Methylphenidate and Attention DeficitHyperactivity Disorder

1
Methylphenidate andAttention Deficit/Hyperactivi
ty 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 worlds 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).

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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 contd

• 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).