ADHD

ADHD 3 main characteristics

ADHD 3 main characteristics

inattention, hyperactivity, impulsivity

comorbidities with ADHD

ODD, CD, tourettes, susbtance use disorder, learning disabilities, mood/anxiety disorders

inattentive subtype DSM IV

6+ of the following sx have persisted for 6mo to a degree that is maladaptive and inconsistent with development levels

• fails to give close attn to details or makes careless mistakes

• has difficulty sustaining attention in tasks or play activities

• does not seem to listen when spoken to directly

• does not follow instructions and fails to finish schoolwork, chores, duties

• has difficulty organizing tasks and activities

• avoids, dislikes or is reluctant to engage in tasks which require sustained mental effort

• loses items necessary for tasks or activities often

• is easily distracted

• is forgetful in daily activities

hyperactivity/impulsivity subtype ADHD DSM IV

6+ of the following sx have persisted for atleast 6mo to a degree that is maladaptive and inconsistent with development level

• fidgets with hands or feet or squirms in seat

• leaves seat in situations where remaining seated is expected

• runs about or climbs excessively in situations in which it is appropriate

• has difficulty playing or engaging in leisure activities quietly

• is often on the go or acts as if driven by a motor

• talks excessively

• blurts out answers before q’s have been completed

• difficulty waiting their turn

• interrupts or intrudes others

explain the time course of ADHD sx

preschool- hyperactive/impulsive

elementary school- inattention starts to become more prominent

adolescence- predominantly inattentive. impulsive behaviours. hyperactivity manifests more as fidgetiness or impatience

adult- inattentive sx predominate. impulsivity may remain problematic even when hyperactivity has diminished

med classes used in ADHD

stimulant, non stimulant, antidepressants, alpha 2 adrenergic agonists

Best evidence of ADHD treatment is what combo

behavioural and pharmacological Tx

moa stimulants (brief)

PFC is hypoactive. inhibitory networks are surpressed bc of low DA/NE

stimulants increase DA/NE by inhibiting reuptake pumps.

low dose stimulant effects

effects NE more than DA

causes less blasts of dopamine in mesolimbic tract= less abuse potential

methylphenidate moa

block NET and DAT (binds allosterically on external cell membraine)

Long acting methylphenidates

Concerta, Biphentin

Intermediate acting methylphenidates

ritalin SR

short acting methylphenidate

ritalin

long acting stimulant duration of action

10-12hr

intermediate acting stimulant duration of actin

6-8hr

short acting stimualnt duration of action

3-4hr

Which med is the best starting choice for pts age 5-18 + why

Methylphenidates- similar efficacy + better tolerability vs amphetamines

do amphetamines or methylphenidates exacerbate tics more

amphetamines

amphetamine MOA

block NET + DAT, unlike MPH is transported inside the neuron and blocks vesicular reuptake pumps which decrease DA/NE storage and increases intraneuronal dopamine and NE which then spills out into synaptic cleft via channels

long acting amphetamine ex

adderall xr, vyvanse

intermediate acting amphetamine ex

dexedrine spansules

short acting amphetamine ex

dexedrine tab

which med is first line in adults and why

amphetamines - slightly better efficacy, equal tolerability

lisdexamphetamine specific characteristics of metabolism/absorption

prodrug of dextroamphetamine

not active- undergoes enzymatic cleavage in intestinal wall to dextroamphetamine and lysine and is absorbed

onset of effect of vyvanse

2hr

atomoxetine moa

selective NRI (or NET inhibitor)

Why does atomoxetine have less abuse potential

does not increase DA or NE in the nucleus accumbens/mesolimbic tract because there are few NETs present there and therefore no abuse potential

duration of action of atomoxetine

24hr

onset of EFFECT of atomoxetine

2-4wks

bupropion moa

NDRI- increases NE and DA transmission in PFC by blocking NET. increases DA transmission in nucleus accumbens by blocking DAT

cons of bupropion

can cause and exacerbate tics

causes insomnia

dose related seizure risk

doesnt work as well or as fast as stimulants

who is it a good idea to use bupropion in

ADHD and comorbid depression

Alpha 2 agonists work on the _____ synaptic receptor

post

Alpha 2 agonist moa

potentiate the effect of NE in PFC

when are alpha 2 agonists used

monotx or adjunct to stimulants (for aggression, tics, comorbid ODD- dont work well in adults)

alternative in children/adolescents unresponsive or intolerant to stimulant meds

What sx do alpha 2 agonists work for

hyperactivity, impulsivity

differences in guanfacine and clonidine

guanfacine in selective for alpha 2A

guanfacine has longer DOA, dosed once daily

less ae in guanfacine like sedation bc its more selective

First line agents (CADDRA guidelines)

stimulants (MPH and DEX products)

atomoxetine?

second line agents (CADDRA guidelines)

intermediate and short acting stimulants

third line agents (CADDRA guidelines)

Antidepressants (desipramine, nortriptyline, imipramine, bupropion, venlafaxine)

post synaptic alpha 2 agonists

best suggested use for atomoxetine

poor response or tolerability to stimulants or co morbid substance abuse, anxiety, tics, psychosis

1st line management of ADHD for 4-5 yr olds

behavior tx alone, then stimulants if poor response

which meds can be sprinkled on soft food or diluted in water

adderall XR, dexedrine spansules, biphentin, foquest- sprinkle beads on apple sauce

vyvanse- open caps and dilute in water/OJ/yogurt- chew tabs aswell

Onset of effect for anti depressants/alpha 2 agonists

2-4wks

Benefits of long acting agents

once daily admin= less flux in serum conc

less rebound

improved adherence

avoid having to take meds at school

Cons of long acting agents

may affect evening appetite and sleep

some may still require IR product in afternoon to control evening Sx or in the morning to get faster onset of effect

Pro of short acting agents

offer dosage flexibility during Tx initiation

useful as an add on to longer acting agent (ex: to control evening sx, to provide faster morning onset of effect)

What to do if tics appear/worsen on stimulants

switch to MPH if on DEX- if on MPH: atomoxetine, imipramine is an option

Tx tics with risperidone or alpha agonist

D/c + rechallenge

meds to consider with someone with substance abuse

strattera, bupropion, vyvanse, concerta

longer acting may have lower abuse potential but avoid stimulants in pt with known or suspected substance abuse or drug diversion

meds to use with comorbid mood disorders or anxiety

atomoxotine or antidepressants (may adress both or be used as adjunct to stimulants)

meds to avoid with psychosis

stimulants, bupropion

meds to avoid with bipolar/anxiety

stimulants, atomoxetine

safer choices for pts with psychiatric/neurologic comorbidities

clonidine and guanfacine

undesirable effects with clonidine/guanfacine

tx emergent irritability, depression, nightmares

CV risk with ADHD meds

rare but serious CV events (SCD, MI, stroke, arrythmias, syncope, chest pain) have occured in users of stimulants, atmoxetine, MPH/clonidine combo

stimulants/atomoxetine are sympathomimetic agents and can cause small but significant increases in BP, HR and potentially increase risk for SCD

stimulant dosing tips

start low and increase weekly by the same amount until improvement or intolerable SE occur

weight based dosing not used

ritalin dose no later than 4pm

atomoxetine dosing tips

children weight based dosing

may be prescribed bid morning and late afternoon to improve tolerability

How to tell if Tx is working

document baseline Sx over 1/12 pre med period with goal to identify 3-6 target outcomes that are reliable and can be measured

collateral history from parents/teachers

rating scales aviailable

monitor for improvement in frequency and severity of core Sx (attention, hyperactivity, impulsivity)

other concerns like reading, social skills, academics may not improve

goal to alleviate sx and improve fxning at home/work/school- less disruptive, sit still, pay attn, etc

what to do if tx isnt working

confirm diagnosis, check adherence, alter dose/dose schedule, switch

how to manage insomnia

avoid giving stimulants too late in day

consider using shorter acting formulation

melatonin 3-6mg 30min-2hr at sunset

benzos, zopiclone in adults

how to manage rebound hyperactivity

use long acting stimulant or more frequent dosing of short acting, switch to non-stim like atomoxetine

how to manage appetite suppression and weight loss

take med with/after breakfast

high calorie meal closer to the end of day

switch to whole milk

prep nutritious snacks

encourage child to eat when hungry

high calorie drinks- breakfast drinks, boost

if weight loss >10% switch nonstim

growth suppression effects from stimulants

extent to which long term stim use results in height/weight deficits is unclear

1cm/yr for first 1-3yrs noted, overall potentially a 0.5-1inch deficit overall

dont do drug holiday

monitor with atomoxetine aswell

how to manage headaches

tx with mild analgesics (tylenol/nsaids)

usually dissapates when on stable dose for a few wks

atomoxetine specific ae

hepatoxicity (jaundice, LFTs 40x ULN)- rare case reports and recover with d/c drug

sexual dysfxn

increased suicidality

how long to tx adhd

no consensus- 1/3 of chidlrens sx get better in adulthood. medication may not be needed long term but many will benefit

how to assess if you still need adhd meds

gradual withdrawal when school is in season

how to d/c stimulants

stimulants used for >3mo should be tapered over 2-4wks

D isomer of amphetamine is more potent for…

DAT

L isomer of amphetamine is more potent for

NET