1. 門診處方用藥討論 報告日期： 95.7.12 報告者：張美琪藥師 Methylphenidate(Ritalin) for the treatment of Attention deficit hyperactivity disorder

2. 處方內容

3. What is ADHD?  Psychological disorder characterized by three main traits by three main traits  Inattention  Hyperactivity  Impulsivity

4. Characteristics Poor attention and concentration Poor attention and concentration Easily distracted Easily distracted Shifting activities frequently Shifting activities frequently Day dreaming Day dreaming Forgetfulness Forgetfulness

5. Long Term Effects Anxiety Anxiety Depression Depression Stress Stress Antisocial behavior Antisocial behavior Lower educational achievement Lower educational achievement

6. Causes? Relatively unknown Strong evidence of genetic component Brain Injury Deficiencies in: –Seratonergic neurotransmitter systems –Dopaminergic neurotransmitter systems –Noradrenergic neurotransmitter systems

7. Treatment @ Stimulants @ Tricyclic antidepressants @ Bupropion @ Clonidine

8. Methylphenidate Mechanism of Action CNS Stimulant Mode of therapeutic activity is unknown Theory: Blocks the reuptake norepinephrine, but also stimulates the release of these neurotransmitters, increasing the amount of each available presynaptically.

9. Controlled, blinded studies have shown methylphenidate to be effective in increasing attention and reducing impulsivity and motor activity in hyperkinetic children (Barkley & Cunningham, 1979)(Charles et al, 1979a; Klorman et al, 1979). Improved cognitive function, motor performance, and social behavior, but had little effects on children's self esteem (Werry et al, 1980). The improvement in motor activity appears to occur in restrictive environments, and not in "free play" settings (Barkley & Cunningham, 1979). Methylphenidate use in ADHD

10. Methylphenidate FDA labeled indications  Attention deficit hyperactivity disorder  Narcolepsy

11. Methylphenidate 健保規範 1. 限使用於六歲（含）以上，依 DSM 或 ICD 標準 診 斷為注意力不全過動症患者。 2. 限對現有藥物治療之副作用無法耐受，或經現 有藥物治療一個月以上，療效不佳者使用。並 需於病歷上記載使用理由。

12. Dosage of methylphenidate Pediatric dose: 10~60 mg/day(begin with 5mg/day and titrate upward,max 60 mg/day.) Adult dose : 10-60 mg/day orally divided 2 to 3 times daily, preferably 30- 45 min before meals. Behavioral effects start within 1/2 hour to hour after ingestion, peaking at 1 and 3 hours.

13. Methylphenidate Side Effects : decreased appetite, insomnia, behavioral rebound, head and stomach aches Precautions:  Advise patients to take drug before 7 p.m to avoid possible sleep disturbance  Long-term suppression of growth in children  Cardiovascular:hypertension, tachyarrhythmia

14. Tricyclic antidepressants Mechanism of Action Inhibits the reuptake of norepinephrine or serotonin at presynaptic neuron. Drugs Imipramine Dose:2~5mg/kg/day Adverse Effects :constipation,dizziness, headache, insomnia

15. Atypical Antidepressant Mechanism of Action Inhibits neuronal dopamine reuptake,blocker of serotonin and norepinephrine reuptake. Drugs Bupropion(sustained release) Dose:100-150 mg/bid Adverse Effects :hypertension, tachyarrhythmia, insomnia

16. CLONIDINE Mechanism of Action Inhibition of norepinephrine release in brain Both methylphenidate and clonidine are beneficial in ADHD; however, the combination appears to be better than monotherapy with either agent alone in ADHD with tics. Dose Adults dose:0.1~0.3 mg/day Adverse Effects:hypotension, constipation, somnolence, tachyarrhythmia

17. Conclusion FDA labeled indication adultpediatric MethylphenidateYesYes(aged 6 y or older) Imipramine no Bupropion no Clonidineno

18. Conclusion Adult Pediatric Efficacy Effective Recommendation Class IIa Strength of EvidenceCategory B Attention deficit hyperactivity disorder FDA Labeled Indication

19. References  Doffing, Melissa A., Wolraich, Mark L.; “Pharmacokinetic Considerations in the Treatment of Attention-Deficit Hyperactivity Disorder with Methylphenidate.” CNS Drugs. 2004, 18(4), 243- 250.  Clinical practice guideline: treatment of the school-aged child with attention-deficit/hyperactivity disorder Pediatrics. 2001 Oct;108(4):1033-44  www.emedicine.com/med/topic3103.htm  micromedex