ICL 8.2: Psychophatmacology of Children & Neurodevelopmental Disorders Flashcards
what is the difference in pharmacokinetics of a kid/adolescent vs. an adult?
- kids have smaller bodies, faster and more efficient metabolism
- they also have more body water, less fat, less plasma albumin = ↑ drug volume of distribution
- 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
what is the DSM5 criteria for ADHD?
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
- inattention
- hyperactivity and impulsivity
- combined
what symptoms is ADHD medication targeting?
- poor concentration/inattention
- motor hyperactivity
- impulsiveness
can also have additional benefits that help with disorganization, forgetfulness, multitasking, mood lability, and sleep regulation
what are the 2 classes of medications used to treat ADHD?
- stimulant medications
2. non-stimulant medications
what are the characteristics of stimulant medications used to treat ADHD?
these are the GOLD STANDARD!!
- safe/well tolerated overall
- efficacious
- fast onset of effect
- flexible administration
what are the characteristics of non-stimulant medications used to treat ADHD?
- may have fewer side effects
- not a controlled substance
- no abuse potential
what are the contraindications against using stimulants for ADHD treatment?
- guardian preference
- comorbid medical issues like HPT, CVD, structural cardiac abnormalities, glaucoma, hyperthyroidism
- growth concerns
- comorbid psychiatric issues like mood disorder or psychosis
- substance abuse, concern for diversion
any of these should make you consider using a non-stimulant as a first line treatment
which medications are stimulant medications used to treat ADHD?
- amphetamine/dextroamphetamine (adderall/dexedrine)
- methylphenidate (ritalin/concerta/fecalin/metadate/daytrana/quillivant)
- lisdexamfetamine (vyvanse)
what is the MOA of stimulants?
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
what medical things do you need to check up on before starting someone on stimulants?
- EKG is reasonable but it’s not mandatory
- cardiac history
but the risk of dying of a sudden cardiac event is no more than the general population
- physical exam
- monitor vitals
what medications do you start young kids vs. older kids on for ADHD?
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
what are the only 2 medications approved for starting ADHD treatment in adults?
- atomoxetine
- lisdexamfetamine
others are approved for continuing treatment start prior to adulthood
what are the side effects of stimulant medications?
- decreased appetite
- 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
which medications are non-stimulant medications used to treat ADHD?
- α-2 agonists (clonidine/Kapvay; guanfacine/Tenex/Intuniv)
- atomoxetine (Strattera)
- bupropion (Wellbutrin)
- tricyclic antidepressant (imipramine, desipramine, nortriptyline) –> not commonly used
- modafinil (Provigil)
- antipsychotics
what is the MOA of α-2 agonist medications?
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
which class of medication can be used to augment stimulant treatment?
α-2 agonists
what are some of the side effects of α-2 agonists?
- fatigue
- hypotension
- dizziness
- rebound hypertension/tachycardia if taken off medication
- constipation
- headache
what are the side effects of atomoxetine?
aka Strattera
1. black box warning = suicidality (because it started as an antidepressant)
- sedation
- GI upset
- increased heart rate and BP
- liver damage (rare)
- anxiety, irritability, mood lability
what is the MOA of atomoxetine?
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
what is the MOA of bupropion?
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
which tricyclic antidepressants are used to treat ADHD?
- desipramine*
- imipramine
- 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
in what case would you use antipsychotics to treat ADHD?
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
in what case would you use modafinil to treat ADHD?
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
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
cool
which medications are used to treat oppositional defiant disorder?
there are no specific medications are indicated/FDA approved!
how do you treat oppositional defiant disorder?
- behavioral therapy
- manage comobidities like ADHD, depression, anxiety, PTSD, insomnia, bipolar disorder, substance abuse etc.
- parent training
there is some bit of evidence for use of α-2 agonist
what is the DSM criteria for autism spectrum disorder?
- persistent deficits in social communication and social interaction across multiple contexts
- restricted, repetitive patterns of behavior, interests, activities
- symptoms present in early developmental period
- symptoms are clinically impairing
- not better explained by intellectual disability or global developmental delay, but frequently co-exist
what symptoms is autism medication trying to treat?
- “irritability”
- mood lability
- aggression
- anxiety, perseveration, repetitiveness*
- insomnia
- hyperactivity
- impulsivity
- treating comorbidities (anxiety, depression, ADHD, insomnia)
which medications are used to treat the symptoms of autism? which symptoms do they treat?
- risperidone (resperdal)
- aripiprazole (abilify)
these are FDA approved for treating irritability, aggression and mood lability associated with autism spectrum disorder
what off-label medications are used to treat autism spectrum disorder?
- SSRIs like fluoxetine for anxiety, irritability, repetitive behaviors
- α-2 agonists like clonidine/guanfacine for hyperactivity, impulsivity, irritability, anxiety, or insomnia
- anticonvulsant/antiepileptic drugs for aggression and mood lability
what new developments have been made with autism medications?
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
what are the characteristics of tics in general?
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
what are the 2 main types of tic disorders?
- persistent motor or vocal tic disorder
2. Tourette’s disorder
what is persistent motor or vocal tic disorder?
- single or multiple motor or vocal tics have been present but not both
- tics may wax and wane in frequency but last > 1 year since onset
- onset before age 18
what is Tourette’s disorder?
both multiple motor and one or more vocal tics but not necessarily concurrently
how do you treat tics?
- education, reassurance, monitoring
- habit reversal therapy
if they’re frequent, embarrassing or cause discomfort you can try medications
which medications are used to treat tics?
- antipsychotics
atypical = risperidone, aripiprazole, ziprasidone
typical = haloperidol or pimozide –> pimozide isn’t commonly used unless last resort because there’s prolonged QT interval
- 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
how do you treat insomnia before meds?
- behavioral interventions
- ask about caffeine, screen, exercise, medications
- rule out other medical issues
- refer for sleep evaluation if appropriate
which medications can be used to treat insomnia?
- melatonin
- antihistamine
- α-2 agonists
- antidepressants
how does melatonin help treat insomnia?
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
what is first line treatment for enuresis?
- education
- reassurance
- medical workup to make sure nothing else it going on
which medication can be used to treat enuresis?
- 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
- 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
how do you treat mood, anxiety, and psychotic disorders in kids?
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
