2.  Describe the clinical presentation of ADHD
and how the disorder is diagnosed.
 Compare and contrast the first-line
treatments of ADHD.
 Analyze the clinical trials on bupropion
versus methylphenidate for ADHD.
 Determine bupropion’s place in therapy.

3.  ADHD: Attention Deficit Hyperactivity
Disorder
 NT: neurotransmitter
 QOL: quality of life
 CV: cardiovascular
 MOA: mechanism of action
 ADR: adverse drug reactions
 CI: contraindications

4.  Attention Deficit Hyperactivity Disorder
 One of the most prevalent psychiatric
illnesses among children and adolescents in
the USA (8.7%)
 Etiology unknown; low levels of NTs
 Risk Factors:
› genetics
› maternal exposure to lead/PCBs, smoking,
alcohol

5.  Greatly decreases QOL
 Linked to:
› low self-esteem, difficulties with social
interactions, and poor academic performance
 Often persists into adulthood, with serious
consequences
 < 33% of patients are treated

7.  Careless mistakes
 Easily distracted/bored
 Trouble staying focused on tasks
 Disorganized
 Loses things
 Forgetful
 Does not listen when spoken to

8.  Inability to stay seated
 Fidgeting/squirming
 Restlessness
 Excessive talking
 Impatience with waiting
 Interrupts/intrudes on others
 Low stress tolerance/emotional instability

9.  ≥ 6 symptoms (per domain) present for ≥ 6
months
› in multiple settings
› several before 12 years of age
 Not due to another mental disorder
 Interfere with functioning/daily life
 Interviews, diagnostic rating scales,
academic records, physical exam

10.  Combined Presentation
› Inattention + hyperactivity/impulsivity
 Predominately Inattentive Presentation
› Inattention
 Predominately Hyperactive-Impulsive
› Hyperactivity/Impulsivity
 *Symptoms/presentation can change over
time

12.  No cure for ADHD
 Medication +/- behavioral therapy
 Medications reduce symptoms, improve
functioning, and QOL
› Long-term benefits are unknown

13.  Mainstay of treatment, used for decades
› Methylphenidate, amphetamine,
dextroamphetamine, dexmethylphenidate
› For age 6 and older
 Equally effective; patients may respond to
one drug better than another
 C-II; concerns with drug abuse/dependence

14.  The gold standard of treatment
› Brand names: Concerta, Daytrana, Ritalin,
Metadate, Methylin
› Generic available
› Oral, transdermal patch
 MOA: CNS stimulant; blocks pre-synaptic
reuptake of NE and dopamine

15.  ADR: decreased appetite, insomnia,
stomach upset, weight loss
› Pregnancy Category C
› No renal/hepatic dosing
 Warning: Associated with CV events
 See provider: chest pain, shortness of breath
 Use the lowest effective dose
 CI: serious heart problems
› Evaluate for cardiac disease prior to start

16.  Immediate-Release
› 5 mg bid prior to breakfast and lunch
 Increase by 5-10 mg daily at weekly intervals
 Max: 60 mg daily in 2-3 divided doses
 Long-acting
› Starting dose based on clinical judgment
› Take once daily in the morning with a full glass of
water
› May increase dose weekly

17.  No known risk of abuse
 Indications
› refractory/intolerant to stimulants
› concerns about drug abuse
 For ages 6 and older
› Atomoxetine (Strattera)
› Clonidine (Kapvay)
› Guanfacine (Intuniv)

18.  Used off-label for ADHD
 Brand name: Wellbutrin
› Generic available
 MOA: inhibits reuptake of norepinephrine,
serotonin, and dopamine
 Dosing: 1.4-6 mg/kg/day in 1-3 doses

19.  ADR: tachycardia, headache, insomnia,
weight loss, dry mouth
 CI: seizure history, eating disorders
 Black box: suicidal ideation
 Caution in bipolar disorder
 Pregnancy Category C
 Renal/hepatic dosing

20.  Therapeutic alternatives to stimulants are
needed
› Some serious ADRs
› Tolerance can develop
› Drug abuse/dependence
› C-II medications are highly regulated; costs of lab
monitoring/office visits
*Bupropion affects the same NTs, may provide
another option for ADHD patients

22.  Objective: Compare the efficacy of
methylphenidate and bupropion in the
treatment of children/adolescents with ADHD
 Design: single-center, 6 week, randomized,
double-blind, parallel study

23.  Inclusion: ADHD-diagnosed, ages 6-17
 Exclusion
› Psychiatric comorbidities
› Suicidal ideation
› Mental retardation
› Epilepsy
› Drug abuse/dependence
› Hypertension/hypotension
› Cardiac issues

24.  Treatment arms
› Bupropion 100-150 mg/day (N=20)
› Methylphenidate 20-30 mg/day (N=20)
› Weight-based dosing; 3 doses/day
› Titrated over 3 weeks
 Primary outcome: Change in the score of the
parent-rated ADHD-RS-IV from baseline to
week 6

25.  Mean change in score from baseline
› Efficacy: p < 0.001 for both groups
› Treatment difference: -1.4
 p=0.554 (95% Confidence interval: -6.4 to 3.5)
 Statistics: RM ANOVA/independent t-test
› Inappropriate for ordinal data
 ADR: Methylphenidate & Headache;
adjusted p-value (Chi Square) was not
significant

26.  Wrong statistics used; no conclusions can be
made
 No placebo group
 Small sample size
 Medication adherence not assessed
 Ancillary medications not considered
 Short study duration

28.  Objective: Contrast the efficacy of
methylphenidate and bupropion in the treatment
of children/adolescents with ADHD
 Design: single-center, randomized, double-
blind, 12 week crossover study

29.  Inclusion
› ADHD-diagnosed, 7-17 years of age
› No ADHD medication for past 14 days
› Select psychiatric comorbidities allowed
 Exclusion
› Mental retardation (IQ < 70)
› Other psychiatric disorders
› Seizure history
› Eating disorders
› MAOI use

30.  Treatment arms
› Bupropion 50-200 mg/day (N=30)
› Methylphenidate 20-60 mg/day (N=30)
› Weight-based dosing; 2-3 doses/day
› Titrated over 3 weeks
 Primary outcome: Change in the parent and
teacher-rated Iowa-Conners Teacher’s Rating
Scale from baseline to week 6

31.  Mean change in score from baseline
› Efficacy: p < 0.001 for both groups
› Treatment difference: 3.1
 p > 0.05; confidence interval not provided
 Statistics: RM ANOVA/paired t-test
› Inappropriate for ordinal data
› ADR: no statistics reported

32.  Wrong statistics used
 No placebo group
 Small sample size
 Medication adherence not assessed
 Ancillary medications not considered
 Short study duration

33.  Methylphenidate remains the gold standard for
ADHD therapy
 Stimulants are first-line
› Use with caution if CV/BP issues
› Drug abuse/dependence  Daytrana patch,
Vyvanse
› Avoid other CNS stimulants (caffeine, ephedra)
› Extra costs: office visits/drug monitoring
› Monitoring: HR, BP, ECG/EKG prior to start,
psychiatric health

34.  When to consider bupropion?
› ADHD + depression
› No seizure history
› Drug abuse/dependence
› Refractory to FDA-approved drugs
 Avoid MAOI, tamoxifen, CNS depressants
 Monitor: HR, BP, ECG/EKG prior to start,
psychiatric health, renal/hepatic function

36. 1. Centers for Disease Control and Prevention Web site. ADHD
diagnosis and treatment. Accessed at
http://www.cdc.gov/ncbddd/ADHD/ on March 3, 2014.
2. American Academy of Pediatrics. ADHD: Clinical Practice
Guideline for the diagnosis, evaluation, and treatment of
attention-deficit/hyperactivity disorder in children and adolescents.
Accessed at
http://pediatrics.aappublications.org/content/early/2011/10/14/ped
s.2011-2654.full.pdf+html on March 1, 2014.
3. American Academy of Pediatrics. Implementing the key action
statements: an algorithm and explanation for process of care for
the evaluation, diagnosis, treatment, and monitoring of ADHD in
children and adolescents. Accessed at
http://pediatrics.aappublications.org/content/suppl/2011/10/11/ped
s.2011-2654.DC1/zpe611117822p.pdf on March 3, 2014.

37. 4. Consumer Reports Health. Evaluating Prescription Drugs Used to
Treat ADHD. Available at:
http://www.consumerreports.org/health/resources/pdf/best-buy-
drugs/ADHDFinal.pdf. Accessed March 1, 2014.
5. Clinical Pharmacology Web site. Available at:
http://clinicalpharmacology-ip.com.proxy.pba.edu/default.aspx.
Accessed March 1, 2014.
6. Lexicomp Online Web site. Available at:
http://online.lexi.com.proxy.pba.edu/lco/action/home/switch.
Accessed March 1, 2014.
7. Jafarinia M, Mohammadi MR, Modabbernia A, et al. Bupropion versus
methylphenidate in the treatment of children with attention-
deficit/hyperactivity disorder: randomized double-blind study. Hum
Psychopharmacol Clin Exp. 2012;27:411-418.
8. Barrickman LL, Perry PJ, Allen AJ, et al. Bupropion versus
methylphenidate in the treatment of attention-deficit hyperactivity
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