Thursday, 28 January 2016

ClinicSpeak & BrainHealth: solifenacin trial shows positive influence on bladder function

Are you on a centrally acting anticholinergic? If yes, you may want to consider stopping it. #ClinicSpeak #BrainHealth #MSBlog #MSResearch

"The study below shows that the drug solifenacin (Vesicare), a so called anti-cholinergic drug of the antimuscarinic class, is effective in reducing contractions of overactive bladders and increasing bladder volume. This results in reduced urinary frequency, urgency, urge incontinence and nocturia (need to pass urine at night). These findings are not new; we have been using solifenacin for years and a large number of pwMS find it helpful."

"What is not covered in this abstract is the real reason why solifenacin (Vesicare) is so much better than oxybutynin (Ditropan) and older generation anticholinergic drug. Oxybutynin crosses the blood brain barrier and enters the brain and blocks brain cholinergic receptors, which impairs cognition. Studies suggest that centrally  acting anticholinergics, such as oxybutynin,  clips IQ by about 7 IQ points or half a standard deviation. This effect is not trivial given that the majority of people with established MS, and bladder problems, already have cognitive problems. In comparison solifenacin, and the other newer generation anticholinergics, don't cross into the brain to the same extent and therefore have a minimal impact on cognition. Why take a drug that impairs cognition when you can take an alternative that does not?"


"Are there any other anticholinergic drugs that affect cognition that you should be aware of? Yes, tricyclic antidepressants, for example amitriptyline, and older generation antihistamines also have central anticholinergic effects and affect cognition. It has recently been shown that long term exposure to anticholinergics is a risk factor for dementia in later life. Therefore one component of our Brain Health initiative is try and get pwMS to avoid or stop centrally acting anticholinergic drugs and other drugs that affect cognition."

"If you are on one of the drugs that has centrally acting anticholinergic effects I suggest you discuss the possibility of stopping the medication, or switching to alternative medication, with your neurologist or family doctor."

Epub: Amarenco et al. Solifenacin is effective and well tolerated in patients with neurogenic detrusor overactivity: Results from the double-blind, randomized, active- and placebo-controlled SONIC urodynamic study. Neurourol Urodyn. 2015 . doi: 10.1002/nau.22945.

AIMS: To investigate the effect on urodynamics of 4 weeks treatment with solifenacin succinate in patients with neurogenic detrusor overactivity (NDO) due to multiple sclerosis (MS) or spinal cord injury (SCI).

METHODS: SONIC was a prospective, multicenter, double-blind, phase 3b/4 study investigating the efficacy and safety of solifenacin 10 mg in patients with NDO due to MS or SCI. Patients (n = 189) were randomized to placebo or active treatment (solifenacin 5 mg, 10 mg or oxybutynin hydrochloride 15 mg) for 4 weeks, after a 2-week, single-blind, placebo run-in period. The primary endpoint was change in maximum cystometric capacity (MCC) from baseline to end of treatment. The primary analysis compared solifenacin 10 mg versus placebo; all other comparisons were considered secondary. Secondary endpoints included changes in urodynamic parameters, patient-reported outcomes, and safety assessments.

RESULTS: In the primary analysis, solifenacin 10 mg significantly improved mean change from baseline MCC versus placebo (P < 0.001) and was associated with improvements in bladder volume at first contraction and at first leak as well as detrusor pressure at first leak. Similar results were obtained for oxybutynin versus placebo. Patient perception of bladder condition significantly improved with solifenacin 10 mg versus placebo (P = 0.041). There was a clear improvement in quality of life (QoL) in the solifenacin arms versus placebo. The overall incidence of adverse events was low.

CONCLUSIONS: In patients with NDO due to MS and SCI, 4 weeks of treatment with solifenacin 10 mg improved urodynamic variables and QoL versus placebo and was well tolerated

CoI: multiple

14 comments:

  1. I've done a search on anticholinergic drugs and they have a wide range of uses. The following website page says

    Anticholinergic drugs are used to treat a variety of conditions:

    Gastrointestinal disorders (e.g., gastritis, diarrhea, pylorospasm, diverticulitis, ulcerative colitis, nausea, and vomiting)

    Genitourinary disorders (e.g., cystitis, urethritis, and prostatitis)

    Respiratory disorders (e.g., asthma, chronic bronchitis, and chronic obstructive pulmonary disease [COPD])

    Sinus bradycardia due to a hypersensitive vagus nerve.

    Insomnia, although usually only on a short-term basis.

    Dizziness (including vertigo [a.k.a. 'the spins'] and motion sickness-related symptoms)

    https://en.wikipedia.org/wiki/Anticholinergic

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    1. Re: "anticholinergic drugs and they have a wide range of uses"

      Yes, that is correct. Please note that most 'new generation' anticholinergics are designed not to cross the blood-brain-barrier and hence have no impact on cognition. In addition, the short-term use of centrally acting anticholinergics is unlikely to be a problem. The long-term use is much more of a problem.

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    2. Thanks Prof G. It's something to think about with the medications MSers take including for gastro problems when taking Tecfidera. Though hopefully the gastro problems are short term.
      Insomnia and dizziness.

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  2. Thanks for the article - could I just confirm my understanding? Solefenicin is not a centrally acting anti-cholinergic and largely ok, as "a so called anti-cholinergic drug of the antimuscarinic class" - it's a modern version so not as likely to be linked with dementia as amitriptyline?

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  3. Before I worked out what was irritating my bladder (mainly salt and caffeine), I was offered some sort of overactive bladder drug. Partly through the information within a previous post on this blog about possible cognitive implications, I gave that a body swerve. I can't thank you enough, particularly since things settled without medication anyway.

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  4. Some anti-muscarinic agents were proposed to promote (re)myelination Are there any new data on this?

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  5. Has published studies in 2014 and 2015 claiming that Solifenacin seems to promote remyelination, promotes the if I'm not mistaken the OPCs. I think including MD talked about it here on the blog ...

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  6. Thanks ProfG for the post I did not know that. Will swap oxybutynin to newer anticholinergic ASAP.

    On similar topic my GP advised against even short term benzodiazepine treatment due to dementia risk.

    Do we know yet about long term treatment with other classes of centrally acting drugs in MS? I read here that baclofen as GABA b agonist probably neuroprotective? Gabapentin and Pregabalin pharmacology a bit more complicated any risk known yet with these relatively new drugs? I do worry about any drug with a full bnf page devoted to warnings about side effects and stopping treatment!

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  7. Is the amitriptyline dementia connection linked to the dosage or the number of years taken or both?

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    1. Re: "Is the amitriptyline dementia connection linked to the dosage or the number of years taken or both?"

      The risk only increases after at least a year of exposure of at least 10mg of Amitriptyline per day; at this level of exposure, or greater, increased your risk by ~54% (95%CI 21%-96%). I have posted on this topic before so it should be new to you; please post below.

      http://multiple-sclerosis-research.blogspot.com/2015/04/clinicspeak-anticholinergics-increase.html

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  8. Please note that solifenacin is only relatively safer than oxybutynin; no drug is 100% excluded from the central nervous system.

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    1. Particularly since many pwMs have a leakier blood/brain barrier thean healthy people as a result of their MS.

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  9. I take mirabegron (Betmiga), a newer antimuscarinic, and it's been very much more effective for me than solinefacin was.

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  10. Thanks for review. Solifenacin, as you state Dr. G, cannot cross the BBB as freely as Oxybutnin and therefore causes less anticholinergic effects on the brain receptors thereby causing less decline in cognition. If this is the case, then Solifenacin, as a remyelinating agent, is theoretically troublesome as it would have to be given intrathecally to have any significant effect. Recent studies by University of Buffalo, have successfully shown in animal models that Solifenacin successfully remyelinates neurons by mobilizing oligodendrocyte progenitors that are "stuck".

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