Management of Urinary Symptoms in Multiple Sclerosis

Pharmacological Approach

• The European Association of Urology recommends a combination of alpha-1 adrenoceptor antagonists plus antimuscarinic or beta-3 agonist therapy as the most effective pharmacological approach for males with Multiple Sclerosis experiencing both urinary urgency and retention 1
• Combination therapy has shown superior efficacy compared to monotherapy for patients with mixed storage and voiding symptoms 1
• Mirabegron (beta-3 adrenergic agonist) is the preferred pharmacological option for elderly patients with OAB, due to its better side effect profile, particularly regarding cognitive effects, while maintaining similar efficacy for symptom control, as recommended by the American Urological Association and supported by the European Association of Urology 2, 3, 4

Treatment Considerations

• The European Association of Urology guidelines suggest measuring post-void residual (PVR) volume before initiating antimuscarinic therapy, and not using antimuscarinic medications if PVR is high due to risk of urinary retention 1, 3
• Implement pelvic floor muscle training to improve bladder control, as recommended by the American Urological Association 5
• Institute bladder training with delayed voiding to increase bladder capacity, as suggested by the American Urological Association 5
• Avoid bladder irritants, such as caffeine, alcohol, and spicy foods, to reduce symptoms, as advised by the American Urological Association 6
• Recommend fluid management, such as a 25% reduction in fluid intake, to reduce frequency and urgency, as reported by the American Urological Association 5
• Suggest weight loss, with an 8% weight reduction in obese women, to reduce incontinence episodes by 42-47%, as found by the American College of Physicians and the American Urological Association 5, 4
• Consider peripheral tibial nerve stimulation (PTNS) for patients who do not respond to initial treatments, as recommended by the American Urological Association 5
• Intradetrusor onabotulinumtoxinA injections may be considered, but with caution due to the risk of urinary retention, and only if the patient is willing and able to perform self-catheterization, as suggested by the American Urological Association 5
• Sacral neuromodulation may be considered in select cases, as recommended by the American Urological Association 5

Medication Selection and Management

• Trospium chloride is a good option for elderly patients due to reduced blood-brain barrier penetration, with moderate quality evidence showing a number needed to harm (NNH) of 8 for adverse effects, as recommended by the American College of Physicians 4
• Fesoterodine has more adverse effects than tolterodine, with a NNH of 11, and a higher discontinuation rate due to adverse effects compared to tolterodine, as reported by the American College of Physicians 4
• Darifenacin has similar discontinuation rates to placebo, and less cognitive effects than other antimuscarinic agents, as noted by the American College of Physicians 4
• Oxybutynin has the highest risk for discontinuation due to adverse effects among all antimuscarinic agents, with a higher risk of cognitive impairment, particularly in elderly patients, as warned by the American College of Physicians 4
• The American Urological Association recommends mirabegron plus solifenacin 5mg for patients with inadequate response to monotherapy, with improved efficacy shown in the SYNERGY and BESIDE trials, and a side effect profile similar to monotherapy 7
• The following table summarizes the contraindications and adverse events of mirabegron:

Monitoring and Follow-up

• Assess treatment response after 4-8 weeks to determine efficacy, as recommended by the American Urological Association 5
• Assess post-void residual if symptoms worsen to evaluate bladder function, as suggested by the American Urological Association 6
• Annual follow-up is recommended to reassess symptoms and treatment efficacy, as advised by the American Urological Association 6
• Consider periodic cognitive assessments in long-term users of anticholinergics, and monitor blood pressure regularly in patients taking mirabegron, as noted by the American Academy of Neurology and the American Heart Association 3
• Regular blood pressure monitoring is essential, especially in patients with pre-existing hypertension, as recommended by the American Heart Association and the National Institute for Health and Care Excellence 4, 1
• Monitoring for urinary retention and constipation is also necessary, as advised by the National Institute for Health and Care Excellence and the American Urological Association 1, 7

Dosing and Administration

• The recommended starting dose of mirabegron is 25 mg once daily, with potential increase to 50 mg once daily if needed and tolerated, as advised by the National Institute on Aging and supported by the AUA/SUFU guidelines 4, 7
• No dose adjustment is necessary based on age alone, according to the American College of Clinical Pharmacology 4
• For patients with severe renal impairment (eGFR 15-29 mL/min/1.73 m²), the daily dose of mirabegron should not exceed 25 mg, as recommended by the National Kidney Foundation 4
• Mirabegron should be taken with food in elderly patients to reduce potential exposure-related risks, as advised by the Gerontological Society of America 4