ICL 8.2: Psychophatmacology of Children & Neurodevelopmental Disorders

Question 1

what is the difference in pharmacokinetics of a kid/adolescent vs. an adult?

Answer 1

1. kids have smaller bodies, faster and more efficient metabolism
2. they also have more body water, less fat, less plasma albumin = ↑ drug volume of distribution
3. faster elimination = shorter drug plasma half life in children

treating with lower doses based on child weight/age may result in under-treatment

start low, go slow

Question 2

what is the DSM5 criteria for ADHD?

Answer 2

a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning/development, as characterized by (1) and/or (2) for at least 6 months before age 12

1. inattention
2. hyperactivity and impulsivity
3. combined

Question 3

what symptoms is ADHD medication targeting?

Answer 3

1. poor concentration/inattention
2. motor hyperactivity
3. impulsiveness

can also have additional benefits that help with disorganization, forgetfulness, multitasking, mood lability, and sleep regulation

Question 4

what are the 2 classes of medications used to treat ADHD?

Answer 4

1. stimulant medications

2. non-stimulant medications

Question 5

what are the characteristics of stimulant medications used to treat ADHD?

Answer 5

these are the GOLD STANDARD!!

1. safe/well tolerated overall
2. efficacious
3. fast onset of effect
4. flexible administration

Question 6

what are the characteristics of non-stimulant medications used to treat ADHD?

Answer 6

1. may have fewer side effects
2. not a controlled substance
3. no abuse potential

Question 7

what are the contraindications against using stimulants for ADHD treatment?

Answer 7

1. guardian preference
2. comorbid medical issues like HPT, CVD, structural cardiac abnormalities, glaucoma, hyperthyroidism
3. growth concerns
4. comorbid psychiatric issues like mood disorder or psychosis
5. substance abuse, concern for diversion

any of these should make you consider using a non-stimulant as a first line treatment

Question 8

which medications are stimulant medications used to treat ADHD?

Answer 8

1. amphetamine/dextroamphetamine (adderall/dexedrine)
2. methylphenidate (ritalin/concerta/fecalin/metadate/daytrana/quillivant)
3. lisdexamfetamine (vyvanse)

Question 9

what is the MOA of stimulants?

Answer 9

they block NE and dopamine re-uptake transporters –> this increases the NE and DA levels in the synaptic cleft

amphetamines also promote release of dopamine from the presynaptic vesicles

Question 10

what medical things do you need to check up on before starting someone on stimulants?

Answer 10

1. EKG is reasonable but it’s not mandatory
2. cardiac history

but the risk of dying of a sudden cardiac event is no more than the general population

3. physical exam
4. monitor vitals

Question 11

what medications do you start young kids vs. older kids on for ADHD?

Answer 11

if they’re under 6 years old, start with amphetamine/dextroamphetamine

older kids can trial AMPH or methylphenidate

typically start with immediate release and then transition to long acting medications as tolerated

Question 12

what are the only 2 medications approved for starting ADHD treatment in adults?

Answer 12

1. atomoxetine
2. lisdexamfetamine

others are approved for continuing treatment start prior to adulthood

Question 13

what are the side effects of stimulant medications?

Answer 13

1. decreased appetite
2. insomnia

other side effects can be headache, dizziness, increased pulse/blood pressure, nervousness, irritability, mood swings, tremor, nausea, weight loss, constipation/diarrhea, dry mouth, growth retardation, psychosis, anxiety

note: tics are NOT considered a side effect of stimulants

Question 14

which medications are non-stimulant medications used to treat ADHD?

Answer 14

1. α-2 agonists (clonidine/Kapvay; guanfacine/Tenex/Intuniv)
2. atomoxetine (Strattera)
3. bupropion (Wellbutrin)
4. tricyclic antidepressant (imipramine, desipramine, nortriptyline) –> not commonly used
5. modafinil (Provigil)
6. antipsychotics

Question 15

what is the MOA of α-2 agonist medications?

Answer 15

they are non-stimulant medications used to treat ADHD

there are high levels of α-2 receptors in the cortex and locus coeruleus they’re responsible for NE release into the prefrontal cortex so they regulate inattention, hyperactivity and impulsivity symptoms

so α-2 agonists help with hyperactivity, impulsivity, insomnia, aggression and anxiety

used as ADHD medication

Question 16

which class of medication can be used to augment stimulant treatment?

Answer 16

α-2 agonists

Question 17

what are some of the side effects of α-2 agonists?

Answer 17

1. fatigue
2. hypotension
3. dizziness
4. rebound hypertension/tachycardia if taken off medication
5. constipation
6. headache

Question 18

what are the side effects of atomoxetine?

Answer 18

aka Strattera
1. black box warning = suicidality (because it started as an antidepressant)

2. sedation
3. GI upset
4. increased heart rate and BP
5. liver damage (rare)
6. anxiety, irritability, mood lability

Question 19

what is the MOA of atomoxetine?

Answer 19

Strattera is a NE reuptake inhibitor at the presynaptic neuron

this increases dopamine in the prefrontal cortex

so it works differently than stimulant medications

used as ADHD medication

Question 20

what is the MOA of bupropion?

Answer 20

wellbutrin is a NE and dopamine reuptake inhibitor but it’s not as potent as other stimulants

can cause irritability, decreased appetite, insomnia, lower seizure threshold

used as ADHD treatment

Question 21

which tricyclic antidepressants are used to treat ADHD?

Answer 21

1. desipramine*
2. imipramine
3. nortriptyline
   note: they can be toxic if too much is taken and there’s a lot more side effects in children so the evidence supporting clinical use is low

Question 22

in what case would you use antipsychotics to treat ADHD?

Answer 22

antipsychotics are not FDA approved but they’re commonly used in cases of severe aggression or hyperactivity

haloperidol or chlorpromazine are used with severe behavioral disorders

Question 23

in what case would you use modafinil to treat ADHD?

Answer 23

prodigal/sparlon is FDA approved for narcolepsy, EDS with sleep apnea and shift work sleep disorder but there have been variable research results supporting its use for ADHD

the FDA actually pulled its approval because there’s increased risk of SJS in kids so it’s not really used much

Question 24

7 y/o male, 1st grader with previous diagnosis of ADHD,
Referred by school for concerns of inattention, hyperactivity, impulsivity
Pt reports he frequently gets into trouble at school for being off task, out of seat, distracted, distracting/interrupting others, and talking
Receives additional help with reading and writing at school
Being placed, not promoted, into 2nd grade d/t not meeting academic milestones
Enjoys recess, friends at school, doesn’t like learning because it takes too long
Struggles to get any homework done, he is distractible in activities at home
Pt otherwise is “happy,” sleep and appetite are good
He does at times get “fixated” on certain things per dad i.e. a new toy, the idea of a spooky story or concerns about sharks in the water, but generally is not an anxious boy.

Med hx: FH cardiac disease, arrythmia; no personal medical history. Pt met milestones, no issues during mothers pregnancy/delivery

Pt initially started with treatment behavioral therapy/interventions

Medical treatment:
EKG ordered, results normal
Started methylphenidate (immediate release), titrated up dose, no response
Changed to dextroamphetamine/amphetamine, symptoms decreased but significant appetite suppression limited adequate treatment
Changed to dextroamphetamine, titrated dose up to long acting formulation, titrated dose to adequate symptom improvement lasting through afternoon homework
Improvement in school performance, work completion, behaviors

Answer 24

cool

Question 25

which medications are used to treat oppositional defiant disorder?

Answer 25

there are no specific medications are indicated/FDA approved!

Question 26

how do you treat oppositional defiant disorder?

Answer 26

1. behavioral therapy 2. manage comobidities like ADHD, depression, anxiety, PTSD, insomnia, bipolar disorder, substance abuse etc. 3. parent training there is some bit of evidence for use of α-2 agonist

Question 27

what is the DSM criteria for autism spectrum disorder?

Answer 27

1. persistent deficits in social communication and social interaction across multiple contexts 2. restricted, repetitive patterns of behavior, interests, activities 3. symptoms present in early developmental period 4. symptoms are clinically impairing 5. not better explained by intellectual disability or global developmental delay, but frequently co-exist

Question 28

what symptoms is autism medication trying to treat?

Answer 28

1. “irritability” 2. mood lability 3. aggression 4. anxiety, perseveration, repetitiveness* 5. insomnia 6. hyperactivity 7. impulsivity 8. treating comorbidities (anxiety, depression, ADHD, insomnia)

Question 29

which medications are used to treat the symptoms of autism? which symptoms do they treat?

Answer 29

1. risperidone (resperdal) 2. aripiprazole (abilify) these are FDA approved for treating irritability, aggression and mood lability associated with autism spectrum disorder

Question 30

what off-label medications are used to treat autism spectrum disorder?

Answer 30

1. SSRIs like fluoxetine for anxiety, irritability, repetitive behaviors 2. α-2 agonists like clonidine/guanfacine for hyperactivity, impulsivity, irritability, anxiety, or insomnia 3. anticonvulsant/antiepileptic drugs for aggression and mood lability

Question 31

what new developments have been made with autism medications?

Answer 31

people are looking into oxytocin and vasopressin for treatment of ASD they're trying to block and/or increase vasopressin to improve social and communication skulls and repetitive behaviors

Question 32

what are the characteristics of tics in general?

Answer 32

affect up to 20% of children at some point usually mild & simple/isolated often go unnoticed may disappear with focused attention/fine motor activity, sleep typically resolve within one year all tics may worsen during times of increased stress, fatigue, illness

Question 33

what are the 2 main types of tic disorders?

Answer 33

1. persistent motor or vocal tic disorder | 2. Tourette's disorder

Question 34

what is persistent motor or vocal tic disorder?

Answer 34

1. single or multiple motor or vocal tics have been present but not both 2. tics may wax and wane in frequency but last > 1 year since onset 3. onset before age 18

Question 35

what is Tourette's disorder?

Answer 35

both multiple motor and one or more vocal tics but not necessarily concurrently

Question 36

how do you treat tics?

Answer 36

1. education, reassurance, monitoring 2. habit reversal therapy if they're frequent, embarrassing or cause discomfort you can try medications

Question 37

which medications are used to treat tics?

Answer 37

1. antipsychotics atypical = risperidone, aripiprazole, ziprasidone typical = haloperidol or pimozide --> pimozide isn't commonly used unless last resort because there's prolonged QT interval 2. α-2 agonists like guanfacine or clonidine which aren't FDA approved but commonly used as first line treatment and have lower side effect profile

Question 38

how do you treat insomnia before meds?

Answer 38

1. behavioral interventions 2. ask about caffeine, screen, exercise, medications 3. rule out other medical issues 4. refer for sleep evaluation if appropriate

Question 39

which medications can be used to treat insomnia?

Answer 39

1. melatonin 2. antihistamine 3. α-2 agonists 4. antidepressants

Question 40

how does melatonin help treat insomnia?

Answer 40

endogenous, pineal gland releases it naturally in circadian manner decreases sleep onset, increases total sleep time more isn’t always better (no evidence of dose-response relationship) unlikely habituation, hangover, dependence

Question 41

what is first line treatment for enuresis?

Answer 41

1. education 2. reassurance 3. medical workup to make sure nothing else it going on

Question 42

which medication can be used to treat enuresis?

Answer 42

1. desmopressin it's a synthetic vasopressin analog with low side effects however, there's a high relapse rate after discontinuation so it's really just used for special occasions like sleep overs or camp 2. tricyclic antidepressants like imipramine which stimulates vasopressin secretion, relaxes detrusor muscle and decreases REM sleep relapse rate is really high too so they're less effective and have higher side effects

Question 43

how do you treat mood, anxiety, and psychotic disorders in kids?

Answer 43

you basically use a lot of the same medications that are used in adults just keep in mind the pharmacodynamics and pharmacokinetics for pediatric patients and don't use benzodiazepines