Methylphenidate and Attention Deficit/Hyperactivity Disorder in Children

1. Methylphenidate and Attention Deficit/Hyperactivity Disorder in Children Missy Hobbs Drugs and Behavior Dr. Young Houghton College

2. Table of Contents • Methylphenidate • Attention Deficit/Hyperactivity Disorder • History • Effectiveness • Treatment • Bibliography

3. What is methylphenidate? • Psychostimulant: Methylphenidate is an amphetamine, a drug that augments the synaptic action of the catecholamine, dopamine, and norepinephrine neurotransmitters. These then produce direct action upon the nucleus accumbens, or the structure associated with behavioral reinforcement (Julien, 1998, 119). • Effects: Amphetamines elevate mood, induce euphoria, increase alertness, reduce fatigue, provide a sense of increased energy, decrease appetite, improve task performance, and relieve boredom. Anxiety, insomnia, and irritability are side effects (Julien, 1998, 119). • Methylphenidate accounts for 90 percent of the medication given to children for the treatment of Attention Deficit/Hyperactivity Disorder, or AD/HD (Julien, 1998, 147). • Methylphenidate is a derivative of piperidine and is structurally related to dextroamphetamine, an older drug still used to treat AD/HD (Diller, 1996, 12-18).

4. Pharmacology continued • Administration: Methylphenidate is taken orally, but cases have been reported of intranasal abuse of crushed tablets (Garland, 1998, 573-574). • Starting dose: Preschool children are given 2.5 mg during breakfast, and school-aged children are given 5 mg during breakfast. Onset of action is fifteen to thirty minutes, and the duration of action is two to four hours (University of Virginia Health Sciences Center). • Dosage adjustment: The dose is increased 5 mg every three to five days until an effect is observed. When the therapeutic effect is achieved, a second dose of the same amount can be given at lunch to control afternoon symptoms. An occasional child with severe symptoms may need a 4 PM dose to control evening symptoms. The maximum dose is .8 to 1 mg per dose (University of Virginia Health Sciences Center).

5. The Chemistry Involved • (National Library of Medicine) Chemline: • Classifications: adrenergic agent, adrenergic uptake inhibitor, central nervous system stimulant, dopamine agent, dopamine uptake inhibitor, drug/therapeutic agent, sympathomimetic • Molecular formula: C14-H19-N-O2 • Other systematic names: 2-Piperidineacetic acid, alpha-phenyl, methyl ester • Synonyms: 4311/B Ciba, Calocain, Centedin, EINECS 204-028-6, HSDB 3126, Meridil, Methyl phenidate, Methyl phenidylacetate, Methyl alpha-phenyl-alpha-(2piperidyl)acetate, Methylphenidan, Methylphenidate, Methylphenidatum, Metilfenidato, NCI-C56280, Phenidylate, alpha-Phenyl-2-piperideacetic acid methyl ester, Plimasine, Ritalin, Ritaline, Ritcher works

6. Attention Deficit/Hyperactivity Disorder • DSM-IV (American Psychiatric Association, 1994, 78) • Persistent pattern of inattention and/or hyperactivity and impulsiveness that is more frequent and severe than is typically observed in individuals at a comparable level of development. • Symptoms that cause impairment must have been present before age seven, even if diagnosis is made years later. • There must be clear evidence of interference with developmentally appropriate social, academic, or occupational functioning. • The symptoms do not occur exclusively during the course of a Pervasive Developmental Disorder, Schizophrenia, or other Psychotic Disorder and are not better accounted for by another mental disorder.

7. AD/HD in Children • Characteristics of children and adolescents with AD/HD (Heiligenstein, 1996, 41-42): • Most remain distractible, impulsive, inattentive, and disruptive throughout life. • AD/HD typically impairs school performance, limits participation in extracurricular activities, and harms social relationships. • Prevalence: • AD/HD affects between five and nine percent of children and adolescents (Corkum, Tannock, & Moldofsky, 1998, 637-646; Heiligenstein, 1996, 41-42). • Males outnumber females in ratios varying from 4:1 to 9:1 (Hardman, Drew, & Winston-Egan, 1996, 266). • Resulting use of methylphenidate: In 1995, 2.6 million people were taking methylphenidate, the vast majority of whom were children between ages five and twelve (Diller, 1996, 12-18).

8. Comorbidity with AD/HD • Learning Disabilities: AD/HD has often been associated with learning disabilities although there is not a complete correspondence in the characteristics between the two. Perception difficulties, attention problems, impulsiveness, and hyperactivity have emerged periodically as depictions of learning disabilities. The definitions of AD/HD and learning disabilities have historically overlapped and have been applied to groups of people that are very heterogeneous (Hardman, Drew, & Winston-Egan, 1996, 265-266). • Up to two thirds of elementary school-age children with AD/HD who have been referred for clinical evaluation have at least one other diagnosable psychiatric disorder such as conduct disorder, oppositional defiant disorder, learning disorders, anxiety disorders, or mood disorders, particularly depression (Julien, 1998, 145)

9. Causes of AD/HD: the great debate • Nature: • Neuroanatomical imaging and electroencephalography have identified abnormalities in the frontal lobes and the corpus callosum as implicated in causing AD/HD (Heiligenstein, 1996, 41-42). • The therapeutic effects of methylphenidate in the treatment of AD/HD have been attributed to its ability to increase the synaptic concentration of dopamine by blocking the dopamine transporters (Volkow, Wang, Fowler, Gatley, Logan, Ding, Hitzemann, & Pappas, 1998, 1325). • Familial pattern: AD/HD is more common in the fist degree biologic relatives of people with AD/HD than in the general population (American Psychiatric Association, 1994, 79). • Implications for the prescription of Methylphenidate: Study done on 206 teachers using a 44-item survey showed that teachers who advocated the use of methylphenidate to treat AD/HD were more likely to believe in genetic causal factors (Davino, 1995).

10. The great debate continues • Nurture and overdiagnosis (Diller, 1996, 12-18): • DSM-IV’s diagnostic criteria have greatly broadened the group of children who might qualify for the diagnosis; a child only needs to display symptoms in at least two environments, making parent and teacher reports sufficient to meet that criteria. • Children comprise 40 percent of those living in poverty. Also, large-scale preschool enrollment requires that younger children adhere to a more organized and less flexible social structure. • With the Individual with Disabilities Education Act of 1990, parents find that the only way to get extra help for their children is to have them labeled with a disorder. In some districts such as New York city, six times as much money is spent on a special student than on regular students, making it more likely for struggling students to be pushed to meet the criteria of a disorder in order to obtain funds for special education programs. • Nature and nurture: Neurological injury during birth complications, vitamin deficiencies, and food additives are also implicated. There are likely multiple causes (Hardman, Drew, & Winston-Egan, 1996, 266).

11. History of the prescription of Methylphenidate for AD/HD • Stimulants were first used to treat AD/HD in children and adolescents in 1937 (Heiligenstein, 1996, 41-42). Treatment began with the use of amphetamine and dextroamphetamine (Julien, 1998, 144). • Methylphenidate was first synthesized in the 1940s and was marketed as Ritalin in the 1960s. Controlled trials showed its short term benefits for “hyperactivity (Diller, 1996, 12-18).” • In the 1930s, methylphenidate and other amphetamines were prescribed as barbiturate antidotes, often at high doses. Complications due to utilizing generous amounts of multiple convulsants caused the mortality rate after moderate to severe barbiturate overdose to remain as high as 45 percent. Amphetamines fell out of favor, except for methylphenidate, which is still used to treat AD/HD (Wax, 1997, 203-209).

12. Some more about history • In the 1970s, the popular press attacked Ritalin effects as a “myth” and that it was a tool for “mind control” over children. Also, there was an epidemic of methylphenidate abuse in Sweden, causing it to be categorized as a Schedule II drug in 1971 (Diller, 1996, 12-18). • The benefits of methylphenidate in the treatment of AD/HD were slowly accepted again. The United States production of methylphenidate increased by 500 percent, or by 10,410 kilograms, between 1991 and 1995--an increase that is rare for a Schedule II Controlled Substance (Diller, 1996, 12-18).

13. Potential for Abuse: Some say “Yes.” • The school system: • In a survey, older and more experienced teachers expressed dissatisfaction both with their college training and in-service training on stimulant medication (Davino, 1995). • A survey of Florida schools demonstrated that 5, 411 doses of medication were distributed by school personnel who were not necessarily health care personnel, and methylphenidate was the most widely dispensed drug in the schools (Francis, 1996, 355-358). • Intranasal abuse of crushed Ritalin tablets reported: The vulnerability of adolescents with AD/HD to experiment with substances and the greater availability of methylphenidate make it likely that increased abuse may occur. Education of clinicians and families to be aware of the risk and to monitor more closely the dispensing of the drug is advised (Garland, 1998, 573-574).

14. The debate continues:Some say “No.” • Both methylphenidate and cocaine potentiate dopamine neurotransmitters. Methylphenidate contrasts from cocaine in its addiction potential in that the rate of its clearance from the brain is extremely slow. Therefore, the persistence of methylphenidate reduces the potential of subsequent does to induce a high (Julien, 1998, 147-148). • In regards to the Swedes: The Swedish experience of the late 1960s demonstrate the addiction potential of methylphenidate. However, there is little evidence of physical addiction to or abuse of methylphenidate when used appropriately for AD/HD (Diller, 1996, 12-18). • In Conclusion: It appears that the concern relates to a reaction some feel to the increase in distribution of methylphenidate in recent years. The emphasis lies mostly on the monitoring of and education for the dispension of methylphenidate, not on how addictive it actually is.

15. Tools • Comprehensive school-based behavioral assessment of methylphenidate effects on children with AD/HD (Gulley & Northup, 1997, 627-638) • Curriculum-Based Measurement: This tool assesses a child’s academic skills in areas such as reading, math, spelling, and written expression. A child’s performance is measured using brief one to three minute reading passages and math worksheets that are derived from the student’s current curriculum. This demonstrates sensitivity towards medication effects on academic performance as it varies across dosages with children. • Direct observation in the classroom: These observations focus on disruptive target behaviors. Target behaviors: • Inappropriate vocalization: This is any vocal sound made by the child that is not proceeded by raising a hand or acknowledgement from an adult. • Playing with objects: This is noted when the child touches any object that is not at the student’s desk or is associated with an assigned task • Out-of-seat behavior: This occurs when the child’s full body weight is not being supported by his or her chair.

16. Keep on assessing... • More tools (Gulley & Northup, 1997, 627-638): • AD/HD Rating Scale: This scale contains fourteen items that measure the symptoms of AD/HD. Each item corresponds with one of the symptoms, and the teacher rates the students’ behavior on a scale ranging from 0, meaning “not at all,” to 3, meaning “very much.” • Stimulant Drug Side Effects Rating Scale: A report on how serious the student experienced common side effects, such as headaches, stomachaches, or insomnia, that are associated with the use of stimulant medication. The teacher rates these on a scale of zero, meaning “absent,” to nine, meaning “serious.”

17. Effectiveness: Mixed Results • Possibly effective: • “Stimulant drugs improve behavior and learning ability in 60 to 80 percent of children who are correctly diagnosed (Julien, 1998, 145).” • A study done on eighteen inner city children who were diagnosed with AD/HD using a double-blind placebo trial. In an academic classroom, the children displayed significant improvements in AD/HD symptoms and aggressive behavior with methylphenidate. However, at home, parents reported few significant differences between placebo and methylphenidate on behavior ratings (Bukstein & Koklo, 1998, 340-351). • A study done on 74 children, some with AD/HD but all with conduct disorders, demonstrated through evaluations made by teachers, parents, and clinicians that methylphenidate significantly reduced behaviors specific to conduct disorders (Klein, Abikoff, Klass, Ganeles, Seese, & Pollack, 1997, 1073-1080).

18. The question remains... • Low risk: Methylphenidate, to date, does not demonstrate any long-term side effects (Heiligenstein, 1996, 41-42). Food and Drug Administration claims that there is weak potential for methylphenidate to cause terminal illnesses, including cancer (FDA Consumer, 1996, 3-4). • Possibly ineffective: • A study done on 31 children with AD/HD who were medicated with methylphenidate indicated a significantly slower response to positive reinforcement compared to those who took a placebo. The children who were medicated with methylphenidate were also more responsive to punishment. The result points to the inability of medicated children to adapt to classrooms based on positive rewards for good behavior (Arnett, Fischer, & Newby, 1996, 51-70). • A study done on 30 children with AD/HD studied the effects of methylphenidate on their ability to interpret visual and auditory nonverbal cues. The results indicated no significant improvements (Schwean, Gulka-Tiechko, & Saklofske, 1994, 49-56),

19. Multimodal approach to the treatment of AD/HD • Medication is only one aspect: Psychoeducational counseling, individual and group therapy, behavior management, cognitive therapy, biofeedback, training in social skills should all be taken into consideration when deciding a treatment for each individual child (Heiligenstein, 1996, 41-42). • Due to the growing acceptance that AD/HD has multiple causes, most reject treatment that focuses on medication exclusively. Children who received methylphenidate along with child-family counseling and special education services is the only research demonstrating long-term improvements in children treated for AD/HD (Diller, 1996, 12-18). • In a case study of a six year old boy, behavioral intervention in which behavior was socially mediated was combined with methylphenidate to treat his AD/HD. His inappropriate behavior decreased (Kayser, Wacker, & Derby, 1997, 177-180).

20. Treatment! Blah blah blah • Treating insomnia: Treatment for specific sleep problems improves attention and hyperactivity as well as family functioning and the reduction of stress levels. Behavioral treatment of these difficulties may provide symptom relief for the children. Also, exploring the impact of comorbid disorders such as anxiety disorders on the presentation of sleep disturbances in children with AD/HD should be considered in treatment (Corkum, Tannock, & Moldofsky, 1998, 637-646).