What is the recommended dose of modafinil (Provigil) for treating narcolepsy?

Modafinil Dosing for Narcolepsy

The recommended dose of modafinil for narcolepsy is 200 mg taken orally once daily in the morning, with the option to increase to 400 mg daily if needed, though doses above 200 mg do not consistently provide additional benefit. 1

Standard Dosing Regimen

• Start with 200 mg once daily in the morning as the FDA-approved initial and typical maintenance dose for narcolepsy 1
• Doses up to 400 mg/day as a single morning dose are well tolerated, but there is no consistent evidence that 400 mg provides additional benefit beyond 200 mg 1
• The maximum daily dose is 400 mg per day 2

Split-Dose Strategy for Late-Day Sleepiness

If patients experience residual late-afternoon or evening sleepiness despite adequate morning control, consider a split-dose regimen rather than simply increasing the total dose:

• 400 mg split dose (200 mg morning + 200 mg at noon) is significantly more effective than 200 mg once daily for sustaining wakefulness throughout the entire day 3, 4
• 600 mg split dose (400 mg morning + 200 mg at noon) may be superior to 400 mg once daily for late-day wakefulness, though this exceeds the FDA-approved maximum 5
• The split-dose approach specifically addresses the pharmacokinetic limitation of modafinil's 9-14 hour half-life, which may not provide adequate coverage for a full waking day 6
• 82% of patients on 400 mg once daily and 80% on 400 mg split dose were rated as "much improved" or "very much improved" for evening sleepiness, compared to only 27% on 200 mg once daily 3

Special Population Adjustments

Elderly patients require dose reduction:

• Start at 100 mg once upon awakening in the morning 7
• Increase at weekly intervals as necessary, with typical doses ranging from 200-400 mg per day 7
• Lower doses and close monitoring are recommended due to age-related pharmacokinetic changes 1

Severe hepatic impairment:

• Reduce dose to one-half of the normal recommended dose 1

Monitoring and Titration

• Increase doses at weekly intervals when titrating upward 7
• Monitor for common adverse effects including headache (most common), nausea, nervousness, insomnia, and dyspepsia 8, 2
• Assess for cardiovascular effects including hypertension, palpitations, and arrhythmias, particularly when initiating or adjusting doses 7
• Recognize that modafinil generally improves but does not eliminate sleepiness, requiring ongoing functional assessment 7

Critical Safety Considerations

Serious but rare risks require vigilance:

• Stevens-Johnson syndrome is a life-threatening risk—discontinue immediately at first sign of rash unless clearly not drug-related 8, 1
• Modafinil is not FDA-approved for patients under 17 years of age due to increased risk of serious rash (0.8% discontinuation rate in pediatric trials) 1
• It is a Schedule IV controlled substance with lower abuse potential than amphetamines but still carries risk of limited physical and psychological dependence 8, 2

Drug interactions and contraceptive considerations:

• Modafinil reduces effectiveness of oral contraceptives—use alternative or additional contraceptive methods during treatment and for one month after discontinuation 1
• May cause fetal harm based on animal data and reports of higher congenital anomalies—not recommended during pregnancy 8

Clinical Efficacy Evidence

• Modafinil significantly improves objective wakefulness on Multiple Sleep Latency Test and Maintenance of Wakefulness Test compared to placebo 9, 6
• Efficacy is maintained long-term (up to 40 weeks) without development of tolerance 9, 6
• Does not suppress cataplexy—separate treatment required for this symptom 6
• Does not cause rebound phenomena after treatment withdrawal, unlike amphetamines 6