Term
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Definition
• Most prevalent neurodevelopmental disorder in children
- ~ 10% of all U.S. children diagnosed with ADHD
- 50–60% of child cases persist into adulthood • Average age of diagnosis: 7 years
• Lower educational and occupational performance, attainment, attendance |
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Term
| Etiology and Risk Factors for ADD/ADHD |
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Definition
- Genetics
• 70–80%heritability
- Male gender
• M:F ratio: 3–4:1
- Environmental
• Leadexposure
• Alcohol/drug/smoking exposure in utero
- Neurobiology
• Impaired functioning of prefrontal cortex/ anterior cingulate cortex
• Deficits in ventral striatal areas
- Low birth weight/prematurity
- Nutritional deficiencies |
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Term
| DSM 5 Diagnostic Criteria for ADD/ADHD |
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Definition
A.
A persistent pattern of inattention AND/OR
hyperactivity-impulsivity that interferes with functioning or development, as characterized by:
1. Inattention: >6 of the following x > 6 months:
• Fails to give close attention to details/makes careless
mistakes
• Difficulty sustaining attention
• Does not seem to listen
• Does not follow through with instructions and fails to finish work
• Difficulty organizing tasks and activities
• Avoids/dislikes tasks that require sustained mental effort
• Loses things
• Easily distracted
• Forgetful in daily activities
2. Hyperactivity and impulsivity: >6 of the following x >
6 months:
• Fidgets or taps hands/feet, squirms in seat
• Leaves seat often
• Runs around/climbs in inappropriate situations
• Unable to engage in leisure activity quietly
• “On the go” or acting as if “driven by a motor”
• Talks excessively
• Blurts out answers
• Difficulty waiting turn
• Interrupts others
• Several symptoms must be present before age 12
• Present in > two settings
• Interfere with function
• Not better accounted for by another mental disorder |
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Term
| Common Comorbid Conditions for ADD/ADHD |
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Definition
• Learning and language disorders
• Conduct disorder/oppositional defiant disorder
• Tic disorders
• Autism spectrum disorders
• Bipolar disorder
• Substance use disorder |
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Term
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Definition
| impulsivity, hyperactivity, inattention |
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Term
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Definition
nonpharmacologic:
• Diet
• Social skills training
• Cognitive behavioral therapy
• School-based interventions
pharmacologic:
• Stimulants
• Non-stimulants |
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Term
| Behavioral interventions: for ADHD |
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Definition
- Parent training, school interventions: • Most effective for preschool age
• Adjunct in children and adolescents
• Often inferior to medications for core symptoms of ADHD |
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Term
| Diet and dietary supplements: for ADHD |
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Definition
• Omega-3 fatty acids: Adjunct to pharmacologic
treatmentàminimal side effects, mixed efficacy results in trials
• Iron supplementation if iron deficient
• No evidence of benefit: Vitamin C, vitamin E, St. John’s Wort
• No evidence that sugar or aspartame avoidance improves ADHD symptoms |
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Term
| Methylphenidate (Ritalin®) is what type of medication |
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Definition
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Term
| Multimodal ADHD Treatment Study |
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Definition
• NIMH funded 14-month trial of ADHD treatment (1999)
• Four treatment groups:
1. Methylphenidate
• Titration followed by monthly visits
2. Intensive behavioral therapy (IBT)
• Parent, school, child components
3. Combination of methylphenidate and behavioral therapy
4. Community-based care (control group)
• Included 579 children ages 7–9 years old at trial entry
• 19 primary outcome measures
- Results:
• Reduction in symptoms in all groups
• Medication and combination treatment significantly more effective than IBT or community care alone
• Medication was superior to IBT for reducing core symptoms of ADHD
• Combination therapy resulted in greater improvements in anxiety symptoms, parent-child relationships, social skills, and academic performance • Required lower doses of medications |
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Term
| Preschool ADHD Treatment Study |
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Definition
•NIMH funded (2006)
Included 165 children ages 3.5–5 years old at trial entry
Randomized to IR methylphenidate or placebo
Results:
• Methylphenidate more effective than placebo at achieving
“excellent” response (2.5-, 5-, 7.5-mg TID)
• Less tolerable in preschool-age children • Higher dropout and adverse effect rates than children > 6 years
• Large treatment response rate (75%) in patients with ≤ 1
comorbid condition |
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Term
| American Academy of Child and Adolescent Psychiatry (2007) treatment guidelines for ADD/ADHD |
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Definition
• No age stratification
• Published prior to alpha agonists obtaining FDA approval
• First line: Stimulants or atomoxetine
• Second line: Behavioral therapy or alpha agonists, bupropion, tricyclic
antidepressants (TCAs) |
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Term
| American Academy of Pediatrics (2011) treatment guidelies for ADD/ADHD |
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Definition
• Recommendations based on age
• Preschoolers < 5 years old:
First line: Behavioral therapy
- Second line: Medication (stimulant)
• Children and adolescents (6–18 years old):
- First line: Medication (any FDA-approved med, but stimulants preferable) ± behavioral therapy |
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Term
| ADD/ADHD medication therapy |
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Definition
1st line: • Stimulants (effect size ~ 0.9
2nd line:
• Atomoxetine (Strattera®) (effect size ~ 0.6)
• Guanfacine (Intuniv®) (effect size ~ 0.5)
• Clonidine (Kapvay®) (effect size ~ 0.5)
3rd line:
• Bupropion (Wellbutrin®)
• Modafinil (Provigil®) |
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Term
| Treatment Take-Aways for ADHD |
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Definition
- Core symptoms are better treated with medication
- Behavioral/psychosocial interventions help with:
• Long-term management of ADHD
• Treatment of comorbidities
• Self-esteem
• Social skills
• Peer/family relationships |
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Term
National Survey of Children With
Special Health Care Needs |
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Definition
• Parent survey 2009–2010
• Children aged 4–17 years
• Findings
• < 33% of children > 6 years old received preferred treatment (combination)
• 50% of preschoolers received behavioral
treatment (1st line for this age group) |
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Term
| Common Adverse Effects of stumulants |
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Definition
• Decreased appetite • Weight loss
• Headache
• Insomnia
• Abdominal pain
• Dizziness
• Nervousness
• Emotional lability
• Dry mouth |
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Term
| Risks Associated with Excessive Use of stimulants |
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Definition
• Cardiovascular failure
• Irregular heartbeat
• Hypertension
• Paranoia
*Risk increases significantly when used IV or intranasally |
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Term
| Methylphenidate vs Amphetamines |
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Definition
Methylphenidate
• FDA approved since 1955
• Approved for use in children > 6 years old (patch 6–12)
Amphetamines
•Dextroamphetamine and
mixed amphetamine salts FDA approved in late
1990s
-Approved for use in children > 3 years old (IR) and > 6 years old (XR) |
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Term
| has MOA blockade of dopamine transporters (minimal effects on norepinephrine) |
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Definition
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Term
has MOA Stimulate release of dopamine, norepinephrine
(and serotonin at higher doses) |
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Definition
| Amphetamines, Dextroamphetamine and mixed amphetamine salts |
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Term
| short-acting methylphenidate agents |
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Definition
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Term
| intermediate-acting methylphenidate agents |
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Definition
Ritalin SR®
Metadate ER®
Methylin ER® |
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Term
| long-acting methylphenidate agents |
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Definition
Metadate CD®
Ritalin LA®
Concerta®
Daytrana®
Quillivant XR®
Quillichew ER®
Aptensio XR® |
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Term
| Dexmethylphenidate agents |
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Definition
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Term
| advantages of Immediate Release Methylphenidate |
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Definition
• Allows for flexible dosing
• Can be split or crushed
• Can be added to long- acting formulation for
additional afternoon coverage
• Simple to discontinue
• Available generically
• Reduces severity of adverse effects
• Reduced abuse potential
• Can be administered once daily (but may require BID dosing) |
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Term
| disadvantages of Immediate Release Methylphenidate |
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Definition
• Short half-life(~2.5hrs)
• Does not cover ADHD symptoms throughout school day
• Requires 2–3 times daily dosing
• Tablets must be swallowed whole
• Delayed peak (full symptom control may not
occur until afternoon) |
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Term
• 12-hour duration
• Tablet shell eliminated in stool
• Can be taken with or without food
• Cannot crush or chew (less likely to be snorted)
• Late release may cause insomnia |
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Definition
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Term
• 50/50 mixture of delayed release and IR beads • Contents can be sprinkled on applesauce
• Release is pH dependent (avoid antacids/acid suppressants) • Time to first peak quicker than Concerta® |
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Definition
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Term
• 70/30 mixture of extended-release and IR beads • Should be taken in the morning before breakfast
• Contents can be sprinkled on applesauce
• Approximately 7-hour duration to cover school day |
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Definition
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Term
• 60/40 mixture of extended-release and IR beads • 12-hour duration
• Contents can be sprinkled on applesauce |
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Definition
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Term
• Extended release oral liquid
• 80/20 mixture of extended-release and IR components
• Oral suspension does not require refrigeration • Stable for four months after reconstitution
• 12-hour duration |
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Definition
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Term
• Long-acting chewable
• 70/30 mixture of extended-release and IR components
• 8-hour duration |
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Definition
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Term
• Transdermal patch
• Not bioequivalent with oral dosage forms
• Patch can be removed any time to customize stimulant exposure • 2-hour delay in effect after application
• Wear no longer than nine hours per day • Apply to hip, do not cut patches
• May have more insomnia, anorexia, and tics than oral forms |
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Definition
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Term
• D-threo enantiomer of racemic methylphenidate
• Dose is half of typical methylphenidate doses
• Available in IR (Focalin® ) and extended-release
(Focalin XR®) formulations
• FocalinXR® release is pH dependent: avoid antacids, proton pump inhibitors, and H2 blockers
• FocalinXR® caps can be opened, sprinkled on applesauce |
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Definition
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Term
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Definition
| Adzenys XR, Dyanavel, Evekeo |
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Term
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Definition
| Dexedrine, Dexedrine Spansule |
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Term
| Mixed Amphetamine Salts agents |
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Definition
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Term
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Definition
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Term
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Definition
| amphetamines, dextroamphetamine, mixed amphetamine salts, lisdexamfetamine |
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Term
| Amphetamine clinical pearls |
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Definition
• Adzenys XR: first ODT, 50/50 delayed-release and IR particles (similar PK to Adderall XR)
• Dynavel XR: oral suspension, mixture of IR and ER particles
• Vitamin C/fruit juice decreases amphetamine absorption
• Sodium bicarbonate increases absorption |
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Term
| Dextroamphetamine (IR and SR) clinical pearls |
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Definition
| • IR:Forage>3years;SR:>6years • IR available in liquid |
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Term
| Mixed amphetamine salts (IR and ER) clinical pearls |
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Definition
• Decreased sense of fatigue, mild euphoria, increased motor activity
• IR:Forage>3years;SR:>6years
• IR can be crushed; ER can be opened and put in
applesauce
• ER: 50:50 mix of IR and ER beads |
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Term
| Lisdexamfetamine clinical pearls |
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Definition
• Oral prodrug converted to dextroamphetamine
• Transformation to active drug in gut prevents
snorting/injecting
• Longest duration of action of amphetamines
• Amphetamine uptake slower: less euphoric effects
• Capsule can be opened and dissolved in water |
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Term
| Atomoxetine (Strattera®) MOA |
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Definition
| Selective norepinephrine reuptake inhibitor |
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Term
• Less effective than stimulants
• Slower onset of effect (1–4 weeks)
• Longer treatment duration increases probability of response
• Generic became available recently (2017) |
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Definition
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Term
has S/E:• Nausea/vomiting, abdominal pain
• Weight loss, ↓ appetite
• Tachycardia
• Headache
• Insomnia
• Hepatotoxicity
• Myocardial infarction
• Priapism |
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Definition
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Term
Reasonable option for the following populations:
• Patient does not respond to or tolerate stimulants
• Families who want to avoid controlled substances
• Patients or families with history of substance abuse |
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Definition
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Term
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Definition
| Guanfacine ER, clonidine ER |
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Term
| Guanfacine ER, clonidine ER MOA |
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Definition
Inhibit presynaptic norepinephrine release and increase blood flow to
prefrontal cortex (alpha-2 agonists) |
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Term
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Definition
• Longer half-life and duration of action for guanfacine (18 hrs) compared to clonidine (12 hrs)
• Less sedation and dizziness with guanfacine |
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Term
• Not as effective as stimulants for monotherapy
• May be used to reduce disruptive behavior, control aggression, insomnia, tics |
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Definition
| Guanfacine ER, clonidine ER. Alpha-2 Agonists |
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Term
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Definition
| Dopamine reuptake inhibitor |
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Term
| Has ADE: nausea/vomiting, rash, seizure |
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Definition
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Term
• Delayed onset:~two weeks
• No abuse potential, good for comorbid depression |
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Definition
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Term
• Wake-promoting stimulant
• Effective in treatment of ADHDsymptoms
• Not approvable letter from FDA due to skin reactions (including Stevens Johnson Syndrome) |
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Definition
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Term
| Cardiovascular ADE of stimulants |
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Definition
cause minor increases in systolic/diastolic blood pressure and heart rate
- Frequency of sudden death in stimulant-treated children is the same as for the general population
- Recent cohort study showed CV events rare, but twice as likely in stimulant users than non-users
• Alpha-2 agonists cause a symptomatic decreases in blood pressure and heart rate
• AAP,AHA, and AACAP all recommend thorough history and physical exam to detect cardiac disease prior to starting medication (EKG optional) |
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Term
| Appetite and growth ADE of stimulants |
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Definition
• Loss of appetite common with stimulants, less with atomoxetine
• Height attenuation with stimulants is dose dependent
• Estimated to be approximately 1 cm/year for up to three years of use
• Height/weight/BMI measurements recommended 1–2 times/year
• If growth significantly impacted, consider drug holidays or change of agent |
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Term
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Definition
• Stimulants
• Insomnia from extended medication effects
vs. rebound of ADHD symptoms when meds wear off
• Atomoxetine and alpha-2 agonists usually sedating
• Evaluate sleep quality and type of disturbance
• Change stimulant formulation
• Change medication
• Rule out comorbid sleep apnea or restless legs
• Add sleep agent |
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Term
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Definition
• Stimulants unlikely to cause new-onset tics
• Stimulants may exacerbate pre-existing tics
• Consider atomoxetine or alpha-2 agonists with comorbid tic disorders |
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Term
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Definition
• Substance use/abuse more common in adolescents with ADHD than age-matched peers
• No evidence that stimulants increase risk of developing substance use disorder
• Screen for patients at higher risk for diversion or abuse
• Consider medications with lower abuse potential in patients with personal or family histories of substance use disorders |
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Term
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Definition
• Very low risk of mood disturbances, psychosis, or mania
• Black box warning about suicidal ideation in atomoxetine labeling |
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Term
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Definition
• 2–3 times more likely in children with ADHD compared to age-matched peers
• No evidence that treatment with ADHD medications increases risk |
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Term
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Definition
| • Rarely reported with atomoxetine and methylphenidate |
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Term
| adverse effects have been associated with stimulant treatment? |
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Definition
| Appetite suppression, tachycardia, tics |
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Term
| Treatment Goals and Expectations for ADD/ADHD |
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Definition
• Alleviate core symptoms of inattention, impulsivity, and hyperactivity
• Improve functioning at home and school
• Improve academic performance
• Improve social skills
• Decrease classroom disruptions |
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Term
| Treatment Considerations for ADD/ADHD |
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Definition
• Family wishes
• Past trials
• Anticipated adverse effects
• Available dosage forms
• Comorbid conditions
• Personal/family history of substance abuse
• Cost |
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Term
ADHD and Conduct Disorder/Oppositional Defiant
Disorder management |
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Definition
• Stimulants have anti-aggressive effects • 2nd line: Behavioral therapy followed by
antipsychotics/VPA/Lithium |
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Term
| ADHD and Bipolar Disorder management |
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Definition
| • Treat bipolar 1st with mood stabilizer • If ADHD sxs continue, add stimulant |
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Term
| ADHD and Major Depressive Disorder management |
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Definition
• Treat most disabling condition first
• Depression: CBT, SSRIs, venlafaxine |
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Term
| ADHD and anxiety disorders treatment |
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Definition
• CBT before or with ADHD treatment
• Consider stimulant or atomoxetine
• Add SSRI if symptoms continue |
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Term
| ADHD and Tic disorders treatment |
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Definition
• Consider methylphenidate or atomoxetine
• Alpha agonists can improve tics and ADHD sxs |
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Term
| ADHD and substance use disorders treatment |
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Definition
• 1st: Treat active substance abuse • Can treat both concomitantly
• Use stimulant with low abuse potential or consider non-stimulant |
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Term
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Definition
• Methylphenidate and amphetamines inhibit monoamine
oxidaseàavoid MAOIs
• Methylphenidate can increase blood levels of tricyclic
antidepressants
• CYP2D6 inhibitors increase levels of amphetamine and
atomoxetine
• Combination of stimulants and serotonergic agents (antidepressants/tramadol) may increase seizure or
serotonin syndrome risk
• Use caution co-administering alpha agonists with other
blood pressure lowering medications |
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