Lecture 64 - Pharmacotherapy of ADHD Flashcards
Overview of ADHD
higher rate is diagnosed in a first -degree relative
etiology is multifactorial (environmental, genetics, physiological)
Clinical Course
one-third of children with ADHD will have the diagnosis in adulthood
increased risk of substance use and antisocial personality disorder if ADHD is left untreated
Potential impact of ADHD
Poor academic performance
Low self-esteem
Poor interpersonal relationships
Employment difficulties
ADHD Diagnostic Criteria
For each symptom domain, must have at least 6 symptoms present
For older adolescents and adults (17 years and older), at least 5 symptoms are required for either of the two specifiers
Several inattentive or hyperactive symptoms must be present prior to age 12 years
Several inattentive or hyperactive-impulsive symptoms are present in two or more settings
ADHD Types
Combined: criteria met for both inattention and hyperactivity
Predominantly inattentive presentation: criteria met for inattention, but not hyperactivity
Predominantly hyperactive/impulsive presentation: criteria met for hyperactivity/impulsivity but not inattention
Inattention
Six or more of the following symptoms persisting for at least 6 months; inconsistent with developmental level and negatively impacting daily functioning: Fails to give close attention to details, makes careless mistakes; Difficulty sustaining attention in tasks or play activities; Doesn’t seem to listen when spoken to directly; Doesn’t follow through on instructions, fails to finish homework, chores, duties in the workplace; Difficulty organizing tasks and activities; Avoids, dislikes, reluctant to engage in tasks that require sustained mental effort; Loses things necessary for tasks/activities; Easily distracted by extraneous stimuli; Forgetful in daily activities
Hyperactivity and Impulsivity
Six or more of the following symptoms persisting for at least 6 months inconsistent with developmental level and negatively impacts functioning: Fidgets with or taps hands/feet, squirms in seat; Leaves seat in situations when remaining seated is expected; Runs about or climbs in inappropriate situations; Unable to play or engage in leisure activities quietly; “On the go”, acting as if “driven by a motor”; Talks excessively; Blurts out an answer before a question is completed; Difficulty waiting their turn; Interrupts or intrudes on others
Non-Pharmacologic Treatment Options
Behavioral therapy and psychosocial treatment; training interventions
Pharmacologic Treatment Options
stimulants (amphetamine or methylphenidate-based)
non-stimulants
Stimulant Dosing
Dose-response effects seen in a short period of time
Calculating a dose in pediatric patients based
on mg/kg not found to be helpful as variations in dosing not found to be due to height or weight
IR preferred for patients weighing < 16 kg due to limited low-dose availability of long- acting stimulants
Avoid giving dose too late in the day, may give an after-school dose
Late afternoon symptoms may require longer-
acting formulation
Don’t use two different stimulants, Can use two different dosage forms of the same stimulant
Special Considerations - Mydayis
mixed amphetamine salts
only for ages 13-17
Special Considerations - Daytrana
methylphenidate
only patch formulation
Special Considerations - Vyvanse
lisdexamfetamine
prodrug covalently linked to l-lysine; converted to dextroamphetamine via first-pass metabolism/hepatic metabolism
NOT useful if no response to dextroamphetamine
Special Considerations - Jornay PM
methylphenidate hydrochloride
take dose in evening between 6:30 and 9:30 pm
Stimulant adverse effects
Appetite loss
Abdominal pain
Headaches
Sleep disturbances
Decreased growth (1 to 2 cm, diminished after 3rd year of treatment)
Hallucinations or other psychotic symptoms (rare)
Increased blood pressure (1 to 4 mmHg) Increased heart rate (1 to 2 bpm)
Sudden cardiac death (rare)
Priapism
Peripheral vasculopathy (Raynaud’s)
Stimulants: Common Adverse Effects and Management - reduced appetite, weight loss
High-calorie meal when stimulant effects are low (breakfast, dinner)
Stimulants: Common Adverse Effects and Management - stomach ache
Give on full stomach, lower dose if possible
Stimulants: Common Adverse Effects and Management - insomnia
dose earlier in day, lower last dose of day or give earlier, consider sedating med at bedtime
Stimulants: Common Adverse Effects and Management - headache
Divide dose, give with food, give analgesic
Stimulants: Common Adverse Effects and Management - rebound symptoms
Longer-acting stimulant trial, atomoxetine, antidepressant
Stimulants: Common Adverse Effects and Management - Irritability, jitteriness
Assess for co-morbid condition, reduce dose, consider mood stabilizer or atypical antipsychotic
Stimulants: Uncommon Adverse Effects and Management - hallucinations
d/c stimulant, reassess diagnosis
Stimulants: Uncommon Adverse Effects and Management - risk for suddent cardiac death
Risk no greater in clinical trials than general population – assess risk of cardiac structural abnormality and family history – if concern, cardiac ECHO
Stimulant Monitoring
appetite, behavior, blood pressure, growth rate (height/weight), heart rate, sleep, ECG may be considered based on cardiac risk
Alpha 2 Agonists
Guanfacine ER: 3A4 substrate
Clonidine ER
must be tapered if discontinued to avoid rebound HTN
Norepinephrine Reuptake Inhibitors
Atomoxetine: 2D6 substrate; weight-based dosing for those less than 70 kg
Viloxazine: capsules - swallow whole or put in applesauce; 2D6/UGT substrate, strong 1A2 inhibitor
Non-Stimulant Adverse Effects - atomoxetine and viloxazine
increased HR and BP, increase in suicidal thinking (boxed warning)
Non-Stimulant Adverse Effects - clonidine and guanfacine
- Decreased HR and BP, orthostasis
- Somnolence
- Dizziness
- Rebound hypertension if abrupt discontinuation
Monitoring for Non-Stimulants
Appetite
Behavior
Blood pressure
Growth rate (height and weight) (atomoxetine) Heart rate
LFTs (atomoxetine)
Sleep
Bupropion
Not FDA-approved for ADHD
2D6 inhibitor
Contraindicated in seizure disorders and eating disorders
Tricyclic Antidepressants
Less effective than methylphenidate
Cardiac concerns – sudden cardiac death in children, lethal in overdose
Mood Stabilizers: Atypical Antipsychotics
May be useful if there is comorbid bipolar disorder, conduct disorder, intermittent explosive disorder
Should not use atypical antipsychotics as monotherapy!!!
American Academy of Pediatrics (AAP) ADHD 2019 Treatment Guidelines
preschool age:
* First-line: parent training in behavior management (PTBM)
* Second-line: PTBM plus FDA-approved medication
elementary and middle-school age:
* First-line: FDA-approved medication plus PTBM
adolescents (age12-18):
* First-line: FDA-approved medication, may offer PTBM
AAP Medication Recommendations - preschool age
- First-line: Methylphenidate
AAP Medication Recommendations - Elementary/Middle School/Adolescents
- First-line: Stimulants
- Second-line: Atomoxetine, Guanfacine ER, Clonidine ER
AAP Medication Recommendations - Adjunctive Treatment
- Only guanfacine ER and clonidine ER have evidence as adjuncts to stimulants
NICE: ADHD Guidelines 2018 for Adults
Methylphenidate (short- or long-acting) OR Lisdexamfetamine (if no response to one, switch to the other)
Dextroamphetamine (If unable to tolerate lisdexamfetamine long half-life)
Atomoxetine (if no symptom response to above agents)
