ADHD

Question 1

ADHD Epidemiology

Answer 1

• Affects 7.2% of children and adolescents worldwid
• Men twice as likely to be diagnosed
• Most have additional psychiatric diagnoses
• Men: conduct disorder, oppositional defiant disorder
• Women: anxiety and depressive disorders

Question 2

ADHD DSM Diagnosis Criteria

Answer 2

• < 17 y.o. with 6+ symptoms of hyperactivity/impulsivity OR inattention (can’t diagnose <4 y.o.)
• > = 17 y.o. requires 5+ symptoms of hyperactivity/impulsivity OR inattention
• Symptoms must persist at least 6 mo
• Present in multiple settings and interfere with academic or occupational functioning

Question 3

Inattention Symptoms

Answer 3

• Failure to give close attention to detail
• Difficulty sustaining attention in tasks
• Seemingly not listening when spoken to directly
• Not following through on instructions
• Difficulty organizing tasks
• Easily distracted by extraneous stimuli
• Avoidance of tasks requiring sustained mental effort
• Forgetful in daily activities

Question 4

Hyperactivity/Impulsivity Symptoms

Answer 4

• Fidgets with hands/feet or squirms in seat
• Leaves seat in situations when remaining seated is expected
• Runs about in inappropriate situations or appears restless
• Unable to engage in leisure activities quietly
• Talks excessively; answers prior to completion of questions
• Interrupts others; has difficulty waiting his/her turn

Question 5

Diagnosis Caveats

Answer 5

• Symptoms not due to defiance or lack of comprehension
• Several symptoms must be present before 12 y.o.
• Symptoms can be minimal or absent in certain settings
• Delays in motor, language, or social developments are common but not needed for diagnosis

Question 6

Stimulant Treatment Options

Answer 6

• Amphetamines

- Methylphenidate

Question 7

Non-Stimulant Treatment Options

Answer 7

• Atomoxetine
• Alpha-2 agonists
• Bupropion
• TCAs
• Polyunsaturated fatty acids
• Atypical antipsychotics (SGA)

Question 8

Amphetamine Pharmacology

Answer 8

• Multiple mechanisms promote concentration of monoamines in synaptic cleft
• Competition for reuptake through vesicular transporters
• Inhibition of VMAT-2 concentration monoamines in cytoplasm leading to exchange diffusion
• High dose will inhibit metabolism of monoamines by MAO
• Each amphetamine has different affinities for DA, NE, or 5HT

Question 9

Methylphenidate Pharmacology

Answer 9

• Binds to DA presynaptic transporter to inhibit DA reuptake from cleft
• Selectively increases DA only when it is actively released (“On Demand” effect)
• Slower uptake and clearance which is thought to lower its abuse potential

Question 10

Formulation Considerations

Answer 10

• Desired duration of effect
• Abuse potential
• Ease of administration
• Cost/formulary coverage
• Patient preference

Question 11

Atomoxetine

Answer 11

• Approved for ADHD in children, adolescents, and adults
• Increases NE and DA in prefrontal cortex like stimulants
• No effect in striatum (unlike stimulants) which lowers its abuse potential and slows its onset
• 0.5 mg/kg/day starting dose and titrate up
• BID dosing helps minimize GI AE

Question 12

Alpha-2 Agonists

Answer 12

• Activate alpha-2 receptors in prefrontal cortex and locus ceruleus
• Decreases NE-mediated arousal (hyperactivity) and increases blood flow to improve executive function and concentration
• Guanfacine ER and Clonidine ER approved for ADHD
• Used as monotherapy or with stimulants
• Clonidine is less selective and causes more sedation

Question 13

Bupropion

Answer 13

• Inhibits reuptake of NE and DA
• Milder effects than stimulants which lowers its abuse potential
• Faster onset than Atomoxetine and alpha-2 agonists
• SR or XL formulations and/or split dosing helps reduce SE
• No formulations are approved for ADHD

Question 14

TCAs

Answer 14

• Inhibits NE and 5HT reuptake with no appreciable effect on DA
• Desipramine is the most studied agent and only has off-label indication for ADHD
• CI in <12 y.o. due to sudden cardiac death
• Onset days to weeks
• Considered a third line after stimulants and atomoxetine
• Possible beneficial if tic disorder or Tourette’s also present

Question 15

Polyunsaturated Fatty Acids

Answer 15

• PUFA supplementation shown to have moderate effect on inattention symptoms
• May be more beneficial when combined with omega-3/6
• Also shown to improve overall treatment when combined with methylphenidate

Question 16

Antipsychotics

Answer 16

• Used for treatment-resistant aggression in ADHD
• Evidence limited to comorbid disruptive behavior disorders
• Significant risk for long-term adverse effects: weight gain, diabetes mellitus
• Reserve as absolute last-line therapy

Question 17

AE Pearls

Answer 17

• Insomnia: dose earlier and prescribe shorter acting formulation (atomoxetine may cause initial somnolence)
• GI upset/weight loss: administer with meals and try meal supplements
• Agitation/irritability/anxiety: reduce dose and slow titration
• Delayed growth: drug holidays
• HTN/tachycardia: use lower dose, add alpha-2 agonist, minimize secondary contributors

Question 18

Screening

Answer 18

• PCP should screen and consult specialist as needed
• Use DSM-based criteria for diagnosis
• Screen for potential comorbidities

Question 19

Age Groups + Recommendations

Answer 19

• 4-5 y.o.: try behavioral therapy first and then methylphenidate if necessary
• 6-11 y.o.: use medication and/or behavioral therapy, stimulant medications have strongest evidence
• 12-18 y.o.: use medication first line, assess for comorbid substance abuse

Titrate medications to maximize benefits and minimize AE

Question 20

Texas ADHD Algorithm

Answer 20

Stage 0: Non-medication options
Stage 1: MPH or AMP
Stage 2: Agent not used in stage 1
Stage 3: Atomoxetine
Stage 4: Bupropion or TCA
Stage 5: Agent not used in stage 4
Stage 6: α2-agonist