Methylphenidate and Attention DeficitHyperactivity Disorder in Children

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Methylphenidate and Attention Deficit/Hyperactivit
y Disorder in Children

• Missy Hobbs
• Drugs and Behavior
• Dr. Young
• Houghton College

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Table of Contents

• Methylphenidate
• Attention Deficit/Hyperactivity Disorder
• History
• Effectiveness
• Treatment
• Bibliography

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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).

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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).

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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

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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.

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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
  41 to 91 (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).

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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)

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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).

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The great debate continues

• Nurture and overdiagnosis (Diller, 1996, 12-18)
• DSM-IVs 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).

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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).

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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).

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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).

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The debate continuesSome 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.

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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 childs academic skills in areas such as
  reading, math, spelling, and written expression.
  A childs performance is measured using brief one
  to three minute reading passages and math
  worksheets that are derived from the students
  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
  students desk or is associated with an assigned
  task
• Out-of-seat behavior This occurs when the
  childs full body weight is not being supported
  by his or her chair.

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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.

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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).

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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),

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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).

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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).