Modafinil in narcolepsy

Compiled from US. Modafinil in Narcolepsy Multicenter Study Group and Standard of Practice Committee of the American Sleep Disorders Association. Pradice parameters for the use of stimulants in the treatment of narcolepsy. Seep 1994 17 348-351. 

Modafinil is a stimulant medication used to improve wakefulness in patients with narcolepsy, obstructive sleep apnea/hypopnea syndrome (as adjunct to standard treatments for the underlying disorder), and shift work sleep disorder. Controlled and open trials provided data on the efficacy and safety of modafinil in patients with narcolepsy (Besset et al. 1996 Billiard et al. 1994 Broughton et al. 1997 Mitler et al. 2000 U.S. Modafinil in Narcolepsy Multicenter Study Group 1998, 2000). Modafinil has a long duration of action and low potential for dependence and may be a reasonable first choice in the treatment of mild to moderate narcolepsy (Silber 2001). There is also considerable interest in the potential use of modafinil in the treatment of ADHD, and studies are in progress. 

U.S. Modafinil in Narcolepsy Multicenter Study Group Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. Neurology 54 1166-1175, 2000 Wernicke JF, Kratochvil CJ Safety profile of atomoxetine in the treatment of children and adolescents with ADHD. J Clin Psychiatry 63 (suppl 12) 50-55, 2002... 

Sangal RB, Mitler MM, Sangal JM and US modafinil in narcolepsy multicenter study group. MSLT, MWT and ESS indices of sleepiness in 522 drug-free patients with narcolepsy. Sleep Res 1997 26 492. 

U.S. Modafinil in Narcolepsy Multicenter Study Group. Randomized trial of modafmil for the treatment of pathological somnolence in narcolepsy. Ann Neurol 1998 43 88-97. 

Administer the ESS at each visit to monitor progress with modafinil or stimulant therapy. Unfortunately, EDS in narcolepsy patients rarely is fully reversed. 

Comparisons of modafinil with agents that have proven effective in narcolepsy, including methylphenidate, pemoline, and dextroamphetamine, are needed to clarify its relative safety and efficacy, and place in therapy... 

Besset A, Chetrit M, Carlander B, et al Use of modafinil in the treatment of narcolepsy a long-term follow-up study. Neurophysiol Clin 26 60-66, 1996... 

Broughton RJ, Fleming JA, George CF, et al Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Neurology 49 444-451, 1997... 

Modafinil is a wake-promoting agent whose specific biochemical mechanism of action is obscure. It increases brain concentrations of dopamine after chronic administration in animals but has no overtly stimulant effect like amphetamines. It appears to have a slow onset and its action lasts 8-12 h abuse potential is very low. Modafinil is used in narcolepsy and other hypersomnias and has also been studied in normal people who need to stay awake for long periods and fimction well. 

In narcolepsy, patients usually need a stimulant for their hypersomnia and a TCA or SSRI for their cataplexy, so care should be taken when combining these. Dexamfetamine and methylphenidate must not be given with MAOIs. There is potential for interaction between methylphenidate and TCAs (hyperteirsion) and SSRI antidepressants. It appears that modafinil, methylphenidate and dexamfeta-mine may themselves be combined without adverse outcome (modafinil is occasionally used regularly and dexamfetamine added intermittently when peak alertness is particularly critical). Modafinil accelerates the metabolism of oral contraceptives, reducing their efficacy. 

Modafinil was effective in narcolepsy in a 9-week, randomized, placebo-controlled, double-bhnd, 21-center trial in 271 patients (4). During treatment withdrawal, the patients did not have symptoms associated with amphetamine withdrawal. Nausea and rhinitis were significantly more common in the treatment group in contrast, in a previous multicenter study in the USA there was a higher incidence of headache (5). Modafinil was also effective in the treatment of somnolence due to pramipexole in a patient with Parkinson s disease (6). 

The traditional analeptics are a group of potent and relatively nonscicctivc CN.S stimulants. Tire convulsive dose lies near their analeptic dose. They can be illustrated by picrotoxinin and pcntyicnctctrazole. Both are obsolete as drugs but remain valuable research tools in determining how drugs act. Newer agents, modafinil and doxapram, are more. selective and have use in narcolepsy and as respiratory stimulants. 

The Food and Drug Administration approved modafinil in 1998 to treat excessive daytime sleepiness associated with narcolepsy and other sleep disorders. Sadna Kohli, Ph.D., MPH, at the University of Rochester, and colleagues wanted to see if the drug, which is marketed to improve wakefulness, would help with persistent fatigue in patients who had been treated for cancer. 

The mode of action of modafinil, a new arousal-promoting compound used in the treatment of sleepiness associated with narcolepsy, is not fully understood. 

Modafinil (Provigil). The newest stimulant, modafinil, is not, pharmacologically, a true stimulant. Nevertheless, it is an effective treatment for narcolepsy at doses from 200 to 400mg/day. Several studies indicate that modahnil has little potential for abuse and is easier to tolerate than other stimulants. Modafinil has been studied in the treatment of ADHD. Though not approved for marketing by the FDA at the time of this writing, it may gain the indication in the near future. 

The recommended dose of modafinil is 200 mg/day for the treatment of excessive daytime sleepiness associated with narcolepsy however, doses of 400 mg/day are FDA-approved. While there is evidence that the higher dose is well tolerated, it has not been established that it confers additional therapeutic benefit (196). In sleep-deprived subjects, doses of 600 mg/day have been administered, but the preponderance of evidence suggests that 300M00 mg/day is probably sufficient and less likely to produce unwanted side effects. 

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