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.