Stimulant Dosing for Narcolepsy
First-Line Treatment: Modafinil
Start modafinil at 200 mg orally once daily in the morning, with the option to increase to 400 mg daily if needed for inadequate response. 1, 2, 3
Standard Dosing Protocol
- Initial dose: 200 mg taken as a single morning dose 3
- Maximum dose: 400 mg daily, though doses above 200 mg do not consistently provide additional benefit 3
- Timing: Administer in the morning as a single dose, or split between morning and midday if late-day sleepiness persists 4, 5
- For patients experiencing residual late-day sleepiness despite satisfactory morning control, split dosing (400 mg at 7 AM plus 200 mg at noon) is more effective than 400 mg once daily 5
Special Population Adjustments
- Elderly patients: Start at 100 mg once daily upon awakening, titrate weekly as needed, with typical maintenance of 200-400 mg daily 2
- Severe hepatic impairment: Reduce dose to one-half of the standard recommendation 3
Second-Line Treatment: Armodafinil
Armodafinil 150-250 mg once daily in the morning is an alternative first-line option. 6
- Standard dose: 150 mg orally once daily in the morning 6
- Maximum dose: 250 mg daily, though evidence for additional benefit above 150 mg is inconsistent 6
- Armodafinil offers similar efficacy to modafinil with potentially longer duration of action 6
Traditional Stimulants: Reserve for Inadequate Response
Amphetamines (dextroamphetamine) and methylphenidate should be reserved for patients who fail optimized modafinil/armodafinil therapy or those with prominent cataplexy. 1
Key Considerations for Amphetamine Use
- Use only after inadequate response to modafinil at optimized doses 1
- Higher abuse potential and risk of dependence compared to modafinil 1, 7
- Requires careful monitoring for signs of abuse, diversion, cardiovascular effects, and psychiatric side effects 1
- The American Academy of Sleep Medicine provides only conditional recommendations for dextroamphetamine and methylphenidate in narcolepsy 8
Critical Monitoring Parameters
For Modafinil/Armodafinil
- Cardiovascular: Monitor blood pressure, heart rate, and cardiac rhythm when initiating or adjusting doses 2
- Dermatologic: Watch for Stevens-Johnson syndrome, particularly in younger patients (though not approved for pediatric use) 4, 3
- Contraceptive efficacy: Counsel patients that modafinil reduces oral contraceptive effectiveness 4
- Common side effects: Headache (most common), nausea, nervousness, insomnia, diarrhea, dry mouth 2, 4
For Amphetamines
- Assess for signs of abuse, dependence, or diversion at each visit 1
- Monitor cardiovascular parameters and psychiatric symptoms 1
- Evaluate for insomnia and other stimulatory effects 1
Important Clinical Caveats
- Modafinil does not treat cataplexy and requires separate management with antidepressants or sodium oxybate 2, 7
- Modafinil maintains nocturnal sleep architecture without disrupting nighttime sleep 2
- No withdrawal phenomena occur after modafinil discontinuation, unlike traditional amphetamines 7, 9
- Modafinil is Schedule IV with substantially lower abuse potential than amphetamines (Schedule II) 1, 4
- Pregnancy: Modafinil may cause fetal harm and is not recommended during pregnancy 4
- Steady-state plasma levels are reached after 2-4 days of dosing 2