What is the recommended treatment for a 61-year-old woman with multiple sclerosis (MS) and excessive daytime sleepiness (EDS) despite adequate nighttime sleep, with no sleep-disordered breathing?

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Recommended Treatment for MS-Related Excessive Daytime Sleepiness

Start modafinil 100 mg once upon awakening in the morning for this 61-year-old woman with multiple sclerosis and excessive daytime sleepiness. 1, 2

Rationale for Modafinil as First-Line

Modafinil is the evidence-based first-line pharmacologic treatment for excessive daytime sleepiness in older adults with central hypersomnolence disorders. 3, 1, 2 The American Geriatrics Society specifically recommends starting modafinil at 100 mg once upon awakening in elderly patients, with dose increases at weekly intervals as necessary, typically ranging 200-400 mg daily. 1, 2

Key advantages of modafinil include:

  • Safer side-effect profile compared to traditional sympathomimetic stimulants like methylphenidate and amphetamines 4
  • Established efficacy for central hypersomnolence disorders including narcolepsy and idiopathic hypersomnia 2, 5
  • Lower risk of cardiovascular adverse effects, behavioral disturbances, and dependency compared to traditional stimulants 4, 6

Why Not the Other Options

Solriamfetol (option d) is primarily indicated for residual excessive daytime sleepiness in obstructive sleep apnea despite adequate CPAP therapy, or as an alternative when patients refuse/are intolerant to conventional OSA therapy. 7 This patient has no sleep-disordered breathing, making solriamfetol less appropriate as first-line therapy. Additionally, solriamfetol requires strict monitoring for cardiovascular events and has higher cardiovascular risk compared to modafinil. 7

Methylphenidate (option c) is considered a second-line agent, reserved for patients who fail to respond adequately to modafinil. 1, 5, 6 The National Comprehensive Cancer Network suggests methylphenidate starting at 2.5-5 mg orally with breakfast, but only after considering modafinil first. 1 Furthermore, methylphenidate carries higher risks of hypertension, palpitations, arrhythmias, irritability, and behavioral manifestations requiring more intensive monitoring. 3, 1

Bupropion (option a) lacks systematic evidence for treating excessive daytime sleepiness in central hypersomnolence disorders and is not recommended in guidelines for this indication. 3

Clinical Implementation Algorithm

Initial dosing:

  • Start modafinil 100 mg once upon awakening 1, 2
  • Establish baseline blood pressure before initiating therapy 1

Dose titration:

  • Increase at weekly intervals as necessary based on response 1, 2
  • Typical therapeutic range: 200-400 mg daily 1, 2

Monitoring requirements:

  • More frequent follow-up when starting or adjusting doses 3, 2
  • Monitor for hypertension, palpitations, arrhythmias, irritability, or behavioral changes 3, 1
  • Use Epworth Sleepiness Scale at each visit to track treatment response 3, 1, 2
  • Assess functional status and daytime alertness 1

Important Caveats

This is likely a long-term condition requiring ongoing management. 3, 2 Multiple sclerosis-related fatigue and sleepiness often represent chronic symptoms that necessitate sustained pharmacologic therapy.

Modafinil generally improves but does not eliminate sleepiness. 3 Frequent reassessment of functional impairments due to residual sleepiness remains necessary throughout treatment.

Consider sleep specialist referral if the patient remains unresponsive to initial modafinil therapy or if symptoms worsen despite treatment optimization. 3, 2

References

Guideline

Managing Excessive Somnolence in Patients with Alzheimer's Disease

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Narcolepsy Management Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pharmacotherapy for excessive daytime sleepiness.

Sleep medicine reviews, 2004

Research

Treatment of Excessive Daytime Sleepiness in Patients with Narcolepsy.

Current treatment options in neurology, 2019

Research

Excessive Daytime Sleepiness: A Clinical Review.

Mayo Clinic proceedings, 2021

Research

[Expert consensus on the diagnosis and treatment of excessive daytime sleepiness in obstructive sleep apnea].

Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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