1 門診案例討論 ~ Methylphenidate Use in Narcolepsy 藥師 : 郭子瑋 日期 :

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3 Narcolepsy (1) NARCOLEPSY is a neurological disorder that effects the regulation of sleep and wakefulness. The primary symptom is excessive daytime sleepiness. These attacks can last for less than 30 minutes to as long as several hours (Campbell, 1981). Approximately 70% of the patients with narcolepsy also experience CATAPLEXY during the day (Zarcone, 1973).

4 Narcolepsy (2) Cataplexy is related to REM sleep. There are two parts to REM sleep: 1) dreaming with rapid eye movement, and 2) loss of muscle tone. Usually triggered by emotions (anger, laughter, surprise, fear), patients with cataplexy go directly into REM sleep, lose muscle tone, but remain fully conscious. These daytime attacks can last from several seconds to several minutes (Campbell, 1981).

5 Narcolepsy Syndrome Patients with the narcolepsy syndrome may also exhibit other symptoms. These include AUTOMATIC BEHAVIOR, SLEEP PARALYSIS, HYPNAGOGIC HALLUCINATIONS, and SLEEP DISTURBANCES. Automatic behavior is described as lack of awareness when performing routine tasks (Campbell, 1981).

6 Clinical findings Sleep attacks, cataplexy, hypnagogic hallucinations, sleep paralysis, family history of condition Interpretation Irresistible episodes of daytime onset of sleep and motor paralysis

7 Methylphenidate (10 to 60 milligrams/day) is indicated for the treatment of narcolepsy in adults and children. It has been shown to improve performance and ability to stay awake (Prod Info RITALIN(R) oral tablet, RITALIN-SR(R) oral tablet, 2004; Francisco & Ivanhoe, 1996; Mitler et al, 1987a; Mitler et al, 1986c; Honda et al, 1979a). Methylphenidate use in Narcolepsy (1)

8 Summary: - Methylphenidate is effective for the treatment of narcolepsy in adults and children 6 years and over - Methylphenidate improves performance and ability to stay awake - Methylphenidate has been used for various diseases which exhibit hypersomnia as a prominent clinical feature Methylphenidate use in Narcolepsy (2)

9 Central nervous system (CNS) stimulant—Although the primary mechanism is largely unknown, the effects of methylphenidate appear to be mediated by blockage of the reuptake mechanism of dopaminergic neurons. In narcolepsy, methylphenidate appears to act at the cerebral cortex and subcortical structures, including the thalamus, to produce CNS stimulation, resulting in increased motor activity, increased mental alertness, diminished sense of fatigue, brighter spirits, and mild euphoria. Methylphenidate --- Mechanism of action/Effect:

10 Dosage of Methylphenidate Narcolepsy: Adults~ immediate release, mg/day ORALLY divided 2 to 3 times daily, preferably min before meals max:60mg/day (Food may increase oral absorption )

11 Pharmacodynamic of Methylphenidate onset: immediate release tablet ~2hrs duration: 3-6hrs absorption: readily half-life: 2-4hrs time to peak: 6-8hrs

12 Conclusion Narcolepsy FDA Labeled Indication Overview AdultPediatric FDA Approvalyesyes (age 6 years and older) Efficacy Effective Recommendation Class IIa Strength of EvidenceCategory B