitches. To be honest, it has made me feel worse but when i tried to stop it all together, i became quite anxious (minor withdrawal? i was only on a low 100mg dose at night). I did feel better on the amitriptaline and it almost guaranteed a reasonable nights sleep so was considering going back to my previous low dose. Is there an alternative i could be considering? i read that Barts were trying to develop a drug for spasms / spacticity but couldnt see that anything came to fruition. I’m know that you do not give personal advice but it would be useful to understand the alternatives that are available if trying to avoid anticholinegics. The sad reality for me and most others is that the nurse wont have an answer to this and the consultant is impossible to access

    • Instead of amitriptyline for pain, I tend to now use duloxetine (atypical SSRI) that has far fewer anticholinergic effects and I am not aware of it causing cognitive problems. Importantly duloxetine is licensed for pain.

      • Thank you Prof. I have to say that i am not actually in pain, or at least what i would consider to be pain. Tingling, pins and needles, numbness yes but they are more annoying, aggitating symptoms than painful. I do get confused a little as to whether these sensations fall under the umbrella of ‘pain’ in MS land

      • Anon, have you tried exercise for spasms?
        It works for me, I don’t use medication. Even one of those £15 pedal exercisers, from mobility shops could possibly help. We can use it at home, the pedal exerciser can be used for arms too, on a table. Walking helps me too with spasms.

  • A great article that made me stop and look at my daily general medicines cocktail. I ran the ACB test and came out with a score of 12! I am now querying whether there are better med options for controlling my MS symptoms with my MS team. David

  • Sorry prof. G if I ask you a question that has little to do with this topic: I am anxiously waiting for your idea on what is the best vaccine to take for me who have MS and I take Tysabri every 6 weeks.
    Better Pfizer / Moderna (without knowing long-term effects on pwMS) or Astra zeneca (perhaps more tested but with two cases of transverse myelitis)? Will you make a table in the future on which is the best vaccine for pwMS based also on the dmt drugs they are making?
    Thank you

    Massimo

    • The long term effects of none of the vaccines are known, but to date millions of people have taken the Pfizer vaccine and within a couple of weeks one suspects that millions of people will have the astrazeneca vaccine in the UK and India. At present in the EU the option is Pfizer and the EU have purchased another few hundred million doses.they have millions of doses from moderna and I suspect moderna will get approval in EU soon. Reading the EMA site I would not be sure the Astrazeneca will be approved any time soon. however each country will get different quantities of differnt vaccines and others not mentioned on the blog have been approved in China, Russia, Middle East

    • Thank you very much for your reply. But I was wondering which of the two macro types of Vaccine (Pfizer / Moderna = RNA Vs Astrazeneca = viral vector) is the safest for those with multiple sclerosis and in my case taking Tysabri, given the side effects of Astrazeneca (1 of multiple sclerosis and two cases of transverse myelitis). thanks a lot

        • Thanks for the reply. Even here in Italy we cannot choose. I wonder if our healthcare facility does an analysis on which type of vaccine is best for me. thanks a lot

  • What would you use instead of amitriptyline if insomnia was also an issue as well as pain, and if the insomnia was menopause related would it work for for that?

  • Good post thanks Prof G and a wake up call for New Year!
    Neat calculator, crikey I’ve just scored 7! 😱 Something’s got to go, or at least be reduced…

    Bit of a blunt tool perhaps, the following all score 3 severe anticholinergic burden regardless of how much they cross blood brain barrier:
    Oxybutynin
    Fesoteradine
    Trospium
    Solifenacin
    Tolterodine
    Also no consideration of dose. Eg amitriptyline 10mg as taken by many pwMS versus 75mg to 150mg antidepressant dose. Big difference.

    Nevertheless, a useful reminder. Easy to accumulate polypharmacy. Did you know you can usually fit 4 items on an NHS FP10 (GP) prescription form? I aim this to be my maximum, more than one form is too much. I’m at my limit, another reason to ditch something.

    Good news, duloxetine burden minimal = nil points 🙂 duloxetine can stay!

  • Baclofen and tizanidine put me at 5! Ack. I don’t really know what I can do about that. Neither seems to have a replacement. I’ve been thinking of asking my neurologist to do Botox injections in my legs.
    She said that she would do it, but that she’d do one leg at a time. The way that she said it and idk, her expression, just made me think that she doesn’t have very much experience doing it. She’s the only neurologist at the MS clinic now. She’s about 37. There was a much older ms specialist at that ms center for a few years when she started, but he’s now retired.
    The first neurologist I had reserved one day every week for Botox lol. I only know that because he scheduled me for a semi emergency follow up and his nurse said “But that’s on Thursday, that’s Botox day.” Lol. He had her schedule me anyway, but said that he usually only did Botox injections on that day of the week. So he obviously did them a lot. He moved at the same time as I did in opposite directions, so I definitely couldn’t see him again darn it.
    I don’t really think that I have the option of asking that a different doctor who has more experience do it. What other types of doctors even do injections of Botox in legs to treat spasticity?

  • The only one I am on is cetirizine, and I was miserable when I went off of it for a week last year at the allergist’s request. I will try loratidine or fexofenadine instead, per the ACB link you shared. Thanks!

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