Narcolepsy in children

MPH is an amphetamine-like prescription stimulant commonly used to treat Attention Deficit Hyperactivity Disorder (ADHD) and narcolepsy in children and adults. LC/APCI-MS enantiomeric separations of racemic MPH (Ritalin ) were reported using a commercially available vancomycin CSP [111-113]. 

Challamel MJ, Mazzola ME, Nevsimalova S, Cannard C, Louis J, Revol M (1994) Narcolepsy in children. Sleep 17 S17-S20... 

Marcus CL, Trescher WH, Halbowere AC, Luiz J (2000) Secondary narcolepsy in children with brain tumor. Sleep 25 435-439... 

Miller E, Andrews N, SteHitano L, Stowe J, Winstone AM, Shneerson J, et al. Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/HINI2009 influenza vaccine retrospective analysis. BMJ 2013 346. 

Amphetamines (speed sulph, sulphate, uppers, wake-ups, billy whizz, whizz, whites, base) are synthetic stimulants which as medicines have been formed into a variety of tablets. Their current medical use is very limited and in fact only dexamphetamine sulphate, Dexedrine, is now available for use solely in the treatment of narcolepsy. The only other amphetamine available for medical use is methylphenidate (Ritalin) for the treatment of attention deficit syndrome in children. As a street drug, amphetamine usually comes as a white, grey, yellowish or pinky powder. The purity rate of street powders is less than 10%, the rest being made up of milder stimulants such as caffeine, other drugs such as paracetamol or substances like glucose, dried baby milk, flour or talcum powder. 

Methylphenidate (Ritalin, Concerta, Focalin). Methylphenidate was introduced in the late 1950s and is now the most widely used prescription stimulant. It was first used to treat ADHD in children but is also effective for narcolepsy. Like dextroamphetamine, methylphenidate should be started at 5 mg per dose given two to three times each day with meals. The average effective dose is 20-30 mg/day, but some patients require as much as 60 mg/day. The benefit of methylphenidate should also be apparent on the first day or so, and the dose can be increased every 5-7 days as needed. Focalin dosing is approximately half that of methylphenidate. 

Dextroamphetamine should be used with caution and only upon medicinal indication in treating narcolepsy, consequences of encephalitis, and other illnesses accompanied by apathy, drowsiness, asthenia, for temporary increase of physical and mental capacity, in treating attention deficit disorder in children, and in treating obesity.Synonyms of this drug are D-amphetamine, dexamphetamine, dexalone, tempodex, zenidex, and many others. 

Pemoline is used for narcolepsy and for relieving drowsiness, as well as in treating attention-deficit disorder in children. Synonyms of this drug are tradon, deltamine, volital, phenoxazole, antimeran, cylert, and others. 

There is no place anymore for the amphetamines in our therapeutic armamentarium. The only indications for the other stimulants, modaflnil and methylphenidate, are respectively narcolepsy and the attention deflcit disorders (ADHD) and hyperactivity syndromes in children. Their mechanisms of action include enhanced release of dopamine and norepinephrine, re-uptake inhibition of dopamine and norepinephrine and to some extend monoamine oxidase inhibition. 

Stimulants are a class of psychoactive medications approved by the U.S. Food and Drug Administration (FDA) for use in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents and narcolepsy. A hst of available stimulants is shown in Table 6-1. 

AmiShsEfteypitesiare scheduled drugs which have a definite therapeutic use in the treatment of narcolepsy and attention deficit disorder (ADD) in children. Ritalin , Dexedrine and, to a lesser extent, Cylert are used in the treatment of ADD. It is believed that ADD is caused by a deficiency of brain NE and DA which normally help a child to focus his or her attention on... 

Similarly, persistent sleep problems have also been associated with learning difficulties throughout the elementary-high-school years (116). Studies of excessive sleepiness in children and adolescents due to DSPS, narcolepsy, or sleep apnea have also reported negative effects on learning, school performance, and behavior (117-119). Students who get more sleep and maintain more consistent school/weekend sleep schedules may obtain better grades because of their ability to remain alert and to pay greater attention in class and on homework. 

The usual starting dose for the treatment of ADHD in children over 5 years of age is 37.5 mg/ day, increased gradually by 18.75 mg/week until the desired response is reached. The usual therapeutic dose range is from 56.25 to 75 mg/day, with a maximum dose of 112 mg/day (57). Since pemoline is not approved for the treatment of narcolepsy, dosage recommendations for this indication are not readily available however, in the subsequent section, dosage information can be extrapolated from a small number of sleep deprivation studies. 

Guilleminault C, Pelayo R (1998) Narcolepsy in prepubertal children. Ann Neurol 43 135-142... 

Modafinil another wakefulness promoting agent with an unknown mechanism of action used for narcolepsy in adults and being studied for use in children at present dose range is 1 Of MOO mg/day divided bid. Side effects include headaches, anxiety, nausea and nervousness. 

Methylphenidate was synthesized in 1944 in Europe in an unsuccessful attempt to create a stimulant that would not produce addiction or tolerance (Figure 1.1). Introduced in the United States in 1955, it was first approved by the FDA for the treatment of drug-induced lethargy, mild depression, and narcolepsy. In the early 1960s, the drug was first marketed under the name Ritalin to improve memory in elderly patients and to treat several behavioral problems in children. 

The most important problem encountered with amphetamines is abuse and the development of dependence. The most rapid amfetamine epidemic occurred in Japan after World War II, where there had been little or no previous abuse (83). Although a high proportion of amfetamine users probably already have emotional and social difficulties, sustained abuse can result in serious psychiatric complications, ranging from severe personality disorders to chronic psychoses (84,85). Whereas signs of intense physical dependence are not thought to occur (SED-9, 9), withdrawal may be associated with intense depression (SED-9, 9) (86), and relapses in psychiatric disorders have often been noted. Some countries in which the problem became widespread banned amphetamines, and Australia restricted their use to narcolepsy and behavioral disorders in children. Amfetamine dependence developed into a serious problem in the USA (and to a lesser extent in the UK), where it followed the typical pattern of drug dependence (SED-9, 7,10). 

Dextroamphetamine is a sympathomimetic amine that is used in narcolepsy and in attention-deficit disorder (ADD) in children. Dextroamphetamine releases norepinephrine and, in high doses, also dopamine. It is absorbed from the GI tract, metabolized in the liver, and excreted unchanged in the urine. Acidification of urine shortens amphetamine s half-life, whereas alkalinization of urine prolongs it. The accumulation of hydroxy metabofite of amphetamine has been thought to cause amphetamine-induced psychosis. Therapeutic doses of amphetamine may cause insomnia, tremor, and restlessness, and toxic doses of amphetamine may cause mydriasis, hypertension, and arrhythmia. Chlor-promazine is an excellent antidote in amphetamine toxicity. 

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... 

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