Methylphenidate and Attention Deficit/Hyperactivity Disorder

1. MethylphenidateandAttention Deficit/Hyperactivity Disorder by Lisa Taylor Drugs and Behavior Dr. Paul Young

2. Amphetamine-like drugs • Classified as stimulants and have been used to treat AD/HD in children and adolescence since 1936 (Julien, 1998, 145). • Treatment started with the use of amphetamine and dextroamphetamine (Julien, 1998, 145). • Used to elevate mood, induce euphoria, increase alertness, reduce fatigue, decrease appetite, improve task performance and relieve boredom (Julien, 1998, 119).

3. Attention Deficit Hyperactivity Disorder • ADHD is the most common psychological disorder of childhood, estimated to affect 3% to 9% of school-age children. • ADHD is characterized by problems with attention, learning, impulse control, and hyperactivity. • 1.29 million children with ADHD are being treated with stimulant medication. • (Julien, 1998, 144).

4. AD/HD continued • 40-60 % of affected individuals with AD/HD have persisting symptoms beyond childhood into adulthood. • Comorbidity with conduct disorder, oppositional defiant disorder, learning disorders, anxiety disorders and mood disorders exists within 2/3 of elementary school-age children with ADHD • (Julien, 1998, 144).

5. ADHD and school peformance • High risk relative to normal population with respect to scholastic and social failure in school settings (DuPaul & Eckert, 1997, 5). • Methylphenidate results in immediate improvements on various academic type tasks (reading performance, classroom seatwork, academic performance and tasks) (Carlson & Bunner, 1993, 184).

6. Methylphenidate (Ritalin) • Ritalin has been used since 1954 to treat ADHD and has historically has had a high safety record. • Distribution of methylphenidate in the United States increased dramatically from 1990-95 (Morrow, Morrow & Haislip, 1998, 1121). • The U.S produces 90% of the world’s Ritalin (Diller, et al., 1997, 730). • Ritalin is prescribed for children at least age 5 into adulthood (Borgstadt, et al., 1998, 125).

7. Predisposition to AD/HD • When the parents have experienced affective disorders, their children are at a higher risk of suffering from ADHD. • Youth coming from families that suffer familial dysfunction or are disorganized are at high risk for ADHD. • There is a possible genetic component • (Julien, 1998, 145).

8. Genetically predisposed? • A research team from Duke University found that hyperactivity symptoms were caused by too little serotonin in addition to high concentrations of dopamine. • The research team has gathered information from a genetically modified mouse • dopamine transporter gene eliminated -- high concentrations of extracellular dopamine concentrations -- good response to Ritalin • (Berger, 1999, 212).

9. Other etiology • Frontal lobe theory • children with ADHD have dysfunctional or disproportionate sizes in their frontal lobe • Parietal lobe theory • differences in right parietal lobe in children is a possible secondary cause • (Aman, Pennington & Roberts Jr., 1998, 956).

10. Genetic contributions: twin studies • monozygotic twins and dizygotic twins were studied in which one of the twins had ADHD • In these case of identical twins , 55%- 92% of the time, when one twin had ADHD, the other would develop the condition • (Barkely, 1998, 66).

11. Pharmacology and AD/HD • Stimulant drugs improve behavior and learning ability in 60-80% of children correctly diagnosed. • The primary psychopharmacological agents are the CNS stimulants. • The prototype drugs are dextroamphetamine, methylphenidate and pemoline (Julien, 1998, 145). • Methylphenidate is considered to be the drug of choice (Volkow et al, 1998, 1325).

12. Pharmacokinetics of Ritalin • Oral administration • adverse effects of chewing methylphenidate(Pleak, 1995, 811). • Rapid onset • Short duration: administered at breakfast and lunchtime • not administered in evening to permit the blood level to drop, allowing for normal sleep. • Short half-life can be troublesome for some children (Julien, 1998, 147).

13. Drug effects • Because Ritalin resembles the amphetamines and cocaine there is great potential for reinforcing effects and abuse. • The rate of clearance from the brain is extremely slow and can be considered a limiting factor in promoting its frequent self-administration. • (Julien, 1998, 147).

14. Pharmacodynamics of Ritalin • Therapeutic effects of methylphenidate are due to its ability to increase the synaptic concentration of dopamine • This increase is performed by blocking dopamine transporters • Levels of dopamine transporter blockade achieved at therapeutic doses in treatment are not known • (Volkow, et al., 1998, 1325).

15. Side effects • Stimulant effects include: weight loss, increased somatic complaints, and parent/teacher reports of reduced inattentiveness, aggressiveness and oppositionality. (Smithee et al., 1998, 233). • Insomnia, decreased appetite, stomachaches, and headaches are the most commonly reported by children on stimulants (Efron, Jarman & Barker, 1998, 662).

16. Other effects • Dizziness • anxiousness • irritability • proneness to crying • (Efron, Jarman & Barker, 1997, 662).

17. Growth hormone effects? Why? • Decreased appetite leads to low weight gain causing slow growth • Alterations in dopaminergic pathways have a role in the pathogenesis of ADHD • Association between growth failure and ADHD may have an endocrine cause • Methylphenidate may have direct effects on cartilage metabolism. • (Rao, et al., 1998, 497).

18. Co-morbidity • High comorbidity between learning disabilities and ADHD • social perception problems and poor social skills result • family relationship problems • trouble interacting with teachers • fewer friends • low self-esteem • (Bolen, et al., 1998, 125).

19. An alternative to Ritalin • Methylphenidate labeled with a radioactive tracer, carbon 11, small amounts injected into 2 volunteers. • Using PET scans they found that the form of MPH known as the d-threo enhancer targets the basal ganglia, the part of the brain involved in therapeutic effect • l-threo enantiome delivers itself non-specifically throughout entire brain

20. d-threo/l-threo entantiomes cont’d • a proposal was made at the American Medical Society for using the d-threo enantiomer alone • l-threo is less effective and may be the contributor of side effects • d-threo appears to block dopamine uptake better than the l-threo form • (Wu, 1998, 213).