What is the appropriate use and dosage of Modafinil (a prescription medication) for treating sleep disorders, such as narcolepsy, shift work sleep disorder, and obstructive sleep apnea, in adults, and attention deficit hyperactivity disorder (ADHD) in children and adolescents?

Modafinil: Clinical Use and Dosing

Primary Indications and First-Line Recommendations

Modafinil 200 mg once daily in the morning is the recommended first-line treatment for excessive daytime sleepiness in adults with narcolepsy, obstructive sleep apnea (as adjunct to CPAP), shift work sleep disorder, and idiopathic hypersomnia. 1, 2

FDA-Approved Indications

• Narcolepsy: 200 mg orally once daily in the morning 2
• Obstructive Sleep Apnea (OSA): 200 mg orally once daily in the morning, only as adjunct to CPAP therapy, not as treatment for underlying airway obstruction 2
• Shift Work Sleep Disorder (SWD): 200 mg orally once daily, taken approximately 1 hour before work shift starts 2

Guideline-Supported Uses

The American Academy of Sleep Medicine provides STRONG recommendations for modafinil in:

• Idiopathic hypersomnia in adults 1

The American Academy of Sleep Medicine provides CONDITIONAL recommendations (weaker evidence but still supported) for modafinil in:

• Hypersomnia secondary to Parkinson's disease 1
• Hypersomnia secondary to traumatic brain injury 1
• Hypersomnia secondary to myotonic dystrophy 1

Dosing Algorithm

Standard Adult Dosing

1. Start: 200 mg once daily in the morning 2
2. Maximum: 400 mg once daily if needed, though no consistent evidence shows additional benefit beyond 200 mg/day 2
3. Timing: Single morning dose for narcolepsy/OSA; 1 hour before shift for SWSD 2

Special Population Adjustments

Severe hepatic impairment: Reduce dose to 100 mg once daily (half the standard dose) 2

Elderly patients: Consider starting with lower doses (100 mg) and monitor closely due to potential for decreased hepatic/renal clearance 2

Severe renal insufficiency: Use caution due to substantial increases in modafinil acid metabolite levels 3

Critical Safety Warnings

Serious Dermatologic Reactions (Black Box Concern)

Modafinil is NOT approved for pediatric use due to serious skin reactions, including Stevens-Johnson Syndrome, occurring in approximately 0.8% of pediatric patients in clinical trials. 2, 4

• Rare cases of Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and DRESS syndrome reported in adults and children 2
• Discontinue immediately at first sign of rash unless clearly not drug-related 2

Pregnancy and Contraception

Modafinil may cause fetal harm based on animal data, with a 2018 registry report showing higher rates of major congenital anomalies in children exposed in utero. 1, 4, 2

• Modafinil reduces effectiveness of oral contraceptives 1, 4, 2
• Use alternative or additional contraceptive methods during treatment and for 1 month after discontinuation 2

Controlled Substance Status

Modafinil is a Schedule IV controlled substance with potential for abuse or dependency, though abuse potential is lower than amphetamines 1, 4, 3

Common and Serious Adverse Effects

Most Common (≥5% incidence)

• Headache (34% vs 23% placebo) 5, 4
• Insomnia 1, 4
• Nausea (11% vs 3% placebo) 5, 4
• Diarrhea 1, 4
• Dry mouth 1, 4
• Nervousness, anxiety 2
• Dizziness, dyspepsia 2

Cardiovascular Monitoring Required

Monitor blood pressure and heart rate regularly, particularly at treatment initiation and dose adjustments. 4

• Clinically significant increases in diastolic/systolic blood pressure occur infrequently (<1% of patients) 5
• Palpitations and arrhythmias possible 4
• Consider increased monitoring in patients with known cardiovascular disease 2

Clinical Efficacy Evidence

Narcolepsy

Nine randomized controlled trials and 4 observational studies demonstrated clinically significant improvements in excessive daytime sleepiness, disease severity, and quality of life with moderate-quality evidence 1

Obstructive Sleep Apnea

Critical caveat: Modafinil treats residual excessive sleepiness despite optimal CPAP use; maximal effort to treat with CPAP must be made before and during modafinil therapy 2

Shift Work Sleep Disorder

Significant improvements on Multiple Sleep Latency Test, Maintenance of Wakefulness Test, and Clinical Global Impression of Change 6

Drug Interactions

Modafinil induces and inhibits multiple cytochrome P450 isoenzymes, creating interaction potential across all drug classes. 3

Key Interactions

• Oral contraceptives: Reduced effectiveness (use backup contraception) 1, 2
• Cyclosporine: Blood concentrations may be reduced 2
• CYP2C19 substrates (omeprazole, phenytoin, diazepam): Increased exposure 2

Monitoring Protocol

Schedule more frequent follow-up visits when starting or adjusting modafinil doses. 4, 7

Monitor for:

• Blood pressure and heart rate elevation 4
• Palpitations, arrhythmias 4
• Skin reactions (especially in first weeks) 2
• Psychiatric symptoms (irritability, depression, anxiety) 4
• Persistent sleepiness despite treatment 2

Not Recommended For

ADHD in children and adolescents: Despite efficacy in trials, modafinil is not FDA-approved due to serious dermatological toxicity risk 3

Cataplexy: Modafinil does not benefit cataplexy symptoms in narcolepsy 3

Pregnancy: Avoid due to fetal harm risk unless benefits clearly outweigh risks 1, 4, 2