ADHD and Enuresis Flashcards
DSM-V (Diagnostic and Statistical Manual of Mental
Disorders, 5th edition) diagnostic criteria
Persistent pattern across settings of inattention,
hyperactivity, or impulsivity
Validated screening tools - ADHD
Children: Vanderbilt® Connor©
• Adults: World Health Organization Adult ADHD SelfReport Scale and the Diagnostic Interview for ADHD in
adults (DIVA 2.0)
Neurobiology of ADHD
- Complex; has genetic and environmental factors
- Genetic
- Heritability 60% to 90%
- 28% of ADHD cases accounted for by genetics
- Environmental factors
- Low birth weight and prenatal complications
- Malnutrition
Evidence-Based Treatment of ADHD
• Two sets of guidelines
American Academy of Pediatrics (AAP)
• American Association of Child and Adolescent Psychiatrists (AACAP)
AAP Guidenlines
Behavioral therapy first line for children 5 years of age or younger
• Stimulants first-line therapy
AACP guidelines
Stimulants first line therapy for children 6 years of age or older
ADHD (cont.)
• Goals of Pharmacotherapy
Modulate Dopamine (DA) and Norepinephrine (NE) to improve executive function
and regulate arousal to improve performance (Dipiro p. 1145)
• *multimodal therapy most successful
• * remember ADHD often coexists with other mood and behavior disorders which
increases the challenge of prescribing pharmacotherapy\
ADHD Options
Options • Stimulants • Methylphenidate • Amphetamines • Non-Stimulants • SNRI • Alpha-Agonist
Stimulants Methylphenidate - MOA
Absorption: readily absorbed Distribution: variable by age Protein-Binding: variable; low Metabolism: Liver Elimination: Renal
Stimulants Methylphenidate - PK/PD
Onset 1h. Peak 3-11h (depends on formulation). ½ life: 2-4h
Stimulants Methylphenidate - + Effects
Low doses: reduce movement, impulsivity, and increase cognitive function including sustained attention and working
memory
Stimulants Methylphenidate - Neg Effects
higher doses: impaired cognition and locomotor-activating effects.
Black Box Warning: abuse potential
LT use: growth suppression
CV risk: sudden death
Psych risk: increases Tics in comorbid tic condition
Appetite suppression, tachycardia, dizziness, headache (HA), insomnia, growth suppression
Stimulants Methylphenidate - Monitoring
Screen for CVD: congenital, arrhythmia, other disease; MH: psychosis, bipolar, aggression; Neuro: Seizures, Vision disturbance, GI
Labs: CBC with differential, Platelets (maybe); Growth parameters
Stimulants Methylphenidate Interactions
ncreases serum concentrations of: TCAs, SSRIs, phenylbutazone, warfarin, phenytoin, phenobarbital, and primidone
Caution: clonidine, anticonvulsants, antihypertensives. Contraindicated: MAOI
Pregnancy: risk vs. benefit: lower weight NB; old category C
Stimulants Amphetamines - MOA
Elevates extracellular dopamine (DA) and prolongs DA receptor signaling in the striatum
Inhibits the reuptake of monoamine oxidase which acts synergistically to produce a significant increase in the
monoamine concentration
Weak dopamine reuptake inhibitor, moderate noradrenaline reuptake inhibitor and very weak serotonin reuptake
inhibitor.
Stimulants Amphetamines - PK/PD
Absorption: Well absorbed Distribution: high volume Protein-binding: low Metabolism: Liver CYP2D6 Elimination: renal
Stimulants Amphetamines - Action
Peak 1-3h (o) 15” Inject. ½ life: varies, 9-14h
Stimulants Amphetamines - POS Effects
Improve the core symptoms of ADHD in the short term
Gains in social and classroom behaviors
Stimulants Amphetamines - NEG Effects
Black Box warning: abuse potential
Linked to a higher risk of experiencing adverse events such as sleep problems, decreased appetite, and stomach pain
Appetite suppression, tachycardia, dizziness, headache (HA), insomnia, growth suppression, masks exercise fatigue
Stimulants Amphetamines - Monitoring
Screen for CVD: congenital, arrhythmia, other disease; MH: psychosis, bipolar, aggression; Neuro: Seizures,
Vision disturbance, GI
Labs: CBC with differential, Platelets (maybe); Growth parameters
Stimulants Amphetamines - Interactions
MAOIs AND those listed under Methylphenidate
Long-acting stimulant medications are generally preferred for
school-age children
Start with a 1st line medication from the methylphenidate or dextroamphetamine-amphetamine class, depending
on patient’s age. - 1st, 2nd, and 3rd line examples
1
st Line: Methylphenidate (Ritalin LA, Metadate CD; dextroamphetamine/amphetamine, LA: Adderall XL
• 2
nd Line: Methylphenidate, LA: Concerta; Dexmethylphenidate, LA: Focalin XR
• 3
rd Line: Lisdexamfetamine, LA: Vyvanse
Maximize dosing of one agent before
moving to the next. If ineffective or side effects develop, switch classes,
then move to second line medication if needed.
Before considering a stimulant medication, obtain
cardiac history, including sudden cardiac death in first degree
relative under age 50, history of congenital heart defect, or conduction defect.
• Maximize dosing of long-acting
stimulant before adding an immediate release formulation medication
Insufficient evidence exists for switching
methylphenidate to amphetamines. Consider switching from methylphenidate to amphetamines at
half of the dose.
When switching dexmethylphenidate to methylphenidate, the methylphenidate dose should be
twice the dexmethylphenidate dose.
Concerta® (methylphenidate ER) and Vyvanse® (lisdexamfetamine) are uniquely
dosed. The table below provides an initial dose which
may require additional titration.
Non-Stimulants: Atomoxetine - MOA
Selective inhibitor of Norepinephrinereuptake; Increases the amount of norepinephrine in the brain
Non-Stimulants: Atomoxetine - Action
Plasma levels peak within 1-3h; 6 weeks before it reaches maximum effect
Non-Stimulants: Atomoxetine Pos effects
No abuse potential; not a schedule II
Works around the clock
Useful inpatients with comorbid anxiety
Non-Stimulants: Atomoxetine Neg Effects
2/3 as effective as stimulants
Black Box Warning: May increase suicidal thoughts at initiation
GI effects: decreased appetite, upset stomach, nausea or vomiting, jaundice; GEN: tiredness, problems sleeping; CV: CV
events; NEURO: dizziness; Mental Health: negative.
Non-Stimulants: Atomoxetine Monitoring
CVD and health, Growth parameters, Mental health, GI status, LFTs; MH status
Non-Stimulants: Atomoxetine Interactions
Lower doses if patient on SSRIs: paroxetine or fluoxetine. Avoid: CYP2D6 inhibitors
Contraindicated: MAOIs, glaucoma, Pheochromocytoma
Pregnancy: Risk versus benefit
Guanfacine LA
• Used to treat
children with ADHD who have tics, sleep problems, and/or
aggression
Guanfacine LA activates
Activates presynaptic alpha2
-adrenergic receptors in the brain
Guanfacine LA does not
Does not cause much appetite suppression
Guanfacine LA may cuase
May cause sleepiness, headaches, fatigue, stomachaches, nausea, lethargy,
dizziness, irritability, decreased blood pressure, and decreased appetite
Guanfacine LA takes up to
Takes up to 3-4 weeks to see effect
Long-Acting Clonidine (Kapvay) FDA approved
• Principal side effects
Somnolence, fatigue, and hypotension
Enuresis DX
Diagnosis: voiding history/pattern, consider age, rule out physical
Enuresis Epidemiology
Epidemiology • 4 years:25% of children • 7 years, only 5-10% • 10 years, fewer than 5% of children • Spontaneous resolution rate = 15% per year
Enuresis Treatment
Nonpharm first
• Lifestyle, behavioral modification, reassurance, education, wet alarm
• Medication consideration
• Over age 7 years
• No improvement after 3 months of other therapies
• Can be used intermittently for special occasions
Desmopressin Oral or disintegrating tablet
- 1 hour before bed
- 0.2 mg initiall, titrate as necessary to a maximum dose of 0.6 mg
- Reduces bedwetting 1.3 fewer nights/wk
- Serious SE: water intoxication; counsel on fluid restriction when taking
Anticholinergic (oxybutynin 2.5-5 mg at HS, tolteridine>12 y)
• Indications: dysfunctional voiding, overactive bladder, neurogenic bladder
• MOA: Reduce uninhibited detrusor contractions, increase the threshold volume at
which an uninhibited detrusor contraction occurs, and enlarge the functional bladder
capacity
• Anticholinergic SE: dry mouth, constipation
• Useful in some if daytime wetting
• Can be combined with desmopressin
Imipramine (TCA)
- Dose at HS: 25 mg for patients aged 6-8 years and 50-75 mg older children
- One fewer wet night per week
- High relapse rate
- SE profile: WHO no longer recommends
