Attention deficit hyperactivity disorder
1. Manifests in childhood with what kind of symptoms? 3
- These symptoms have effects on what?5
- Manifests in childhood with symptoms of
- hyperactivity,
- impulsivity, and/or
- inattention - Symptoms affect
- cognitive,
- academic,
- behavioral,
- emotional, and
- social functioning
Male to female ratio
- ___ for the predominantly hyperactive type
- ____ for the predominantly inattentive type
- 4:1
2. 2:1
ADHD is frequently associated with other psychiatric disorders
5
- Oppositional defiant disorder
- Conduct disorder
- Depression
- Anxiety disorder
- Learning disabilities
Neuropathogenesis of ADHD
2
- Functional brain imaging reveals decreased activation in the areas of the basal ganglion and anterior frontal lobe.
- Major neurotransmitters involved in ADHD are dopamine and norepinephrine
Dopamine:
1. Most of the dopamine sensitive neurons are located in the what?
- Dopamine system is associated with what? 5
- Dopamine limits and selects sensory information arriving from the where to the where?
- frontal lobe.
- Reward,
- attention,
- short term memory tasks
- Planning,
- motivation
- the thalamus to the forebrain
What the frontal lobe does
4
- Ability to project future consequences resulting from current actions
- The choice between good and bad actions (or better and best)
- The override and suppression of socially unacceptable responses
- The determination of similarities and differences between things or events
What is different about the brain function of those with ADHD?
3
- Decreased activation in the areas of the basal ganglion and anterior frontal lobe
- Increase in dopamine transporter activity thus clearing dopamine from the synapse too quickly
- The dopamine imbalance allows an inappropriate increase in norepinephrine activity
The basis of treatment of ADHD with what?
Methylphenidate
The administration of methylphenidate does what? 2
- Increases extracellular dopamine in the brain
- Changes the areas of function in the frontal lobe
In patients without ADHD methylphenidate does not have the same effect on frontal lobe function
DSM V criteria for ADHD
1-6- general symptoms
7-15- Inattentive symptoms
16-24 Hyperactivity symptoms
Need 6 or more symptoms of inattention or hyperactivity/impulsivity
5 or more for age 17 and older
- Symptoms inappropriate for the given age
- Negatively impacts social and academic or occupational activities
- Symptoms developed prior to age 12
- Symptoms present in 2 or more settings
- Symptoms present for at least 6 months
- Symptoms are not better explained by other psychiatric disorder(s)
- Failure to give close attention to detail
- Difficulty sustaining attention in task
- Failure to listen when spoken to directly
- Failure to follow instructions
- Difficulty organizing tasks and activities
- Reluctance to engage in tasks that require sustained mental effort
- Loses things necessary for tasks or activities
- Easy distractibility
- Forgetfulness in daily activities
- Fidgetiness with hands and feet or squirms in seat
- Difficulty remaining seated in class
- Excessive running or climbing in inappropriate situations
- Difficulty in engaging in quiet activities
- Is often “on-the-go” or acts as if “driven by a motor”
- Often talks excessively
- Excessive talking and blurting out answers before questions have been completed
- Difficulty awaiting turns (while waiting in line)
- Interrupting and intruding on others
Medical evaluation of ADHD?
3
- Parents and teacher need to fill out a form such as the Vanderbilt form
- Refer for vision and hearing tests
- Complete history, ROS and physical exam to rule out other causes and psychiatric illnesses
If history suggests may consider the following testing for ADHD:
4
- Blood lead level
- TSH
- Sleep study
- Neurology consult if concern for seizures or other neurologic disorder
Treatment of ADHD
2
- Stimulants (Ritalin, Adderall and Concerta) are the treatment of choice
- Behavioral therapy treatment
(has not been shown to reduce symptoms in absence of concurrent stimulant Rx (in a patient that truly has a diagnosis of ADHD!))
Criteria for initiation of pharmacotherapy for ADHD
8
- Complete diagnostic assessment that confirms ADHD
- ≥ 6 years old
- Parental consent
- School is cooperative (if dosing during school hours)
- No previous sensitivity to the chosen medication
- Normal heart rate and BP
- No history of seizure disorder (if so refer to neurology to treat ADHD too)
- Does not have Tourette syndrome, Autism spectrum disorder, anxiety disorder, or substance abuse among household members
Before starting therapy what do ADHD pts need?
4
- A comprehensive medical evaluation (see previous slide)
+ EKG (rule out arrhythmia) - Document pretreatment height, wt, BP, HR
- Document the presence of any of the following symptoms prior to treatment: general appetite, sleep pattern, headaches and abdominal pain
- Assess for substance use or abuse
- -Need treatment before starting ADHD meds
ADHD Pharmacology
Pretreatment education
5
- Meds are being prescribed to help with self control and ability to focus
- Benefits and potential risks
- Other potential risks
- The follow up protocol that is expected
- Patient specific treatment goals
Benefits vs potential risks of ADHD pharmacotherapy?
Emphasizing uncertainty about a causal association between serious CV risks to include sudden unexpected death and stimulants for children with cardiac symptoms or positive family history of heart disease
Other patient risks for pharmacotherapy for ADHD?
4
- Anorexia,
- insomnia,
- tics
- Priapism with Methylphenidate or Atomoxetine
Choice of Agent
If patient and parents agree to medications
First line? 2
Second line? 1
Stimulants are first line agent
- Methylphenidate (Ritalin)
- Dextroamphetamine (Adderall)
- Atomoxetine (Strattera) is an alternative (non stimulant)
General considerations that may affect medication choice in ADHD
10
- Daily duration of coverage needed
- Completion of homework or driving after school?
- Ability of child to swallow pills or capsules
- Time of day when target symptoms occur
- Desire to avoid administration at school
- Coexisting tic disorder (avoid stimulants)
- Coexisting emotional or behavioral condition
- Potential adverse effects
- History of substance abuse in patient or household member (avoid stimulants)
- Expense (short acting stimulants are least expensive)
The PROS of pharmacotherapy for ADHD
6
- Stimulant medications have a long record of safety and efficacy
Improves
- Core symptoms of ADHD
- Parent-child interactions
- Aggressive behavior
- Academic productivity and accuracy
- Improved self-esteem
The CONS of pharmacotherapy for ADHD
6
- Insufficient data to judge affect on long term academic performance
- ADHD symptoms tend to improve over time regardless of treatment modality
Does not significantly affect - Learning problems
- Reduced social skills
- Oppositional behavior
- Emotional problems
ADHD Pharmacology
Preschool children need what?
This age group needs referral to a Behavioral Health Specialist
Drug classes used in the treatment of ADHD
-Stimulants (schedule II controlled substance)
First line therapy
4
- Methylphenidate
- Amphetamines
- Detroamphetamine
- Detroamphetamine-amphetamine
Three other classes that may be used for ADHD treatment? 3
- Atomoxetine
- Alpha-2-adrenergic agonists
- Antidepressants
What are the antidepressants that we could use for ADHD? 2
- Tricyclics
2. Bupropion
Short acting stimulants: Methylphenidate
1. What are the short acting formulations? 2
- Adminitrations options? 3
- Time to onset of action ranges from _____minutes
- Duration of action is ____ hours
- Half-life is ____ hours
- Ritalin and Methylin
- Tablet, chewable tablet or liquid
- 20 to 60
- 3-5
- 2-3
Long acting stimulants: Methylphenidate
Two types of formualtions?
- Single pulse: Metadate ER, Methylin ER and Ritalin SR
Onset of action 20-60 min, duration of action 8 hrs - Sustained release capsules: Focalin XR (dexmethylphenidate), Metadate CD, Ritalin LA
- Onset of action 20-60 min, duration of action 9 hrs except for Focalin XR duration of action is 12 hrs
- Contain a mixture of immediate release & enteric coated delayed release beads
- Approximates BID dosing of the short-acting
Long acting stimulants: Methylphenidate
Osmotic release: Concerta
- Describe how it is administered?
- How many times a day?
- Onset of action? Duration of action?
- Immediate release on the outside then uses an osmotic pump to slowly release medication
- Approximates TID dosing of the short acting formula
- Onset of action 20-60 min, duration of action 12 hrs
Long acting stimulants: Methylphenidate
Oral suspension: Quillivan XR
-Onset and duration of action?
Onset of action 60 min, duration of action 12 hours
Transdermal: Daytrana
- Onset of action and duration?
- Effects last how long after removal?
- Onset of action 60 min, duration of action 12 hours
2. Effects last 3 hours post removal of the patch
Short acting stimulants: Amphetamines
2
Name the brand names of each, onset and duration of action?
- Detroamphetamine
- Dexedrine, Dextrostat, Procentra (Oral soln)
- Onset of action 20 min, duration of action 4-6 hrs - Amphetamine-dextroamphetamine
- Adderall
- Onset of action 20 min, duration of action 4-6 hrs
Long acting stimulants: Amphetamines
- Lisdexamfetamine (Vyvanase)
- Prodrug of what?
- Pharmacologically actove after what?
- Why was it designed?
- Onset of action, duration of action? - Dextroamphetamine SR (Dexedrine spansule)
- Combo of what?
- Onset, duration of action? - Amphetamine-dextroamphetamine (Adderall XR)
- What is it a combo of?
- Onset of action, duration?
- Prodrug of dextroamphetamine
- Pharmacologically activated after oral ingestion
- Was designed to discourage drug misuse
- Onset of action 1hr, duration of action 10-12 hrs
- Combo of immediate and continuous release meds
- Onset of action 20 min, duration of action 6-8 hrs
- Combo of immediate and continuous release meds
- Onset of action 20 min, duration of action 8-10 hrs
Stimulant therapy is first line
Which meds are equally effective? 3
Methylphenidate, dexmethylphenidate and amphetamines are equally effective
Have similar side effect profiles
Stimulant therapy
Short acting agents
- Initial rx in children of what age?
- Can be used for what else?
- less than 6
2. Or can be used to determine optimal dosing before switching to a long acting agent
Stimulant therapy
Longer acting preparation
1. May be used initially in what ages?
2. Starting at what?
- May be used initially in age > 6
2. Starting at the lowest dose and titrating up
Stimulants: Dose titration
State the initial, titration increments, and max doses for the following:
- Methylphenidate SR (Ritalin)
- Methylphenidate LA (Ritalin LA)
- Methylphenidate ER (Concerta)
- Initial dose 20 mg
Increments of 20 mg per day q 3-7 days
Maximum dose: less than 50kg = 60 mg; >50Kg =100 mg - Initial dose 10 mg
Increments of 10 mg per dose q 3-7 days
Maximum dose: less than 50kg = 60 mg; >50mg =100 mg - Initial dose 18mg
Increments of 9-18 mg per dose q 3-7 days
Maximum dose: less than 13 yo = 54 mg; >13 yo = 72 mg
What are the Alpha-2-adrenergic agonists?
2
Clonidine (Catapres)
Guanfacine (Tenex)
Atomoxetine (Strattera)
State the initial, titration increments, and max doses for the following:
Dose titration for Children older than six
1. Weigh ≤ 70 kg
2. Weigh ≥ 70 kg
- May take how long before effects are noted?
- Weigh ≤ 70 kg
- Initial dose 0.5mg/kg per day x 3 days
- Increase to 1.2mg/kg/day after 3 days
- Max dose lesser of 1.4mg/kg or 100 mg per day - Weigh ≥ 70 kg
- Initial dose 40 mg
- Increase to 80 mg after a minimum of 3 days
- After 2-4 weeks may increase to 100 mg
May take 1-2 weeks before effects are noted
Monitoring response to therapy and assessment for side effects
6
- Assess weekly during titration stage
- -(can last 1-3 months) - Monitored behavior through parent and teacher feedback
- After titration stage patients seen monthly to monitor weight, heart rate and BP until on a stable dose without new side effects
- Optimal dose is where there are favorable outcomes with minimal side effects
- When does the side effect occur in relation to administration?
- Is the effect related to a coexisting disorder or environmental stressor?
Mild adverse effects may resolve with time or adjusting any of the following? 3
- Dose
- Time of administration
- Formulation of medication
Evaluate for these side effects at every follow up visit
9
- Decreased appetite
- Poor growth
- Dizziness
- Insomnia/Nightmares
- Mood lability
- Rebound
- Tics
- Psychosis
- Diversion and misuse
Managing decreased appetite
3
- Give at or after a meal
- Encourage child to eat nutrient dense foods (no empty calories)
- Offer food that the child likes for noon meal
Managing medication side effects
- Poor growth? 1
- Dizziness? 3
- Insomnia or Nightmares? 4
- Poor Growth
- Drug holidays may be beneficial - Dizziness
- Monitor blood pressure and pulse
- Ensure adequate fluid intake
- If associated with peak effect, try longer acting preparation - Insomnia or nightmares
- Establish a bedtime routine
- Good sleep hygiene habits
- Omit or reduce the last does of the day
- If using long acting preparation consider short acting
Managing medication side effects: Mood lability
Symptoms that may occur as the medication wears off can be averted by using a longer acting formulation or increasing from BID to TID if short acting
Such as? 3
Sometimes mood changes can occur at peak concentration
How can we manage this?
- Sadness
- Irritability
- Increased activity
Try reducing dose or switching to longer acting
Managing medication side effects
- Rebound (symptoms that occur as meds wear off)?
- Tics?
- Rebound (symptoms that occur as meds wear off)
- May improve by stepping dose down a the end of day - Tics
- Conduct a drug trial at different doses including no medication to be sure that they are related to meds
Managing medication side effects
Psychosis symtpoms? 3
What do we have to do before we make the diagnosis?
If this checks out how do we manage? 2
Psychosis
- Suicidality
- Hallucinations
- Increased aggression
- Verify dose is appropriate and medication is administered as prescribed
- If so, discontinue stimulant (can be done abruptly)
- Refer to mental health specialist
Further medication management
Diversion and misuse: how do we manage this?
4
- Monitor symptoms and prescription refills for evidence of misuse or diversion
- Long acting stimulants have less potential for abuse
- Keep track of prescription dates
- Open discussion
Reasons for treatment failure
4
Management of this? 2
- Lack of adherence to the medication regimen?
- Possibility of medication diversion
- Are treatment goals and expectations realistic?
- Is there a comorbid psychiatric diagnosis?
- Can try another stimulant medication
- If fail multiple stimulants or intolerable side effects then trial atomoxetine or an alpha-2 adrenergic
- What are Drug Holidays?
2. What is this not an option for? 2
- Discontinuation of stimulant medication on weekends or during the summer
Decide on a case by case basis - Not an option for
- atomoxetine or
- alpha-2-adrenergic agonists because of the extended half life
Maintenance of Therapy
- Dosing at?
- F/U when?
- Continue to monitor what? 4
- Once on a stable dose
- follow up in the office should be every 3-6 months
- Continue to monitor
- ht,
- wt,
- BP,
- HR
Termination of Therapy
Which meds do we need to taper off 2 and which do we not 2?
Alpha-2-adrenergic agonists and tricyclics should taper off over several weeks
May abruptly discontinue stimulants or atomoxetine
Ritalin (Methylphenidate)
1. Acts on what receptors? 2
Acts on dopamine and norepinephrine to block reuptake
- Which drugs are short acting?
- long acting?
- Longer acting?
- Longest acting?
- Shortest acting: Ritalin & Methylin
- Long acting: Metadate ER, Methylin ER, Ritalin SR
- Longer acting: Focalin XR, Metadate CD, Ritalin LA
- Longest acting: Concerta, Quillivan XR, Daytrana
Ritalin (Methylphenidate)
SE? 5
Disadvantage?
Schedule
- Anxiety
- Weight loss
- Psychiatric symptoms: psychosis, aggression, hallucinations
- Heart problems in at risk people
- Easy bruising
High potential for addiction and abuse
Schedule II drug
Amphetamine-dextroamphetamine (Adderall)
- Disadvantages? 3
- Efficacy?
- SE? 4
- High potential for abuse (schedule II)
- May lead to drug dependence
- Extremely popular
- May be slightly more effective than Ritalin
- Side effects:
- Anxiety
- Weight loss
- Psychosis, hallucinations, aggression
- Heart problems in at risk people (sudden death)
Dextroamphetamine (Dexedrine)
- Prevuiously used for what?
- Among the most effectively treatment for what?
- Schedule?
- Major complication?
- Previously used for OTC diet pill
- Among the most effective treatment for ADHD
- Schedule II
- Sudden death in people that have heart problems or cardiac defects
Dextroamphetamine (Dexedrine)
- Heart related problems including? 3
- Psychiatric problems? 2
- Children and Teenagers? 3
- Heart related problems including
- Sudden death in people that have heart problems or defects
- Sudden death, stroke and heart attack in adults
- Increased blood pressure and heart rate - Psychiatric problems:
- New or worse behavior and thought problems
- New or worse bipolar - Children and Teenagers
- Seeing things or hearing voices
- Believing things that are not true
- New manic symptoms
Lisdexamphetamine (Vyvanase)
- Converted to what after oral ingestion?
- Disadvantage?
- Abuse potential?
- Amphetamines cause release of catecholamines (primarily which ones?) from their storage sites in the presynaptic nerve terminals?
- A less significant mechanism may include what?
- Converted to dextroamphetamine after oral ingestion
- No generic
- Less addictive but still a schedule II drug
- dopamine and norepinephrine
- their ability to block the reuptake of catecholamines by competitive inhibition
Atomoxetine (Strattera)
- Works on what NT?
- Initially tested for what?
- BBW?
- Disadvantage?
- Common SE?
- Works on norepinephrine
- Initially tested for depression but did not do much
- Black box label increased risk of suicidal behavior less than 25y
- Expensive
- Most common side effects: dry mouth, insomnia, nausea, decreased appetite, constipation, decreased libido, erectile dysfunction, urinary hesitancy, dizziness, and sweating1-2 weeks to notice effects
Atomoxetine (Strattera)
- Risk of what?
- Should be monitored closely for what?
- SE?
- Risk of suicidal ideation in children and adolescents
- Weigh risk vs. benefits - Should be monitored closely for suicidal thinking & behavior
- Families and caregivers should be advised of the need for close observation and communication with the provider
- Side effects
- Chest pain, shortness of breath, irregular heart beat
- Unusual thoughts or behavior, aggression, hallucinations
- Nausea, abdominal pain, loss of appetite, jaundice
Extended release guanfacine (Intuniv)
- What class of drug?
- SE?6
- Caution in who? 2
- Alpha-2-adrenergic agonist (antihypertensive)
- Approved for the treatment of ADHD - Side effects
- Fast or slow heart rate
- Pounding heartbeat, chest tightness
- Numbness or tingling
- High rate of fainting
- Depression
- Blood pressure problems (low) - Caution with kidney or liver disease
Bupropion (Wellbutrin)
- Alternative treatment for what?
- SE? 2
- ADHD
- Side effects:
- Anxiety,
- insomnia
DO NOT use stimulants with a history of what? 4
- substance abuse,
- structural heart defects,
- arrhythmia or
- increased CV risk profile
Vanderbilt assessment scales for who? 2
Consults to who? 3
- Parents and teachers
- Peds Developmental Clinic (if available)
- Behavioral Health (Preschool age children and adults for sure)
- Optometry and Audiology