# Presentation: 290386

## FDA Pediatric Advisory Committee

- June 30, 2005
- Marsha D. Rappley, MD

## Managing Children and Adolescents with ADHD in Primary Care

- Source of referrals
- Issues in diagnosis
- Treatment options
********Medications in treatment of ADHD********
- Choice of medication
- Establishing an effective dose
- Monitoring for effectiveness and side effects

## Source of referrals

- Most children and adolescents with ADHD are managed in primary care
- ADHD is one of the most common reasons for an office visit for school aged children
- Stimulant medications are among the 10 most frequently prescribed medications for children
- Referrals
- Self referrals from the primary care practice
- Referrals from schools
- Referrals to pediatrics from family practice

## Diagnostic issues

- Guidelines
- American Academy of Pediatrics
- Adopted by American Academy of Family Physicians
- American Academy of Child and Adolescent Psychiatry
- European groups as well

## Common to these guidelines

- Comprehensive history
- Information from important domains of the child’s life
- More than one source
- Typically parents, school and child or teen
- Use of standardized checklists
- Allows comparisons of behavior to children of same age
- Asses for co-existing conditions

## Common to these guidelines

- ADHD as chronic health condition
- Establishment of treatment goals
- Medication with stimulants to manage symptoms
- Behavior therapy for parent-child conflict, oppositional behavior; psychological therapy for co-existing conditions
- Taken together, these guidelines establish a standard of care

## Considering treatmentfor ADHD

- Inattention: Medication
- Methylphenidate
- Dextroamphetamine products (including mixed salts)
- Atomoxetine
- Bupropion
- Hyperactivity and Impulsivity: Medication
- Oppositional behavior: Med + Counseling
- Parent child conflict: Med + Counseling

## Considering medications

- Stimulants first line
- Most effective: 68-80%
- 3-4% experience side effects causing discontinuation of medications
- Provide targeted coverage
- Available as generic
- Products with duration
- 2 -4 hr, 4 – 8 hr, 8 – 12 hr

## Considering medications

**Atomoxetine** second line
- Effective 50 – 60%
- Similar side effects to stimulants
- Provides 24 hour coverage
- 1-3 weeks to reach effect
**Bupropion**
- Fewer studies, more serious side effects
- Role of antidepressant effect
- 24 hour coverage with twice daily dosing
- 3-4 weeks to reach effect

## Choosing a medication

- Stimulant usually chosen for most children and teens
- MPH and DEX have similar profiles
- DEX slightly more side effects, which are mild
- Mixed salt preparation (Adderall®)
- Recent withdrawal of long acting product in Canada
- Warning of use in children with cardiac conditions
- Parent may have preference

## Setting target outcomes

- Measurable desired outcomes are preferred
- Inattention
- Work completion, time on homework, spelling tests, timed math tests, fluidity of thinking and writing (copying from the board, note taking)
- Hyperactivity and impulsivity
- Calls from school, episodes of detention, participation in activities without disruption (cub scouts, sports)

## Setting target outcomes

- Quality of relationships
**Peers**: teasing, friendship, time in play
**Teachers**: decreasing negative, increasing positive interactions, engagement in learning activities
- Parents: decreasing negative, increasing positive interactions, time for affection and support
**Siblings**: decreasing negative, increasing positive interactions, decreasing reactivity,

## Setting target outcomes

- Severe ADHD: safety concerns may be priority
- Treatment goals that make sense to the child
- Treatment goals that make sense to the parents

## Choosing an initial medication

- First decision: longer or shorter acting?
- Should relate to target goals
- Long acting obviates need for mid school day dose
- Especially important with older school aged and teens
- Short acting allows targeting times of day
- May be important for younger child in half day of school
- If target goal is school related only and parents are tolerant of behaviors at home

## Choosing an initial product

- Largely dictated by insurance coverage
- Many cover at least one long acting preparation
- Cost difference between generic shorter duration and name brand long acting may be > $100/mo, depending on dose.

## Choosing an initial dose

- Aim for lowest dose likely to be effective
- In past, starting routinely at very low dose, but safety at effective doses established with large randomized controlled studies
- Younger child, slight child, primarily inattentive: lower dose to start
- Older, or symptoms more severe: moderate doses to start

## Doses

- DEX higher potency than MPH
- Dosing Intervals
- Short acting: 2 to 4 doses per day
- Longer acting
- 1 dose per day
- Or 7 am dose long acting and 5pm dose short acting of same medication
- Ex: Concerta® or Ritalin LA® in am and generic MPH in late afternoon

## Doses

- Lower doses, per dose
- Short acting
- 5 – 10 mg. MPH, 5 mg. DEX
- Longer acting
- 10 – 27 mg. MPH; 5 – 10 mg DEX
- Moderate doses, per dose
- Short acting
- 20 mg. MPH, 10 – 20 mg. DEX
- Longer acting
- 39 – 54 mg MPH; 30 – 40 mg. DEX

## Doses

- Higher doses
- Short acting
- > 20 mg per dose MPH or DEX
- Or > 60 mg per day MPH or DEX
- Long acting
- > 72 mg per dose MPH,  > 40 mg DEX
- > 54 mg in younger child MPH, > 30 mg DEX
- Higher doses used in more severe cases
- Guidelines: titrate to benefit without side effects

## Monitoring medication

- Optimal frequency of follow up is not well studied
- Many recommend follow up visits every 3 to 4 months once dose is established
- Allows monitoring effectiveness
- Allows monitoring side effects

## Monitoring medication

- If intervals longer than every 4 months
- Potential for med to be continued when not effective
- Potential for med to be prematurely discontinued or other meds selected, which might have more side effects
- Potential for mild side effects to be unnecessarily tolerated for most of school year

## Monitoring medication

- Very young children and those with co-existing conditions need visits every 3 months when stable
- More difficult diagnostic challenge
- Greater possibility of developmental progress in symptoms for very young child
- More side effects in younger children
- Distinct possibility of under treated co-existing condition
- Possibility of co-existing condition primary, rather than ADHD

## Monitoring for side effects

- At all visits
- Blood pressure, pulse, height, weight
- Appetite, headache, abdominal pain, sleep
- Tics, mood changes, irritability
- “Rebound” phenomena
- Most side effects are responsive to changes in dose or timing

## Appetite suppression

- Expected in perhaps 80% patients
- For most children and families, awareness of need to provide good caloric intake prevents or solves problem
- Problem is more pronounced in younger children

## Appetite suppression

- Some children must find their own food and fail to gain weight on stimulants
- Some families are rigid about food and mealtime and children fail to gain on stimulants
- Some children fail to gain weight and this is not apparent until height is affected
- Illustrates importance of follow up visits

## Headache and “stomach ache”

- These may respond to taking medication with food
- Many kids, all ages, go to school without breakfast, are not hungry at lunch due to medication, and experience headaches, abdominal pain and mood changes
- May occur in first few days of medication, but usually not severe enough to interrupt activities

## Delayed sleep onset

- Important to establish baseline sleep patterns
- Recent research indicates difficulty with sleep onset may be associated with disorder rather than medication
- Other research indicates medication
- Usually responsive to timing of last dose

## Onset of tics, tic disorder

- Important to note baseline behaviors, mannerisms, family history of tics
- Tics may not be recognized as such by patient, family or teacher
- Not contraindication to treatment with stimulants

## Mood changes, irritability

- Unusual for this to occur at reasonable doses
- Some children sensitive to this effect for one of the stimulants, but not the other
- If other reasons cannot be found (such as new custody arrangements, loss of pet), this may be reason to change medication
- Not a fair trade off
- child may be more attentive and focused but feels unhappy or dysphoric

## “Rebound” phenomena

- Some researchers say this doesn’t exist
- Search for other causes of increased irritability toward end of school day or afternoon
- Not eating, siblings home alone
- May be responsive to lowering dose over day, with short acting
- 20 mg 7am, 20 mg. 11am, 10 mg. 3pm.

## Need to change dose

- A dose may be effective for 1 to 2 years, and then need adjusting
- A dose is not necessarily increased every year
- Summers, holidays, weekends off?
- Depends on target outcomes
- May be management of poor weight gain

## How long to treat?

- Double blind controlled study not often done clinically
- Cumbersome placebo production, hard to mask the product
- Expensive – not covered by insurance
- Adolescents often want to stop med
- Patient learns to use med for targeted outcomes and takes that skill into young adult years

## More than one medication for ADHD?

- Uncomplicated ADHD does not require more than one medication
- Most common rationale for more than one medication
- Severe and disabling symptoms
- Safety issues
- Co-existing conditions
- Depression, tic disorder, obsessive compulsive disorder

## Challenges of managing more than one medication

- Lack of guidance
- Difficulty discerning which needs to be adjusted
- Difficulty anticipating drug interactions
- Stimulants often among those used in combination pharmacotherapy