What is Provigil (modafinil) and are there similar medications?

Modafinil (Provigil) and Similar Medications

Modafinil (Provigil) is a wakefulness-promoting agent FDA-approved for excessive daytime sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder, with similar medications including armodafinil, which is its longer-lasting isomer. 1, 2

Mechanism of Action and Pharmacokinetics

• Modafinil has a novel mechanism of action that is pharmacologically distinct from traditional CNS stimulants like amphetamine, dexamphetamine, and methylphenidate 3
• Its precise mechanism is not fully understood but likely involves enhancing activity in the hypothalamic wakefulness center, activating tuberomammillary nucleus neurons that release histamine, and activating other hypothalamic neurons that release orexin/hypocretin 4
• Modafinil has a half-life of approximately 15 hours, with steady state reached after 2-4 days of dosing 2
• Unlike traditional stimulants, modafinil has less abuse potential and does not typically disturb nighttime sleep patterns 4, 5

Dosing Information

• The maximum total daily dose of modafinil is 400 mg per day, typically administered as a single dose in the morning or divided into two doses 2
• Higher doses (200-400 mg/day) may be more effective for treating sleepiness, while lower doses (50-200 mg/day) may be more appropriate for concentration problems and fatigue 2
• For elderly patients, a starting dose of 100 mg once upon awakening is recommended, with potential increases at weekly intervals as necessary 2

Similar Medications

• Armodafinil (Nuvigil): The longer-lasting R-isomer of modafinil, also FDA-approved for excessive sleepiness associated with narcolepsy, obstructive sleep apnea, and shift work sleep disorder 4, 6
• Dextroamphetamine: A more potent psychostimulant than methylphenidate, used for treating fatigue but with higher abuse potential than modafinil 4
• Methylphenidate: A traditional psychostimulant used for attention deficit disorders and sometimes for fatigue, but with higher abuse potential than modafinil 5

Clinical Applications

• FDA-approved uses: Treatment of excessive daytime sleepiness associated with:

  • Narcolepsy 1
  • Obstructive sleep apnea/hypopnea syndrome (as adjunctive therapy with CPAP) 1, 3
  • Shift work sleep disorder 1, 7

• Off-label uses (evidence varies):

  • Cancer-related fatigue 4
  • Multiple sclerosis-related fatigue 4
  • Adjunctive treatment for depression 8
  • Attention-deficit disorder 5
  • Cognitive enhancement 6
  • Cocaine dependence and withdrawal 5

Safety Profile and Side Effects

• Most common adverse effects (≥5%) include:

  • Headache, nausea, nervousness, rhinitis, diarrhea 4
  • Back pain, anxiety, insomnia, dizziness, and dyspepsia 4, 2
  • Increased blood pressure and heart rate 6

• Serious but rare side effects:

  • Serious rash or allergic reactions that may affect liver or blood cells 1
  • Stevens-Johnson Syndrome (particularly in children) 6
  • Modafinil is not approved for use in children for any medical condition 1

Important Considerations

• Modafinil may reduce the effectiveness of hormonal contraceptives, requiring alternative birth control methods 1
• It is classified as a federally controlled substance (C-IV) due to potential for abuse, though this risk is lower than with traditional stimulants 1, 4
• Drug interactions are possible with medications metabolized by the liver 1
• While modafinil improves measures of sleepiness, it does not generally normalize them completely 7