Modafinil
FDA-approved wakefulness-promoting agent (Provigil). Selective DAT inhibitor, Rx for narcolepsy, sleep apnea, shift-work disorder.
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WHAT IS MODAFINIL?
Detailed overview
Modafinil is a selective dopamine transporter (DAT) inhibitor synthesized in 1976 in France. The FDA approved it for narcolepsy in 1998, later expanding the label to obstructive sleep apnea and shift-work sleep disorder. Unlike classic stimulants, it acts via the histaminergic tuberomammillary nucleus (TMN) and the orexin system as well, showing lower euphoric affinity. Used off-label for ADHD and cognitive enhancement, although the latter is not an approved indication.
Mechanism
Selective DAT inhibitor
Half-life
12-15 hours
Onset
30-60 min
Legal status
FDA Rx (Provigil)
FDA boxed warning
Severe skin reactions (SJS/TEN/DRESS)
Safety
Side effects, stop signs, contraindications
Side effects · 7
- Headache (most common side effect, dose-dependent)
- Insomnia, sleep disturbance (especially with late-afternoon dosing)
- Anxiety, nervousness, irritability
- Decreased appetite, nausea, dry mouth
- Mild increase in blood pressure and heart rate, palpitations
- Rare but serious skin reactions (SJS, TEN, DRESS, FDA boxed warning)
- Tolerance and psychological dependence with chronic daily use
Contraindications · 6
- Serious cardiovascular disease: unstable angina, arrhythmia, left ventricular hypertrophy, prior stimulant-associated cardiac issues (FDA Provigil label)
- History of serious skin reaction (SJS, TEN, DRESS) or modafinil hypersensitivity
- Hormonal contraceptives: CYP3A4 induction reduces efficacy, backup contraception needed (during and 1 month after treatment)
- Pregnancy (FDA category C) and breastfeeding: avoid, limited safety data
- Warfarin interaction: INR monitoring needed; CYP2C19 inhibition can raise phenytoin levels
- Uncontrolled hypertension; dose reduction with severe hepatic or renal impairment
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
Modafinil: a review of neurochemical actions and effects on cognition
Minzenberg MJ, Carter CS.
Modafinil for cognitive enhancement in healthy non-sleep-deprived
Battleday RM, Brem AK.
Modafinil, long-term safety in narcolepsy
Mitler MM et al.
Mechanisms of modafinil: A review of current research.
Gerrard P, Malcolm R
Treatment of narcolepsy: pharmacological strategies
Pizza F et al.
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The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.