Products
Modafinil is commercially available in tablet form (CH: Modasomil-100, Modafinil-Acino, DL: Vigil, USA: Provigil). It has been approved in the EU since 1992, in the US since 1998, and in many countries since 2000.
Structure and properties
Modafinil or 2-benzhydrylsulfinylacetamide (C15H15NO2S, Mr = 273.35 g/mol) is a racemate and exists as a white crystalline powder that is practically insoluble in water. The -enantiomer armodafinil is also available in the United States (Nuvigil). The enantiomers are pharmacologically very similar but differ in pharmacokinetics. Armodafinil has a significantly longer half-life than the -enantiomer. Modafinil has no structural similarities to the amphetamines. Adrafinil is a prodrug of modafinil that is no longer commercially available.
| Modafinil | Armodafinil |
Effects
Modafinil (ATC N06BA07) centrally promotes alertness and attention and increases motor activity. It has effects on several neurotransmitter systems; the exact mechanism of action is unknown. Modafinil is pharmacologically distinct from other stimulants. Whether it affects mood and euphoria is controversial. For example, the FDA writes: “Modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other CNS stimulants in humans.” On the other hand, numerous publications draw attention precisely to a lack of euphoric effect.
Indications
Modafinil is approved in many countries for the treatment of narcolepsy (“sleeping sickness”). In other countries, it is also approved in the indication of shift work sleep disorder. It is taken before night work and keeps you awake. In July 2010, the European Medicines Agency (EMA) recommended that the drug be used only for the treatment of narcolepsy and no longer for idiopathic hypersomnia, sleep apnea syndrome and shift work due to the adverse effects and potential for abuse. Swissmedic later followed this recommendation. There are numerous potential uses in the literature, ranging from motion sickness to Parkinson’s disease, but modafinil has not been cleared by regulators for this purpose.
Abuse
Modafinil keeps you awake and can be abused as a performance enhancer, smart drug, party drug, and doping agent. It is on the doping list. Whether it causes euphoria is controversial (see above).
Dosage
According to the SmPC. The drug is taken as a stimulant in the morning, possibly additionally at noon, or 1 hour before shift work. The intake is independent of meals. The maximum daily dose is 400 mg.
Contraindications
Modafinil is contraindicated in hypersensitivity, concomitant treatment with prazosin (not commercially available in many countries), past drug dependence, drug or alcohol abuse, during pregnancy and lactation, severe hypertension, a history of left ventricular hypertrophy, and in patients who have responded to stimulants with symptoms of mitral valve prolapse. It must not be used in children and adolescents. For complete precautions, see the drug label.
Interactions
Modafinil induces CYP3A4, CYP1A1, and CYP2B6 and inhibits CYP2C19 and CYP2C9; corresponding drug-drug interactions are possible.
Adverse effects
Very common adverse effects include headache and nervousness. Central disturbances, cardiovascular disturbances, and digestive problems are common. Modafinil has come under criticism because it can rarely cause severe hypersensitivity reactions and skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis, as well as neuropsychiatric disorders such as psychosis, mania, delusions, hallucinations, and suicidal ideation. These side effects may occur but affect very few patients.
