What is the recommended treatment protocol for insomnia using Suvorexant (orexin receptor antagonist)?

Suvorexant Treatment Protocol for Insomnia

Start suvorexant at 10 mg taken once nightly within 30 minutes of bedtime (with at least 7 hours remaining before planned awakening), and increase to 20 mg if the 10 mg dose is well-tolerated but ineffective. 1

Primary Indication and Efficacy Profile

Suvorexant is FDA-approved for insomnia characterized by difficulties with sleep onset and/or sleep maintenance, though it demonstrates superior efficacy for sleep maintenance rather than sleep onset at lower doses. 2, 3

Key efficacy metrics:

• Reduces wake after sleep onset by 16-28 minutes at approved doses (≤20 mg) 3
• Improves total sleep time by approximately 10-22 minutes 3
• At 20 mg specifically, demonstrates clinically significant reduction in sleep latency, suggesting higher doses are needed for sleep onset problems 2, 3
• The American Academy of Sleep Medicine provides a weak recommendation for suvorexant as treatment for sleep maintenance insomnia, based on trials using 10,15/20, and 20 mg doses 2

Dosing Algorithm

Standard dosing approach:

1. Initial dose: 10 mg once nightly 1
2. Dose escalation: If 10 mg is well-tolerated but ineffective, increase to maximum 20 mg once nightly 1
3. Timing: Take within 30 minutes of bedtime with at least 7 hours remaining before planned awakening 1
4. Food interaction: Avoid taking with or soon after meals, as this delays time to effect 1

Special population adjustments:

• Obese women: Exercise particular caution before dose escalation due to increased exposure and higher risk of adverse effects 1
• Elderly patients (≥65 years): No dose adjustment required 4
• With moderate CYP3A inhibitors: Start at 5 mg, generally do not exceed 10 mg 1
• With strong CYP3A inhibitors: Not recommended 1
• With other CNS depressants: Consider dose reduction of suvorexant and/or the other CNS depressant 1

Safety Profile and Monitoring

Most common adverse effect:

• Somnolence occurs in approximately 7% of patients (versus 3% for placebo), with a number needed to harm of 13 for higher doses (40/30 mg) and 28 for lower doses (20/15 mg) 3, 5

Critical safety warnings:

• CNS depressant effects can impair daytime wakefulness even when used as prescribed 1
• Driving ability may be impaired; discontinue or decrease dose if daytime somnolence develops 1
• Impairment can occur in the absence of symptoms and may persist for several days after discontinuation 1
• FDA warns of potential cognitive and behavioral changes including amnesia, anxiety, hallucinations, and other neuropsychiatric symptoms 4
• Contraindicated in narcolepsy 1

Other adverse effects to monitor:

• Headache, dizziness, diarrhea, cough, abnormal dreams, upper respiratory tract infection 6
• Dry mouth 7

Advantages Over Traditional Hypnotics

Favorable withdrawal profile:

• No evidence of rebound insomnia or withdrawal effects after 3 months or 12 months of nightly use 5, 8
• This represents a significant advantage over benzodiazepines and Z-drugs 9

Long-term safety:

• Generally safe and well-tolerated over 1 year of nightly treatment 8
• Serious adverse events occurred in 5% of suvorexant-treated patients versus 7% of placebo patients in 1-year trials 8

Clinical Context and Treatment Positioning

Suvorexant should be considered a second-line treatment when cognitive behavioral therapy for insomnia (CBT-I) is unsuccessful, as CBT-I remains first-line treatment per the American College of Physicians. 4

Common pitfall to avoid: Do not use suvorexant as first-line therapy without attempting CBT-I first, unless there are compelling reasons to prioritize pharmacotherapy. 4