How to manage insomnia in a patient with Multiple Sclerosis (MS)?

Managing Insomnia in Multiple Sclerosis Patients

Start with Cognitive Behavioral Therapy for Insomnia (CBT-I) as first-line treatment, which has demonstrated significant efficacy specifically in MS patients with high retention rates and improvements in insomnia severity, sleep quality, fatigue, and depression. 1, 2

Initial Treatment Approach: CBT-I

CBT-I should be implemented immediately as the foundation of treatment for any MS patient presenting with insomnia, as it addresses both sleep disturbance and the multifactorial contributors unique to MS. 3, 1

Core CBT-I Components for MS Patients:

• Stimulus control therapy: Go to bed only when sleepy, maintain regular schedule, avoid naps, use bed only for sleep, and leave bed after approximately 20 minutes if unable to sleep—engage in relaxing activity until drowsy then return. 3

• Sleep restriction therapy: Track total sleep time via sleep log for 1-2 weeks, then limit time in bed to match actual sleep time (minimum 5 hours) to achieve >85% sleep efficiency, adjusting by 15-20 minutes weekly based on sleep efficiency calculations. 3

• Cognitive therapy: Address distorted beliefs about sleep including "I can't sleep without medication," "If I can't sleep I should stay in bed and rest," and "My life will be ruined if I can't sleep." 3

• Relaxation training: Progressive muscle relaxation involving methodical tensing and relaxing of different muscle groups throughout the body. 3

Evidence Specific to MS Population:

MS patients completing CBT-I demonstrate 100% retention and adherence rates with significant improvements in insomnia severity, sleep quality, fatigue severity, sleep onset latency, sleep self-efficacy, depression, and MS-specific quality of life. 1, 2 Telehealth-delivered CBT-I produces equivalent outcomes to in-person treatment, making it particularly valuable for MS patients with mobility limitations or fatigue. 1

Pharmacological Treatment Algorithm

If CBT-I alone is insufficient after 2-4 weeks, add pharmacological therapy while continuing CBT-I. 3, 4, 5

First-Line Pharmacological Options:

• Short-intermediate acting benzodiazepine receptor agonists (BzRAs): Zolpidem (5-10mg), eszopiclone, zaleplon, or temazepam as initial agents. 3, 6

  • Zaleplon and ramelteon have very short half-lives, reducing sleep latency with minimal effect on sleep maintenance and unlikely to cause residual sedation. 3
  • Eszopiclone and temazepam have longer half-lives, improving sleep maintenance but with higher risk of residual sedation. 3
  • Zolpidem 10mg is superior to placebo on sleep latency and efficiency for up to 4 weeks in chronic insomnia. 6

• Ramelteon: Appropriate for patients preferring non-DEA-scheduled drugs or those with substance use history, particularly effective for sleep initiation difficulty. 3

Second-Line Pharmacological Options:

If initial BzRA or ramelteon is unsuccessful, switch to alternative agent within same class based on symptom pattern: patients with continued sleep maintenance problems need longer half-life agents; those with residual sedation need shorter-acting drugs. 3

If BzRAs fail or are contraindicated, use sedating antidepressants: 3, 4

• Trazodone 25-50mg (preferred option). 4, 5
• Doxepin 3-6mg. 4, 5
• Amitriptyline or mirtazapine (particularly if comorbid depression/anxiety). 3

Third-Line Options:

For severe refractory cases, consider: 3

• Combined BzRA/ramelteon with sedating antidepressant. 3
• Gabapentin (doses around 1300mg), which has shown moderate to marked improvement in insomnia particularly when significant somatic symptoms present. 5
• Anti-epilepsy medications (tiagabine) or atypical antipsychotics (quetiapine, olanzapine) only when comorbid conditions warrant their primary action. 3

MS-Specific Considerations

Address MS-related factors that disrupt sleep: 7, 8, 9

• Pain management: Pain is significantly associated with poor sleep quality in MS patients with longer disease duration (>5 years). 9
• Nocturia: Bladder dysfunction is a common MS symptom disrupting sleep continuity. 7, 9
• Depression and anxiety: Anxiety and reduced motivation associate with poor sleep in early MS (≤5 years), while depression and mental fatigue predominate in longer disease duration. 9
• Medication effects: Review disease-modifying therapies and symptomatic treatments that may impact sleep. 7

Critical Pitfalls to Avoid

Do not use over-the-counter antihistamines or herbal supplements (valerian, melatonin) due to lack of efficacy and safety data in chronic insomnia. 3, 4

Avoid barbiturates, barbiturate-type drugs, and chloral hydrate as they are not recommended for insomnia treatment. 3

Do not prescribe benzodiazepines not specifically approved for insomnia (lorazepam, clonazepam) as first-line agents, though they may be considered in refractory cases. 3

Monitoring and Follow-Up

Reassess every few weeks initially to evaluate effectiveness, side effects, and need for ongoing medication. 3, 4

Provide patient education regarding: treatment goals and expectations, safety concerns, potential side effects and drug interactions, cognitive-behavioral treatment options, potential for dosage escalation, and rebound insomnia. 3

Attempt medication tapering when conditions allow, facilitated by concurrent CBT-I, using lowest effective maintenance dosage. 3

Long-term hypnotic use may be indicated for severe or refractory insomnia in MS, administered nightly, intermittently (three nights per week), or as needed, with consistent follow-up and monitoring for adverse effects. 3