ADHD Therapeutics - Brian Haggblom Flashcards
What are the three core types of ADHD?
- Inattention (20-30%)
- Hyperactivity (5-15%)
- Combination (55-65%)
What are some characteristics of the inattention type of ADHD?
Inability to complete tasks, sustain attention, organize work
What are some of the characteristics of the hyperactive type of ADHD?
Inability to inhibit motor behaviors or responses.
What is the percent of people in the US who have ADHD?
4.4%
What percentage of children in the US have ADHD in 2011? When is it diagnosed?
11%. It is diagnosed at ages 4-17 years old.
Where in the US is the greater concentration of these recent diagnoses?
In the South
What abnormalities in the brain are exhibited in those with ADHD?
Executive function
Memory impairments
Information processing speed deficits
Decrease in catecholaminergic nature of brain circuits (low dopamine and NE in frontal)
Is there a genetic link in ADHD?
Yes, there seems to be. Risk is increased 2-8 times in parents/siblings/children.
What possible causes of ADHD are being researched?
- Brain injury
- Exposure to environmental (lead) during pregnancy/at young age
- Alcohol/tobacco use during pregnancy
- Low birth weight
- Premature birth
Is it thought that eating too much sugar or watching too much TV causes ADHD?
No, but they might make symptoms worse.
What are requirements for diagnosis common to all three types of ADHD?
- Symptoms need to be present prior to age 12
- must be present in 2 or more settings
- must significantly interfere with reduced level of functioning
- Rule out other causes for symptoms (other mental disorders)
As you get older and have ADHD, what types of things are you more at risk for?
- Increased risk of self-injury
- Driving mistakes
- Education hardships
- Substance use
- Persistence of symptoms
- Employment hardships
What are the goals of ADHD treatment?
- Improved relationships, improved academic performance, improved rule following
- Decreased hyperactivity symptoms, impulsivity symptoms, inattention symptoms.
- Promote independence
What non-pharmalogical treatment modalities are available for treating ADHD?
- Behavioral interventions (apps that block out social media)
- School based interventions (sit next to teacher)
- Social skills training (help with fighting, impulsiveness)
- Dietary interventions (fatty acid supplementation?)
What are the first line therapy for ADHD?
Stimulants, including methylphenidate and amphetamines.
What are the second-line therapy for ADHD?
Non-stimulants, such as atomoxetine, alpha-2 agonists, bupropion, TCA’s
Methylphenidate
- CNS stimulant
- blocks reuptake of NE and dopamine
- Fast onset
- CYP3A4 metabolism
- interacts with carbazepines, MAOIs, TCAs
Amphetamines
- CNS stimulant
- blocks reuptake of NE and dopamine
- Fast onset
- CYP2D6 metabolism
- interacts with paroxetine, fluoxetine, bupropion, MAOIs
What interval should you titrate by for stimulants in ADHD treatment?
Weekly to monthly to evaluate dose.
What is the latest in the day that you should take an IR stimulant?
4pm. Can also take a morning and a noon dose. ER can take only once a day in the morning.
How many stimulants should you try before moving on to a second-line agent?
Probably two stimulants, but it really depends on the patient.
What dosage forms are available for stimulants?
- Capsules (swallowed or sprinkled)
- Suspension
- Solution
- Chewable tablets
- Transdermal patch (Daytrana - place on hip and alternate each day. Wear for 9 hours)
What are some side effects that you can experience with stimulants? What can help?
- Dry mouth (chew gum)
- Insomnia (give as early as possible, d/c evening dose, sedating drug @ bedtime)
- Irritability (evaluate for comorbid bipolar disorder, reduce dose, consider mood stabilizer)
- Diminished appetite (eat a high calorie meal when the stimulant effects are low)
- Increased BP/HR (monitor closely)
- Hallucinations (d/c stimulant)
How much does HR and BP usually increase with a stimulant?
3-5mmHG increase in BP and 5bpm increase in heart rate
When should BP and HR be monitored for stimulant treatment?
At induction and throughout the course of treatment.
In kids especially, what should you watch out for with stimulants?
Decreases in height and weight (Decreased appetite and alteration of secretion of growth hormone)
What does amphetamine/methylphenidate have a black box warning for?
Misuse or addiction. Prolonged use or abuse may lead to drug dependence. Serious adverse cardiovascular reactions may occur or sudden death
What monitoring should be in place for stimulants?
- Safety (BP and HR, weight, height, AE)
- Adherence to treatment plan
- meeting treatment goals
- Occurrence of core ADHD symptoms
- Adverse effects of therapy
What are some thoughts about drug holidays from stimulants?
- They may be helpful to assess efficacy of dose and treatment
- Maybe not, because the symptoms would still be present without school.
- May cause negative side effects on learning, socialization, and self-image
- Can allow catch-up for growth/weight
- Can help manage tolerable side effects
Atomoxetine
- No/little abuse potential
- May take 4-6 weeks for full effect
- Inhibits NE reuptake, which increases NE and dopamine synaptically
- Black box warning for suicidality, increase ddepression
What is atomoxetine indicated for first-line?
For substance abuse problems, with comorbid anxiety, or tics
What kind of side effects does atomoxetine cause?
Similar to stimulant side effects… same mechanism.
Bupropion
- 2nd line
- No abuse potential
- Inhibits neuronal uptake of dopamine and NE
- CYP2D6, lowers seizure threshold
- excreted through kidneys
- may cause insomnia, takes several weeks for full effect
How do you dose bupropion in children?
By weight. 6mg/kg/day, BID. Start low at 37.5mg/day
What is the response to bupropion typically?
Only 40% reduction in symptoms, and 70-80% respond
What may be used in conjunction with stimulants?
Bupropion can be used with methylphenidate, but has a drug interaction with amphetamines.
What is a positive SE associated with bupropion?
Decrease in weight/appetite
What TCA’s are sed 2nd or 3rd line for ADHD?
Imipramine, desipramine, amitriptyline, nortiptyline
TCA’s
- Slow onset (up to 6 weeks)
- 40-50% reduction in symptoms
- Inhibits reuptake of serotonin and NE
- Useful in comorbid depression, anxiety, compulsions
- Adjunct for treating tics or insomnia from stimulants
What monitoring should you have in place for TCAs? What bad SEs are there?
- EKG
- Anticholinergic effects monitoring, dizziness
- overdose can be fatal
Guanfacine ER (intuniv)
- mostly used for children
- originally used to treat hypertension
- alpha2 adrenergic receptor agonist (decrease heart rate , block baroreflex). Increased stimulation of these receptors in the prefrontal cortex results in enhanced executive function, improvements in memory
- slow onset
Is guanfacine best in adjunctive or mono therapy?
Either one. it is less effective than stimulants, and more effective against hyperactive/impulsive symptoms than inattention.
How do you dose guanfacine? How do you start and taper off?
By weight. Start at 0.05-0.12mg/kg/day and titrate weekly. When stopping, titrate downward 1mg every 3-7 days.
What are some side effects of guanfacine?
Hypotension, sedation, dizziness
Clonidine ER
- central alpha2 adrenergic receptors stimulated, causes decrease in HR
- slow onset, may take weeks.
- hepatic metabolism
- blocks baroreflex
- IR used off-label
When is clonidine useful
- As adjunct with stimulants for treating hyperactive symptoms or stimulant AEs
- Treats hyperactivity symptoms over inattention
What off-label medications can be used to treat ADHD?
- Guanfacine IR
- Clonidine IR
- Clonidine patches
What drug interactions are involved with alpha-2 agonists? What increases their effects and what decreases their effects?
- Increases effects: Antipsychotics, opioids may enhance hypotension. CNS depressants, beta blockers (rebound hypertension when removed)
- Decrease effects: TCAs (may decrease antihypertensive effect)
What is CHADD?
An ADHD help group for parents, a national resource center
