Exam 4: ADHD Flashcards
physiolgoic risk factors of developing ADHD
- Male
- First degree relative diagnosed
- Minor physical abnormalities (hypertelorism, highly arched palate, low set ears)
- Motor delays, neurological soft signs
- VLBW 2-3x risk for ADHD!
Environmental risk factors of developing ADHD
- fetal alcohol syndrome
- Lead poisoning
- meningitis
- obstetric adversity
- maternal smoking
- adverse parent child relationship
- PTSD
Describe pathophysiology of ADHD
Decrease brain volume/reduced activty = attention deficit
* Decreased activation of ventral striatum
* Default mode network overactivity (active attention supression)
How do stimulants work?
- block DA and NE reuptake (MPH)
- increase catecholamine release (AMP)
- inhibit MAO
MPH
* Selective inhibits presynaptic reuptake of DA & NE
* more action on DA > NE
* Supresses default mode network overactivity!!!!
AMP
* Increase release of DA and NE into synapse from the presynaptic nerve terminal (enhance NE release in periphery)
* At high doses, stimulates 5HT release too (agonist)
* high fat meal delay time to [peak]
Treatment for primary ADHD diagnosis
1) Stimulants (FDA)
* MPH, d-MPH, ser-dex-MPH
* AMP, d-AMP, lis-dex-AMP
2) Non-stimulants
* NE reuptake inhibitorsm (FDA)
* alpha adrenergic receptor agonists (FDA)
* Other (Bupropion, TCAs, Lithium, APS)
AMP FDA approved for ≥3 y.o
IR forms ONLY
2. Dexedrine (d-AMP)
2. Evekeo, Adderal (AMP)
FDA approval
MPH approved for ≥3 y.o?
IR forms only of MPH
not fda approved
but recommended by guidelines for 4+
AMP FDA approved for ≥6 y.o
FDA approved
- Vyvanse (lis-d-AMP)
- Dynavel XR (AMP ER)
- Adxenys XR (AMP ER)
- Adderal XR (AMP ER)
- Xelstrym TD (d-AMP)
MPH FDA approved for ≥6 y.o
- Ritalin IR/SR/LA (MPH IR/SR/ER)
- Methylin ER (MPH ER)
- Focalin IR/XR (d-MPH IR/ER)
- Metadate CD (MPH modified release)
- Cotempla XR (MPH ODT)
- Jornay PM (MPH ER cap)
- Quillivent/Quillichew (susp/chew)
- Adhansia XR (MPH layer)
- Daytrana TD (MPH TD)
AMP FDA approved for ≥13 y.o
Mydayis (mixed AMP/d-AMP XR)
AMP products are preferred in which age group?
Adults
MPH products are preferred in which age group?
Children
however only AMP IR FDA approved <5
Which MPH products are 30% IR/70% ER?
MPH ER, MPHCD
* ritalin, methylin
* metadate ER/CD
* Quillivant XR/Quillichew
Which AMP products are 50% IR/50% ER?
Mixed AMP-XR salts (ex: Adderal XR)
Which MPH products are 50% IR/50% ER?
MPH LA
* ritalin LA
Dex-MPH XR
* Focalin XR
AMP products that require re-titration
AMP sulfate XR solution (Dynavel)
AMP XR ODT/ER suspension (Adzenys)
mixed AMP ER (Mydayis)
MPH products that require re-titration
Jornay PM
Cotempla XR ODT (?)
Azstarys (?) (ser-dex-MPH)
prior to diagnosis, rule out alternative causes
- learning disability
- situation stressors
- oppositional defiant disorder
- conduct disorders
- Tics/tourettes
- sleep disorder
- mood disorder
DSM5 ADHD
- Sx before 12 y/o
- impairment ≥2 places, sx documented
- sx interfere w/ functioning
- sx not d/t other idsorder
- sx: hyperactivity/inattention + impulsivity
> 6 or more present at least 6 months
> if ≥17 y/o, at least 5 sx required
School age ADHD presentation (6-11)
- difficulty at school
- combined: inattentive + hyperactive/impulse
- Comorbid: ODD, conduct disorder, aggression –> risk for delinquincy and SUD
Adolescent ADHD presentation (12-18)
Inattention/impulsive > hyperactive
sig. functional impairment
higher rate delinquincy/drug/etoh use
speeding/mva
Pre-School ADHD presentation (3-5)
excessive motor activity
intense tamper tantrum
preschool/school nonpharm
fam education on adhd
train behavior modification
behavioral classroom management (BCM)
Adolescent nonpharm
Break up assignments
structure schedule
behavioral peer interventions (BPI)
Adolscent/adult nonpharm
ADHD CBT
Metacognitive therapy (2hr/week x 12 wks)
Predominant comorbidity?
- Tourettes
- BP/severe aggression
- Anxiety/depression
Tourretes dx
- DA antagonist/A2 agonist
- dash of stimulant/atomoxetine/a2 agonist
- alt DA antagonist or a2 agonist
BP/severe agression dx
- atypical APS/lithium/anticonvulsant
- +dash of stimulant (careful of mania)
- alt or add mood stabilizer
Anxiety/depression dx
- antidepressant
- stimulant
- Alt. antidepressant
Characteristics of IR stimulants
- lower cost
- less insomnia, faster onset
- fewer growth related ADR
- short half life, frequent dosing
Characteristics of ER stimulants
- more insomnia, slower onset
- more growth related ADR
- long half life, Qday dosing, better adherence
General stimulants ADR
- Psych: mania, agression, anxiety
- Cardiac: slight increase HR/BP, avoid if cardiac (SEVERE HTN, arrythmia, HF, recent MI) – prefer MPH over AMP if cardiac
- Growth (barely, a couple cm, use IR to avoid)
General stimulant DDIs
antacid/ppi/h2ra
* Increase MPH IR absorption
* decrease MPH ER absorption
* Increase AMP absorption (PPI only)
* decrease AMP excretion (antacids only)
Acid (fruit juice)
* decrease AMP absorption
Food effect
* delay time to onset
*Additive if coffee/smoke/other psycho stim
* alcohol = stimulant dump
CYP 2D6 inhibitors (bup/fluox)
* increase mixed AMP exposure
Which forms of stimulants can be opened into applesauce?
Metadate CD (MPH CD)
Ritalin LA (MPH LA)
Adderal XR (mixed AMP XR)
Ritalin LA pearls
- applesauce
- better for severe morning sx than CD/MLR
Most MPH doses are 60mg MDD except:
Aptensio XR (MLR)
* 10 QD
Adhansia XR (MLR)
* 25 QD
Cotempia XR ODT
* 17.3 QD
Daytrana TD
* 10-30
Dex-MPH IR/ER
* MDD 20 (IR =bid dosing)
* 1/2 dose of MPH
Ser-Dex-MPH
* 52.3mg
MPH PM
* 20-100 QD
MPH XR suspension pearls
- shake virogrously ≥10sec
- when reconstituted, good for 4 months
MPH OROS pearls
Swallow whole - see shell in toilet
afternoon sx control better than d-MPH XR
MPH MLR pearls
has larger ER ratio
Better for rebound afternoon sx
Aptensio XR
Dex-MPH IR pearls
not better than MPH
1/2 dose of MPH
MDD 20 mg
5-10mg BID
Dex-MPH XR pearls
50/50
2 peak: 1.5hr post, 6.5 hr post
afternoon sx control not as good as OROS
d-MPH/ser-d-MPH
Ser-d-MPH is prodrug
RISK OF SUICIDAL IDEATION
MPH PM pearls
Jornay PM (MPH ER)
give between 6:30-9:30 PM
DO NOT GIVE IN AM
LONG DURATION 24-36 hrs
20 mg QHS –> MDD 100mg
DELEXIS DDS: multilayer DR/ER/CORE
* DR layer: 10 hours: ≤5% drug absorbed (≥10 hr onset)
* ER layer: dissolve throughout day, 14 hr to peak
Cotempla XR ODT pearls
Don’t push tab through foil
ORAL dissolve
start 17.3 QAM, increase weekly in 8.6-17.3 increments to MDD 51.8 mg
MPH TD pearls
Daytrana TD
6-17 years
10mg-30 mg / 9 hr
hip only
effect 1hr after removal (up to 3)
>50% drug left in patch
BBW: leukoderma hypopigmentaiotn
dAMP TD pearls
Xelstrym
≥6 y.o + adults
4.5 - 18 mg/9hrs
hip, upper arm/back, chest, flank
drug effect 3 hrs after removal
< 10% dAMP remains in patch
pain, itchiness, better tolerated
What stimulant has BBW for leukoderma/hypopigmentation
MPH TD (Daytrana)
Most AMP doses are 40 MDD except:
AMP sulf
* XR solution: MDD 20 mg
* XR ODT/ER susp: 6.3-12.5 mg QD
Mixed AMP XR salts: MDD 30mg (?6-11)
dAMP TD: MDD 18mg/9hr
lis-dAMP: MDD 70mg
AMP ER solution pearls
Dyanavel XR
≥ 6 y/o
2.5-5mg QDay (max 20)
RETITRATE
ADR
- nosebleed
- allergic rhinitis….
- upper GI pain
AMP ER susp/XR ODT pearls
use ≥6 y/o
Dose conversion NOT 1:1
food delays time to serum peak
Conversion: AMP XR > ODT/SUSP
5>3.1
10>6.3
15>9.4
20>12.5
25>15.7
30>18.8
mixed AMP salt ER pearls
Mydayis
≥13 y/o
12.5mg QAM
MDD adult: 50mg
MDD adoles: 25mg
Can’t convert 1:1 with other AMP
TRIPLE TIME release beads - reduce wear off
* IR bead + DR bead 1+ DR bead 2
Compared to ER/IR combo, does not have dip mid-day
AMP IR pearls
AT LEAST BID
preferred for < 5 y/o
Afternoon dose not to be given <6 hrs before bedtime
norepinephrine reuptake inhibitors MOA
inhibit pre-synaptic reuptake of norepinephrine (like MPH but no DA)
NE reuptake inhibitor DDI
avoid duplicate therapy
avoid additive QTc prolongation (APS/TCAs)
* Atomoxetine elevation w/ paroxetine/fluoxetine/bupropion
* Viloxazine (strong CYP1A2 inhibit, weak CYP2D6/3A4)
Norepinephrine reuptake inhibitor efficacy
not as good as stimulants
safe /effective in children/teenager/adult
onset takes 1-2 weeks
full benefit: not seen for 6-8 weeeks
behavior could worsen initially
Norepinephrine reuptake inhibitor ADR
Upset stomach
Psych
Cardiovascular QTC (more so than stimulants)
Avoid TCA, APS
Fatigue, sedation ,dizziness
* liver tox w/ long term atomoxetine
* renal dosing for viloxazine
What non-stimulant has BBW for new-onset suicidality?
Norepinephrine Reuptake Inhibitors
* Atomoxetine (Strattera)
* Viloxazine ER (Qelbree)
Viloxazine DDIs
ADs
*SSRI: dulox,fluox,parox
* SNRI: venlafaxine
* TCAs
APS
* ariprazole
* asenapine
* risperidone
* chlorpromaz,cloza, olanza
* perphenazine, thoridazine
Benzos
Opiates
* buprenorphine, hydrocodone, methadone, oxycodone
(strong CYP1A2 inhibit, weak CYP2D5/3A4)
alpha adrenergic receptor agonist MOA
Increase blood flow to prefrontal cortex
Enhance working memory/executive functioning
Inhibits NE release
alpha adrenergic receptor agonist efficacy
Not as effective as stimulants for monotherapy
onset of effect 1-2 weeks
alpha adrenergic receptor agonist ADR
sedation/dizziness
hypotension
constipation
heart block
which medications time to peak is delayed by high fat meals?
MPH
AMP
ER alpha adrenergic RA
non stimulant FDA approved dosing
QD-BID
* Atomoxetine MDD 40mg (5-20 BID)
* Clonidine ER MDD 0.4mg (0.1 QHS or BID)
QD only
* Vioxazine ER MDD 400-600 (≤17/adult; 100-600 QD)
* Guanfacine ER MDD 7 mg (1-4 QD)
Bupropion for ADHD
off label: 50-300mg/day
weak DA/NE reuptake inhibitor (like MPH)
benefit: adolescent w/ ADHD + depression; also adult..
bupropion ADR
less appetite supression/weight loss compared to stimulants
causes seizures (MPH better for seizures)
avoid in AUD/eating disorders
TCAs for ADHD
imipra: 50-150/day
Desipra: MDD 300
Nortriptyline: MDD 300
up to 4 weeks to see max effect
TCA ADR
sedation/dizzy
constipation
heart block
rapid heart beat
weight gain
overdose toxicity - suicide risk bad
Lithium/AEDs in ADHD
for aggression, explosive behavior, impulsivity
childhood onset BP or combined ADHD BP disorder
APS for ADHD
FGA: chlorpromazine/haloperidol
* hyper/impulse
* >cause EPS (BAD- permanent tardive dyskinesia!!)
SGA: risper/olanz/quet/zipras/aripip
* severe agression, comorbid conduct/bp disorder
* >metabolic syndrome risks
Preferred agents for ADHD in active SUD
atomoxetine
alpha agonist
bupropion
T/F: ADHD is a risk factor for development of SUD, and stimulant use does not affect risk of subsequent SUD
True
treating ADHD can reduce development of SUD
Starting treatment early for ODD/conduct disorder w/ ADHD with stimulants is indicated
helps avoid APS use later
reduce need for use of higher doses
Bupropion dosing in prepubertal children
BID dosing optimal, even in SR forms
metabolized faster
Atomoxetine dosing in children
BID preferred for tolerability
Which stimulant is less likely to have drug interactions?
MPH forms
Gender difference in bioavailability of MPH
males have increased F
Evaluating ADHD treatment
baseline sx/complaints
height/weight/eat/sleep baseline / Q3month
6 weeks at max tolerated dose is considered an adequate trial for which drugs?
Atomoxetine
Viloxazine
Bupropion
1-2 months is considered an adequate trial for which drugs?
Guanfacine
Clonidine
+monitor BP and pulse!
EKG not mandatory but often done
Managing reduced appetite d/t stimulant
eat high calorie meal when med is low (breakfast/HS)
Cyproheptadine at bedtime
Managing insomnia d/t stimulant
Give earlier in day /sleep hygiene
Lower last dose of day
Add sedating agent
* Clonidine»_space; guanfacine
* Melatonin (avoid if pre-puberty)
* Cyproheptadine
Try patch (effect wear off 1-3 hr)
IF RECENT ONSET: wait and watch, stimulants can help improve sleep cycle
Managing rebound symptoms d/t stimulants
trial long acting stimualnt
or
* Atomoxetine
* Antidepressant
Managing jitteriness/irritability d/t stimulants
Assess comorbid condition
Reduce dose
+/- mood stabilizer/atypical APS
