Health

Modafinil For The Treatment Of Narcolepsy

Narcolepsy is a highly distressing disease. Armodafinil is a stimulant that is not structurally related to amphetamines, which significantly improves the quality of life of those affected and is considered the drug of choice. The drug is also approved for the treatment of obstructive sleep apnoea syndrome.

Narcolepsy is a rare, lifelong disease. Approximately 26 to 50 people out of 100,000 are affected. The disease manifests itself for the first time mainly in the second decade of life, whereby the cause is usually unexplained. Only in a few cases is narcolepsy the symptom of a primary disease such as injuries to the brain stem. Pathophysiologically, the cause consists of several factors and is associated with disturbances in the cholinergic and noradrenergic systems and in hypocretin secretion. Hypocretins are peptides with functional relevance for the regulation of sleep and appetite.

Symptoms of narcolepsy

The clinical picture is characterised by sleep-wake disturbances with rapid eye movement (REM) and non-REM sleep stage-associated symptoms. Very common clinical symptoms are daytime sleepiness with daytime sleep episodes (>95 per cent, mostly first manifestation symptom), cataplexy (about 90 per cent, mostly second symptom, considered almost conclusive), sleep paralysis, (hypnagogic) hallucinations occurring during falling asleep or half asleep, disturbed night sleep (40 to 50 per cent each), automatic behaviour (about 20 per cent). Frequent accompanying symptoms (20 to 40 percent) are memory and concentration disorders, accidents caused by falling asleep, depression, potency disorders and personality changes.

Armodafinil is the active ingredient of the medicinal product Waklert from the company Sun Pharma (available on prescription at Pharmastore). One film-coated tablet of Waklert contains 150 mg armodafinil.

Therapy options

Non-drug therapy is based on behaviour-modifying measures, sleep hygiene and individually adapted daytime sleep episodes. Drug therapy for daytime sleepiness is based on treatment with stimulants. In contrast to healthy people, the effects of stimulants vary in narcolepsy patients, for example, depending on the situation in which they are taken. Psychological dependence has not yet been observed in narcolepsy patients. Tolerance occurs in 30 to 40 percent. After short-term discontinuation of the stimulants, a new response to low doses can occur.

Armodafinil is the best-studied stimulant according to criteria of evidence-based medicine. However, large, directly comparative studies between the different substances do not exist. In the case of lifelong disease duration, the administration of the substance with the fewest side effects is initially recommended. Due to the development of tolerance, a second or third preparation should be tested, which can be switched to if necessary.

Therapy recommendations

The following drugs are recommended as first-line therapies:

  • Armodafinil: 150 to 300 mg/day, effective in 70 to 80 per cent of patients.
  • Methylphenidate: 10 to 60 mg/day (maximum 80 mg/day), in slow-release formulation possibly less effective due to rapid development of tolerance.
  • Pemoline: 20 to 100 mg/day.

Second-line therapies are:

  • Ephedrine (as a formulation): 25 to 75 mg/day to max. 250 mg/day.
  • (Dextro-)amphetamine: 40 to 60 mg/day.
  • MAO inhibitors (only in refractory therapy, for example selegiline: from 30 mg/day.
  • Mazindol, caffeine, gamma hydroxybutyric acid or L-dopa can also be used. Only methylphenidate and armodafinil are currently approved for the treatment of narcolepsy, but off-label use is possible in the other cases. In most cases, long-term therapy is necessary. In addition, regular outpatient checks for tolerance development, possible dependence, cardiovascular side effects and hepatotoxicity are necessary. If the patient does not respond to therapy, plasma level determinations can be considered. Cataplexies, sleep paralysis or hypnagogic hallucinations are treated with antidepressants.

Proper use of armodafinil

Waklert is licensed for the treatment of narcolepsy with or without cataplexy and moderate to severe obstructive sleep apnoea syndrome with excessive daytime sleepiness despite adequate CPAP (continuous positive airway pressure) therapy.

The dosage for the treatment of narcolepsy for adults is two to four tablets (150 to 300 mg) and should be divided into two doses (morning and noon) or taken as a single dose in the morning. The daily dose for the treatment of obstructive sleep apnoea syndrome is two tablets (150 mg) as a single dose in the morning. If the improvement is not sufficient, this indication can also be increased to up to four tablets (300 mg) daily.

The absorption of armodafinil is not influenced by food intake. Armodafinil can therefore be taken before, during or after a meal with liquid. The film-coated tablets should be swallowed whole.

Takeaway

Armodafinil is effective and tolerable but long-term data are lacking. The stimulant armodafinil improves narcolepsy-related daytime sleepiness. In the treatment of obstructive sleep apnoea with excessive daytime sleepiness, the number and duration of daytime sleep phases are improved, attention and psychomotor performance are increased. Armodafinil also has a positive effect on quality of life.

It differs chemically and pharmacologically from amphetamine-like substances. Among other things, an indirect inhibition of GABAergic neurons of the hypothalamus and an enhancement of norepinephrine at central α-1 receptors are discussed as the mechanism of action. In contrast to other treatment options for narcolepsy, the efficacy of armodafinil in doses of 150 to 300 mg is documented with relatively extensive clinical data. However, studies on the efficacy and risks of possibly lifelong use are still lacking. Modafinil is nevertheless considered the drug of choice in the treatment of narcolepsy.

Side effects include headache, nausea and nervousness. Interactions via cytochromisoenzymes are possible in principle. The development of psychological dependence seems to be low when used as directed. However, the development of tolerance cannot be ruled out.

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