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

Suvorexant Treatment Protocol for Insomnia

Suvorexant is recommended primarily for sleep maintenance insomnia at a starting dose of 10 mg taken once nightly within 30 minutes of bedtime, with at least 7 hours remaining before planned awakening, and can be increased to a maximum of 20 mg if the lower dose is well-tolerated but ineffective. 1

Dosing Protocol

Standard Dosing

• Initial dose: 10 mg once nightly 1
• Take within 30 minutes of going to bed 1
• Ensure at least 7 hours remain before planned awakening 1
• If 10 mg is well-tolerated but ineffective, increase to 20 mg (maximum dose) 1
• Take on an empty stomach or avoid taking with/soon after meals, as food delays time to effect 1

Special Populations

• Obese women: Exercise particular caution before dose escalation due to increased drug exposure and higher risk of adverse effects 1
• Elderly patients (≥65 years): The 15 mg dose was effective in clinical trials, though 10 mg remains the standard starting dose 2, 3
• With moderate CYP3A inhibitors: Reduce dose to 5 mg (generally should not exceed 10 mg) 1
• With strong CYP3A inhibitors: Suvorexant is not recommended 1

Combination with CNS Depressants

• Reduce suvorexant dose and/or the other CNS depressant when used together due to additive effects 1

Clinical Efficacy Profile

Sleep Maintenance (Primary Indication)

The American Academy of Sleep Medicine suggests suvorexant primarily for sleep maintenance insomnia with a weak recommendation 2, 4. The evidence shows:

• Wake after sleep onset: Reduces by 16-28 minutes at approved doses (≤20 mg) 4
• Total sleep time: Improves by 10-22 minutes at pooled 15/20 mg doses 2, 4
• Sleep efficiency: Demonstrates clinically significant improvements at 10 mg 5

Sleep Onset (Secondary Benefit)

• At 10 mg: Minimal improvement in sleep latency (2.3 min reduction), not clinically significant 2
• At 20 mg: Clinically significant reduction in sleep latency of 22.3 minutes 2, 4
• Higher doses provide additional benefits for sleep onset, though the drug shows greater efficacy for sleep maintenance at lower doses 4, 5

Treatment Duration and Long-Term Use

• Suvorexant demonstrated sustained efficacy over 3 months in phase 3 trials 6, 3
• One-year safety and efficacy data show continued benefit with good tolerability 7
• At 1 month, suvorexant improved subjective total sleep time by 38.7 minutes versus 16.0 minutes for placebo (difference 22.7 minutes) 7
• No systematic evidence of rebound insomnia or withdrawal symptoms after 3 months of nightly use 6
• Abrupt discontinuation after 1 year showed no significant withdrawal effects 7

Safety Profile and Adverse Effects

Common Adverse Events

• Somnolence: Most common adverse effect, occurring in approximately 7% of patients (versus 3% for placebo) 4
• In 3-month trials: 6.7% experienced somnolence with 20/15 mg dose versus 3.3% with placebo 6
• In elderly patients: 8.8% with 30 mg, 5.4% with 15 mg, 3.2% with placebo 3
• Other common effects: headache, dizziness, diarrhea, cough, abnormal dreams, upper respiratory tract infection 8, 9

Discontinuation Rates

• 3% discontinued due to adverse events over 3 months with 20/15 mg dose versus 5.2% with placebo 6
• In elderly: 6.4% discontinued with 30 mg, 3.5% with 15 mg, 5.5% with placebo over 3 months 3

Important Safety Warnings

• CNS depression and daytime impairment: Can impair daytime wakefulness even when used as prescribed 1
• Impairment may persist for several days after discontinuation 1
• Driving impairment: Discontinue or decrease dose if daytime somnolence develops in patients who drive 1
• At 20 mg, driving ability was impaired in some healthy adults 1
• Monitor for somnolence, though impairment can occur without obvious symptoms 1

Contraindications

• Absolute contraindication: Narcolepsy 1

Clinical Context and Treatment Algorithm

Position in Treatment Hierarchy

According to the 2008 American Academy of Sleep Medicine guidelines, the general approach to insomnia treatment should follow this sequence 2:

1. First-line: Behavioral interventions (CBT-I, stimulus control, relaxation therapy)
2. Pharmacologic options when behavioral therapy is insufficient or combined with behavioral therapy:
   • Short-intermediate acting benzodiazepine receptor agonists (BZDs, BzRAs) or ramelteon
   • Alternate BzRAs if initial agent unsuccessful
   • Sedating antidepressants (especially with comorbid depression/anxiety)
   • Combined therapy

The 2017 American Academy of Sleep Medicine guideline provides a weak recommendation for suvorexant specifically for sleep maintenance insomnia 2, placing it among other recommended agents including doxepin, eszopiclone, temazepam, and zolpidem 2.

Key Clinical Pitfalls to Avoid

• Do not use with strong CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) 1
• Avoid taking with or immediately after meals as this delays onset of effect 1
• Do not take unless 7+ hours available for sleep to minimize next-day impairment 1
• Be cautious in obese women before escalating dose due to increased exposure 1
• Monitor driving ability and discontinue if daytime somnolence develops 1

When to Choose Suvorexant Over Other Hypnotics

Suvorexant is particularly appropriate when:

• Sleep maintenance is the primary complaint (more so than sleep onset at lower doses) 2, 4, 5
• Concerns exist about dependence potential with benzodiazepines
• Patient requires long-term treatment (demonstrated safety up to 1 year) 7
• Minimal withdrawal/rebound effects are desired 6, 7