Modafinil: Clinical Use Guide
Primary Indications
Modafinil is FDA-approved for excessive daytime sleepiness in narcolepsy, obstructive sleep apnea (OSA), and shift work disorder (SWD), with the American Academy of Sleep Medicine providing STRONG recommendations for its use in narcolepsy and idiopathic hypersomnia. 1, 2
Evidence-Based Indications by Strength:
STRONG recommendations:
CONDITIONAL recommendations:
- Hypersomnia secondary to Parkinson's disease 2
- Hypersomnia secondary to traumatic brain injury 2
- Hypersomnia secondary to myotonic dystrophy 2
Important limitation: In OSA, modafinil treats only excessive sleepiness and is NOT a treatment for the underlying airway obstruction—patients must continue CPAP therapy. 1
Dosing
Standard Dosing:
- Narcolepsy or OSA: 200 mg once daily in the morning 1
- Shift work disorder: 200 mg once daily, taken approximately 1 hour before the work shift 1
- Maximum daily dose: 400 mg per day 3, 1
Dosing Strategy by Clinical Goal:
- For sleepiness: Use higher doses (200-400 mg/day) 3
- For concentration problems and fatigue: Consider lower doses (50-200 mg/day) 3
- Timing of last dose: No later than 2:00 PM to avoid insomnia 3
Administration Options:
- Single morning dose OR divided into morning and midday doses 3, 4
- Pharmacokinetic rationale: Half-life approximately 15 hours; steady state reached after 2-4 days 3
Special Populations
Elderly Patients:
- Start at 100 mg once upon awakening 3
- Increase at weekly intervals as necessary 3
- Rationale: Pharmacokinetics show increased maximum plasma concentration and elimination half-life in elderly patients 4
Hepatic Impairment:
- Severe hepatic impairment: Reduce dose to half the recommended dose 1
- Mechanism: Modafinil is extensively biotransformed in the liver 4
Renal Impairment:
- Use caution in severe renal insufficiency due to substantial increases in modafinil acid levels 5
- Both maximum plasma concentration and elimination half-life are increased 4
Contraindications
Absolute contraindications:
- Known hypersensitivity to modafinil or armodafinil 1
Relative contraindications/cautions:
- Moderate to severe hypertension 4
- History of psychosis, depression, or mania 1
- Known cardiovascular disease (requires increased monitoring) 1
Critical Safety Warnings
Life-Threatening Dermatologic Reactions:
Discontinue modafinil immediately at the first sign of rash unless clearly not drug-related. 1
- Stevens-Johnson syndrome risk, particularly in pediatric patients 3, 1
- This is the primary reason modafinil is NOT FDA-approved for patients under 17 years of age 3
Other Serious Reactions:
- Angioedema and anaphylaxis: Discontinue if suspected 1
- Multi-organ hypersensitivity reactions: Discontinue if suspected 1
Psychiatric Monitoring:
- Monitor for development or worsening of psychiatric symptoms 1
- Consider discontinuing if psychiatric symptoms develop 1
- Use particular caution in patients with history of psychosis, depression, or mania 1
Monitoring Requirements
Cardiovascular Monitoring:
- Blood pressure and heart rate: Modest increases observed (BP: 3.6/2.3 mm Hg; HR: 6.7 bpm) 6
- Most changes occur by month 3 of treatment 6
- Increased monitoring appropriate for patients with known cardiovascular disease 1
Sleepiness Assessment:
- Assess patients frequently for degree of sleepiness 1
- Advise patients to avoid driving or dangerous activities if persistent sleepiness continues 1
Dermatologic Surveillance:
Drug Interactions
Hormonal Contraceptives:
Use alternative or concomitant methods of contraception while taking modafinil AND for one month after discontinuation. 1
- Modafinil reduces efficacy of low-dose oral contraceptives via enzymatic induction 4
CYP450 Interactions:
- Cyclosporine: Blood concentrations may be reduced 1
- CYP2C19 substrates (omeprazole, phenytoin, diazepam): Exposure may be increased 1
- Modafinil induces and inhibits several cytochrome P450 isoenzymes 5
Common Adverse Effects
Most common (≥5%): 1
- Headache (most frequent adverse event, significantly greater than placebo at 51-52% vs 36%) 7
- Nausea 1
- Nervousness 1, 3
- Rhinitis 1
- Diarrhea 1
- Back pain 1, 3
- Anxiety 1
- Insomnia 1, 3
- Dizziness 1
- Dyspepsia 1, 3
Important tolerability note: Except for headache, the tolerability profile of modafinil 200-400 mg/day was similar to placebo in 9-week trials. 4
Abuse Potential and Withdrawal
Low Abuse Risk:
- Modafinil has lower abuse potential than traditional stimulants (amphetamines, methylphenidate) 3, 4, 5
- Limited physical and psychological dependence risk 3
- No cases of abuse/addiction reported to date 5
Withdrawal Profile:
- No rebound phenomena or withdrawal syndrome after treatment cessation 4, 7
- Patients experience return of excessive daytime sleepiness to baseline levels without withdrawal symptoms 7
- This represents a significant advantage over amphetamines and methylphenidate 4
Clinical Efficacy Pearls
What Modafinil Does:
- Significantly increases daytime sleep latency (40-54% improvement) 8
- Reduces excessive daytime sleepiness 7, 8
- Does NOT adversely affect nighttime sleep parameters 7, 8
- Does NOT interfere with ability to nap voluntarily when needed 8
What Modafinil Does NOT Do:
- Does NOT suppress cataplexy 4, 7
- Does NOT cause stereotyped behavior seen with traditional stimulants 4
Long-Term Use:
- Efficacy maintained for at least 12 months 6
- Improvements in Clinical Global Impression of Change, Brief Fatigue Inventory, and Epworth Sleepiness Scale start at month 1 and are maintained throughout treatment 6
- 57% of patients completed 12 months or more of treatment in open-label extension studies 6
Common Pitfalls to Avoid
Timing error: Dosing too late in the day causes insomnia—last dose must be before 2:00 PM 3
OSA management: Failing to emphasize continued CPAP use; modafinil is adjunctive only 1
Contraceptive counseling: Not warning patients about reduced efficacy of hormonal contraceptives and need for backup methods for one month after stopping 1, 4
Pediatric use: Using in patients under 17 years without extreme caution regarding Stevens-Johnson syndrome risk 3
Dose escalation in elderly: Starting at standard adult doses rather than 100 mg 3
Hepatic impairment: Not reducing dose by 50% in severe hepatic disease 1