Anticholinergic drugs in subjects with Multiple Sclerosis (MS) and urinary symptoms.

Nicholas RS, Friede T, Hollis S, Young CA

Published Online:

January 21, 2009

Urinary symptoms are very common in people with multiple sclerosis, reflecting the high prevalence of damage to the spinal cord from MS. Symptoms may change with time due to either progression or MS relapses. Common symptoms include frequency, urgency and urinary incontinence.

Adults without neurological problems may experience urgency and incontinence, manifest as so called overactive bladder syndrome or an irritable bladder. While anticholinergic drugs may benefit individuals with overactive bladder syndrome due to their muscle relaxant action, in this review we did not find sufficient evidence to prove benefit from anticholinergic drugs in people with MS. This may reflect the lack of recent research on these medications in people with MS.

In the review we also noted a high rate of adverse effects with more than one in five trial participants having to withdraw from oral treatment. This may reflect a high risk of drug adverse effects in people with CNS damage from multiple sclerosis.

Abstract (click to read)

Background:

Multiple Sclerosis (MS) is the commonest physically disabling chronic neurological disease affecting young people. Urinary symptoms are present in about 68% of people with MS but their basis has a number of potential aetiologies that can change with time.

Objectives:

To assess the absolute and comparative efficacy, tolerability and safety of anticholinergic agents in MS patients.

Search strategy:

We searched the Cochrane Multiple Sclerosis Group Specialised Trials Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library 2008, Issue1), MEDLINE (January 1966 to January 2008), EMBASE (January 1974 to January 2008), supplemented with search of reference lists, personal communication with authors and relevant drug manufacturers.

Selection criteria:

Randomised trials and cross-over trials (blinded and unblinded) that are either placebo-controlled or comparing two or more treatments.

Data collection and analysis:

All four review authors independently assessed eligibility and trial quality, and extracted data. Data were processed as described in the Cochrane Handbook for Systematic Reviews of Interventions.

Main results:

Our search strategy identified 33 articles of which thirty were excluded. Three single centre trials were included. No details were given regarding randomisation and blinding in the first two trials but side effects were frequent with all treatments.

The first (Hebjorn 1977) was a double blind randomised crossover trial. Thirty four persons with MS received three drugs Methantheline Bromide, Flavoxate Chloride and Meladrazine Tartrate each for 14 days, washout periods were not mentioned. Median volume measurements at the first bladder contraction were statistically significant at a 5% level for Methantheline Bromide only compared to no treatment.

The second (Gajewski 1986) was a prospective parallel group randomised study. Thirty four persons with MS were treated for 6-8 weeks with Oxybutynin (19 subjects) or Propantheline (15 subjects). For frequency, nocturia, urgency, and urge incontinence differences in symptom grade in favour of Oxybutynin were found. However, only for frequency the difference was statistically significant at 5% level.

The third (Fader 2007) was a double blind crossover trial. Sixty four persons with MS received oral Oxybutynin or intravesical Atropine for 14 days. Details of randomisation and blinding were given. There was no significant difference between the two treatments in any efficacy outcome measure. Side effects and QOL scores showed significant differences in favour of atropine.

Authors' conclusions:

From the available evidence we cannot advocate the use of anticholinergics in MS.

This record should be cited as:

Nicholas RS, Friede T, Hollis S, Young CA. Anticholinergics for urinary symptoms in multiple sclerosis. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD004193. DOI: 10.1002/14651858.CD004193.pub2

Assessed as up to date:

January 30, 2008

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Primary Review Group:

Multiple Sclerosis and Rare Diseases of the Central Nervous System Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

How effective are anticholinergic agents for urinary symptoms in people with multiple sclerosis (MS)?

Bottom line:

In 1 trial, methantheline bromide, flavoxate chloride and meladrazine tartrate were compared to no treatment for 14 days each. Median volume measurements at the first bladder contraction were statistically significant at a 5% level for methantheline bromide only compared to no treatment. A prospective parallel group randomised study compared 6-8 weeks oxybutynin with propantheline. For frequency, nocturia, urgency and urge incontinence, differences in symptom grade in favour of oxybutynin were found. However, the difference was statistically significant at a 5% level for frequency only. A double-blind crossover trial comparing oral oxybutynin with intravesical atropine for 14 days showed no significant difference in any efficacy outcome measure. Side effects and quality of life scores showed significant differences in favour of atropine. The authors concluded that they could not advocate the use of anticholinergics in MS.

Caveat:

There was a high rate of adverse side effects, with more than 1 in 5 trial participants having to withdraw from oral treatment. This may reflect a high risk of drug adverse effects in people with CNS damage from MS.

Context:

MS is the commonest physically disabling chronic neurological disease affecting young people. Urinary symptoms (frequency, urgency and urinary incontinence) are present in about 68% of people with MS but their basis has a number of potential aetiologies that can change with time. Anticholinergics may benefit individuals with overactive bladder syndrome due to their muscle relaxant action, and have therefore been used in patients with MS.

Cochrane Systematic Review:

Nicholas RS et al. Anticholinergics for urinary symptoms in multiple sclerosis. Cochrane Reviews 2009, Issue 1. Article No. CD004193. DOI: 10.1002/14651858. CD004193.pub.2. This review contains 3 trials involving 132 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Health topics:

Neurology > Multiple sclerosis > Pharmacological treatments by clinical presentation

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Anticholinergic drugs in subjects with Multiple Sclerosis (MS) and urinary symptoms.

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