How can I manage insomnia in a patient who develops sleep difficulty after initiating atogepant for migraine prophylaxis?

Managing Insomnia in Patients Taking Atogepant for Migraine Prevention

First-Line Treatment: Cognitive Behavioral Therapy for Insomnia (CBT-I)

Initiate CBT-I immediately as the foundation of treatment, regardless of whether pharmacotherapy is added, because it provides superior long-term outcomes with sustained benefits after medication discontinuation. 1, 2

• CBT-I should include stimulus control therapy (going to bed only when sleepy, leaving bed after 20 minutes if unable to sleep, using bed only for sleep), sleep restriction therapy (limiting time in bed to match actual sleep time based on 2-week sleep log), relaxation techniques (progressive muscle relaxation, guided imagery), and cognitive restructuring of negative thoughts about sleep. 1, 2

• CBT-I can be delivered through individual therapy, group sessions, telephone-based programs, web-based modules, or self-help books—all formats show effectiveness. 1

Pharmacologic Options When CBT-I Alone Is Insufficient

For Sleep-Onset Insomnia

If insomnia persists after 2-4 weeks of CBT-I, add ramelteon 8 mg at bedtime as the first-line pharmacologic choice because it has no abuse potential, no DEA scheduling, minimal adverse effects, and no withdrawal symptoms. 1

• Alternative first-line options for sleep onset include zaleplon 10 mg (5 mg if ≥65 years) with its very short half-life providing rapid initiation with minimal next-day sedation, or zolpidem 10 mg (5 mg if ≥65 years) which reduces sleep-onset latency by approximately 25 minutes. 1

For Sleep-Maintenance Insomnia

Low-dose doxepin 3-6 mg at bedtime is the preferred first-line agent for sleep maintenance because it reduces wake after sleep onset by 22-23 minutes, has minimal anticholinergic effects at hypnotic doses, carries no abuse potential, and demonstrates moderate-quality evidence for efficacy. 1

• Suvorexant 10 mg is an alternative second-line option that reduces wake after sleep onset by 16-28 minutes through orexin-receptor antagonism, with lower risk of cognitive and psychomotor impairment than benzodiazepine-type agents. 1

For Combined Sleep-Onset and Maintenance Insomnia

Eszopiclone 2-3 mg at bedtime addresses both sleep initiation and maintenance with moderate-to-large improvement in sleep quality and 28-57 minutes increase in total sleep time. 1

Critical Safety Considerations

• All hypnotics should be prescribed at the lowest effective dose for the shortest necessary duration (typically ≤4 weeks for acute insomnia) because FDA labeling indicates these medications are intended for short-term use and long-term safety data beyond 4 weeks are limited. 1

• Reassess patients after 1-2 weeks to evaluate effects on sleep-onset latency, total sleep time, nocturnal awakenings, daytime functioning, and to monitor for adverse effects including morning sedation, cognitive impairment, complex sleep behaviors (sleep-driving, sleep-walking), falls, and fractures. 1

• Discontinue any hypnotic immediately if complex sleep behaviors occur and counsel patients to avoid alcohol while taking these medications. 1

Medications to Explicitly Avoid

• Do not use trazodone because it provides only approximately 10 minutes reduction in sleep latency and 8 minutes reduction in wake after sleep onset, with no improvement in subjective sleep quality, and adverse events occur in approximately 75% of older adults. 1

• Do not use over-the-counter antihistamines (diphenhydramine, doxylamine) because they lack efficacy data, cause strong anticholinergic effects (confusion, urinary retention, falls), and develop tolerance within 3-4 days. 1

• Do not use traditional benzodiazepines (lorazepam, clonazepam, diazepam) because they have long half-lives leading to drug accumulation, prolonged daytime sedation, increased fall and cognitive-impairment risk, and observational associations with dementia and fractures. 1

• Do not use antipsychotics (quetiapine, olanzapine) because they have weak evidence for insomnia benefit and significant risks including weight gain, metabolic dysregulation, extrapyramidal symptoms, and increased mortality in elderly patients. 1

Treatment Algorithm

1. Start CBT-I immediately for all patients with insomnia on atogepant, incorporating all core components (stimulus control, sleep restriction, relaxation, cognitive restructuring). 1, 2

2. If CBT-I alone is insufficient after 2-4 weeks, add first-line pharmacotherapy while continuing CBT-I:

   • Sleep-onset difficulty → ramelteon 8 mg, zaleplon 10 mg (5 mg if ≥65 years), or zolpidem 10 mg (5 mg if ≥65 years). 1
   • Sleep-maintenance difficulty → low-dose doxepin 3-6 mg or suvorexant 10 mg. 1
   • Combined difficulty → eszopiclone 2-3 mg. 1

3. If the first-line agent fails after 1-2 weeks, switch to an alternative agent within the same class rather than adding a second hypnotic. 1

4. Reassess every 2-4 weeks to evaluate efficacy, monitor for adverse effects, and plan tapering when conditions allow, using CBT-I to facilitate successful discontinuation. 1

Common Pitfalls to Avoid

• Failing to initiate CBT-I before or alongside pharmacotherapy is the most common error because behavioral interventions provide more durable benefits than medication alone. 1

• Using adult dosing in older adults (≥65 years) without age-adjusted reduction (e.g., zolpidem maximum 5 mg, eszopiclone maximum 2 mg) significantly increases fall risk and cognitive impairment. 1

• Combining multiple sedative agents markedly increases risk of respiratory depression, cognitive impairment, falls, and complex sleep behaviors. 1

• Continuing pharmacotherapy long-term without periodic reassessment (every 2-4 weeks initially, then every 4-6 weeks) to determine whether the hypnotic can be tapered as CBT-I effects consolidate. 1