What is the appropriate dosing, titration, and safety considerations for using suvorexant in patients aged 65 years and older with insomnia?

Suvorexant Use in Elderly Patients

For elderly patients (≥65 years) with insomnia, use suvorexant 15 mg as the starting and maximum dose, taken nightly within 30 minutes of bedtime with at least 7 hours remaining before planned awakening. 1, 2

Dosing Recommendations

Standard Elderly Dosing

• Starting dose: 15 mg nightly for patients ≥65 years 1, 2
• Maximum dose: 15 mg (do not exceed this in elderly patients) 1, 2
• The 20 mg dose studied in younger adults is reduced to 15 mg in elderly populations due to age-adjusted dosing protocols 2, 3

Special Considerations for Obese Elderly Women

• Exercise particular caution in obese elderly females before considering any dose escalation 1
• Obese females show 46% higher AUC and 25% higher Cmax compared to non-obese females 1
• The average suvorexant concentration 9 hours post-dose is 15% higher in obese patients (BMI >30 kg/m²) 1
• In obese elderly women, maintain the 15 mg dose and do not increase 1

Administration Guidelines

• Take within 30 minutes of bedtime 1
• Ensure at least 7 hours available for sleep before planned awakening 1
• Avoid administration with food, as high-fat meals delay absorption by approximately 1.5 hours without improving efficacy 1
• Take on an empty stomach to maximize effectiveness 4

Efficacy in Elderly Patients

Sleep Maintenance (Primary Benefit)

• Suvorexant 15 mg demonstrates consistent efficacy for sleep maintenance across all time points in elderly patients 2
• Reduces wake after sleep onset by approximately 16-28 minutes at approved doses 5
• Improves polysomnographic and patient-reported sleep maintenance at Night 1/Week 1, Month 1, and Month 3 2, 3

Sleep Onset (Secondary Benefit)

• Sleep onset improvement is less robust at the 15 mg dose, particularly at later time points 2
• The 15 mg dose shows variable effects on latency to persistent sleep, with benefits diminishing over time 2
• For significant sleep onset effects, the 20 mg dose (used in younger adults) shows a clinically significant 22.3-minute reduction in sleep latency 4, 6

Duration of Effect

• Efficacy maintained over 3 months of nightly use 2, 3
• One trial included a 3-month extension demonstrating sustained benefit 7
• No evidence of tolerance development during treatment periods up to 12 months 8

Safety Profile in Elderly

Common Adverse Events

• Somnolence is the most frequent adverse event: 5.4% at 15 mg vs. 3.2% with placebo 2
• At the 30 mg dose (studied in some elderly patients): somnolence occurred in 8.8% vs. 3.2% placebo 2
• Overall discontinuation rate due to adverse events: 3.5% at 15 mg, 6.4% at 30 mg, vs. 5.5% placebo 2

Notable but Infrequent Side Effects

• Abnormal dreams (dose-related, generally mild) 9
• Sleep paralysis (dose-related, generally mild) 9
• Suicidal ideation (dose-related, generally mild) 9
• Potential for cataplexy or REM sleep behavior disorder given mechanism of action 9

Next-Day Effects

• Half-life of approximately 12 hours 1, 9
• At the approved 15 mg elderly dose, next-day sedation and driving impairment are much less apparent than at higher doses 9
• The FDA advises patients about possibility of next-day functional impairment, including driving 9
• Allow appropriate sleep time and avoid combining with alcohol or other sedatives 4

Withdrawal and Rebound

• No systematic evidence of rebound insomnia or withdrawal symptoms when discontinued after 3 months of nightly use 3, 7
• This contrasts with benzodiazepines, which can produce withdrawal symptoms with rapid dose decrease 4

Drug Interactions and Contraindications

Critical Drug Interactions

• Avoid combination with strong CYP3A inhibitors (suvorexant is metabolized primarily by CYP3A) 1, 9
• Minor contribution from CYP2C19 metabolism 1
• Additive effects with other CNS depressants and alcohol 4

Contraindications

• Contraindicated in narcolepsy 9
• Not recommended during pregnancy or nursing 4

Conditions Requiring Caution

• Signs/symptoms of depression 4
• Compromised respiratory function (asthma, COPD, sleep apnea) 4
• Hepatic or heart failure 4

Dose Adjustments Not Required

• No dose adjustment needed for advanced age alone 1
• No adjustment for renal impairment 1, 9
• No adjustment for mild-to-moderate hepatic impairment 1, 9
• Gender alone does not require adjustment (though females have 17% higher AUC) 1

Clinical Guideline Context

• The American Academy of Sleep Medicine suggests suvorexant primarily for sleep maintenance insomnia with a weak recommendation 5, 10
• The AASM judged overall benefits outweigh potential harms based on clinical trial data 4
• Suvorexant represents the first orexin receptor antagonist approved for insomnia, offering a novel mechanism distinct from benzodiazepine receptor agonists 9

Common Pitfalls to Avoid

• Do not use the 20 mg dose in elderly patients—the age-adjusted dose is 15 mg 2, 3
• Do not administer with food—this delays absorption without benefit 1
• Do not combine with strong CYP3A inhibitors—this significantly increases drug levels 1, 9
• Do not expect robust sleep onset effects at 15 mg—this dose primarily benefits sleep maintenance 2
• Do not escalate dose in obese elderly women—they already have substantially higher drug exposure 1