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2/18/2015

Outline

Diagnosing ADHD
Treatment Recommendations
Psychopharmacological Interventions
Stimulants

PSYCHOPHARMACOLOGICAL
TREATMENT OF ADHD AND
COMMON CO-MORBID DISORDERS

and Non-Stimulants

Treatment Strategies
Case Studies

Molly Butler, PMHNP-BC


Assistant Professor in Psychiatry

DSM Definition
Diagnosing ADHD

Inattentive Symptoms

Fails to give close attention to details or makes careless mistakes


Difficulty sustaining attention in tasks or play activities
Doesnt seem to listen when spoken to directly
Doesnt follow through on instructions and fails to complete tasks
Difficulty organizing
Avoids, dislikes or reluctant to engage in tasks that require
sustained mental effort
Loses things
Easily distracted
Forgetful

18 official symptoms
6/9 symptoms of inattentiveness or hyperactivity/impulsivity for
under 17 yo, only 5 in 17yo and older
Lasting at least 6 months
Maladaptive and exceeding norm for age
Begins prior to age 12
Causes clinically significant impairment in two or more settings
Not better accounted for by another disorder

Hyperactive/Impulsive Symptoms
Hyperactivity

Fidgets
Leaves seat when expected
to remain seated
Runs or climbs excessively
Difficulty playing or
engaging in leisure activities
quietly
Often on the go or acts as
if driven by a motor
Talks excessively

Impulsivity

Blurts our answers before


questions have been
completed
Has difficulty waiting turn
Interrupts or intrudes on
others

2/18/2015

Whats New in DSM-V

Rule Out Organic Causes

Autism Spectrum Disorder is not in exclusion criteria


Specifiers:
Severity: mild, moderate, severe
Presentations: predominately inattentive,
hyperactive/ impulsive or combined type
Broader areas of defined impairment
Developmentally appropriate descriptions

Differential Diagnosis

Depression

Anxiety Disorders (PTSD)

Bipolar Disorder

Autism Spectrum Disorder

ODD/ CD

Substance Use

Intellectual Disability

Speech and/or language disorder

Sudden life changes (divorce, death, move)

Typical development

Differential: Symptoms Specific to Anxiety

Phobias
Worries
Stress induced onset
Obsessions
Compulsions
Perfectionism
Somatic complaints
Posttraumatic play

Hyperthyroidism
Seizures
Lead toxicity
Food or food additive sensitivity
Sleep apnea
Substance abuse

Differential: Symptoms Specific to Depression

Depressed mood
Anorexia/ Weight loss
SI
Excessive Guilt
Psychomotor retardation
Mutism
Fatigue

Differential: Symptoms Specific to Bipolar


Disorder

Positive family history

Prolonged rages/ explosive irritability

Episodic

Euphoria- giddy or silly

Grandiosity

Risky acts without concern for safety

Decreased need for sleep

Pressured speech

Racing thoughts

Nearly

So

continuous need for 1 or more less hours per night than avg child without feeling tired

much or so fast they cant be understood or interrupted

Unintelligible,

rapid changes in thought pattern, flight of ideas, sentence fragments

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Differential: Symptoms Specific to Autism


Spectrum Disorder

Impaired nonverbal and verbal communication


Restricted Interests
Stereotyped/ repetitive movements
Inflexible adherence to routine/ rituals
Lack of:

Treatment

Fantasy

play
relatedness
Imaginative play
Social

Treatment Guidelines

NIMH multimodal treatment study of ADHD (MTA Cooperative


Group 1999, 2004)
children ages 7-9 with ADHD treated for 14 months
1) Monthly medication management with stimulant by specialist only
2) Behavioral management only (35 group sessions, therapist visited school
multiple times to work with staff, summer camp)
3) Combined group: meds plus behavioral management
4) Routine community care/ treatment as usual (TAU)
-PCP visits 1-2 times / year

Follow-Up to MTA

579

Superiority persisted for med and combination


treatment over behavioral management and TAU

Effect size was 50% smaller after 24 months

Med only groups dosages were significantly higher


than combination at 24 months

RESULTS: Medication only and combined groups were superior


to behavioral therapy alone and routine community care

Neurochemical Factors
Psychopharmacological
Interventions

Dopamine

Verbal fluency
Serial learning
Vigilance for executive
functioning
Sustaining and focusing
attention
Prioritizing behavior
Modulating behavior based
on social cues

Norepinephrine

Sustaining focus and


attention
Mediating energy levels
Motivation
Interest

2/18/2015

How Medications Treat Symptoms

Whats out there?

19

Increase in norepinephrine
increases strength of signals to the prefrontal
cortex
Increase in dopamine
increase in saliency, decreases noise from
extraneous stimuli

Stimulants

Non-Stimulants

Methylphenidates

Atomoxetine

Amphetamines

Alpha-2

(Strattera)
Agonists
Bupropion (Wellbutrin)
TCAs
Modafinil (Provigil)

Stimulants

Stimulants

Compared to other pharm options:

In RCTs, effect sizes for stimulant treatment of ADHD are usually


large for teacher ratings (0.8) and for parent ratings (0.5)
70% of children will respond to 1st trial
90% will respond to 1st or 2nd trial
Compared to placebo, stimulants:

Stimulant Medications
Methylphenidates

Methylphenidate

Ritalin

Methylin

Focalin

Ritalin SR

Amphetamines

Amphetamine/ dextroamphetamine

Adderall

Dexedrine

Dexedrine Spansules

Metadate ER

Dextro Stat

Methylin SR

Adderall XR

Ritalin LA

Vyvanse

Metdate CD

Focalin XR

Daytrana

Quillivant XR

Concerta

most studied, commonly used and effective


first line agents

Reduce hyperactivity and disruptive behavior


Improve parent-child interaction
Improve problem solving with peers
Reduce aggressive and antisocial behavior

How stimulants work

d,l- methylphenidate and d-amphetamine


Release

DA from presynaptic DA terminals


DA transporter (so blocks reuptake)
May reverse dopamine out of nerve terminal
Block

l-amphetamine
Similar

effect on both DA and NE

2/18/2015

Immediate Release Methylphenidate

Immediate release tablets


Ritalin,

Longer Acting Methylphenidate


Sustained release, long acting capsules, tablet or
liquid and transdermal patch
All methylphenidate BUT differ in number, rate and
shape of methylphenidate pulses into blood stream

Ritalin, D,L-Methylphenidate, Methylin

In quick, out quick:


effects in 30 minutes
Peak plasma levels in 90 minutes
Half-life 3 hours
3-5 hour duration
TID dosing

D,L-Methylphenidate, Methylin and Focalin

Behavioral

IR Methylphenidate Dosing

Focalin

older sustained release tablets


Ritalin SR, Metadate ER, Methylin SR
FDA approved ages 6-15
Immediate release tablet coated with wax matrix
Slower onset, lower serum concentrations
Peak in 5 hours
6-8 hours duration
Rarely used:

Sustained Release Capsules


Ritalin

Ritalin LA

LA, Metadate CD, Focalin XR

inside capsule contain half dose as immediate


release and half as delayed release
Mimics total dose given in immediate form about 4
hours apart

BID
Often need immediate release in morning to compensate

Long Acting Dosing

Ritalin LA and Focalin XR


Beads

Initiating treatment in young or small children


Appetite disruption with longer acting formulas
Adjunctive to longer acting formulas in am or afternoon

Methylphenidate, Single Pulse, Sustained Release

Start 2.5 mg
Increase q 7 days
Max: 20 mg total daily dose

Most common uses in my practice:

Long Acting Methylphenidate Capsules

Typically start 5 mg q am for children and 10 for adults


May increase dose q 3 days- 1 week
Add noon and afternoon doses first
Max dose: 20mg TID (60 mg total)

> 5 hours duration


Start 10 mg q am
May increase in weekly increments of 10 mg
Max 60 mg daily

Focalin XR

Duration 12-16 hours


Peaks at 1-2 and 6-7 hours
Start 5 mg po q am
Increase by 5 mg q week
Max 40 mg daily
After first peak 45% higher in women

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Metadate CD
Ages

6-15
as immediate release and 70% delayed release
Peaks 1-2 and 4-5
6-8 hours duration
Start: 10 mg po q am
Max: 60 mg po q am

Methylphenidate ER (Concerta)

Wont take a pill?

Methylin Chewable Tabs or Oral Solution


Comparable

to immediate release

Apply

in morning and take off 9 hours later


symptom reduction in first 2 hours
levels peak at 7-9 hours
Duration is 11.5 hours
Start with 10 mg/9 hr patch, may increase to next size patch q7 days;
Max: 30 mg/9 hr patch q day
Produces higher plasma levels than dose equivalents of other preparations
Tics more common and mild skin reactions are common
No

Plasma

Adderall, Dextrostat generic, Dexedrine


only

Produces ascending serum concentration


Similar to TID immediate release dosing with less variation
Start 18 mg po q am
May increase by 18 mg q week
Ages 6-12: max is 54 mg daily
13 and up: max is 72 mg daily
Disadvantage: may not be as effective in am as dual pumps in early
morning
Also approved for comorbid ODD and LD

Quillivant XR
methylphenidate ER oral solution
ages 6 and older
initial dose: 20 mg once a day
max dose: 60 mg once a day
may increase daily dose by 10-20 mg at weekly
intervals

Long-Acting Amphetamine

Adderall XR capsules (d, l-amphetamine)

medication with FDA approval down to age 3

4-6 hour duration


Plasma levels peak at 3 hours
Start 5 q am
Max 40 mg daily in split doses q 4-6 hours
Titration and clinical indication same as immediate
release forms of Methylphenidate

Tablet coated with immediate release methylphenidate


Osmotic pump releases rest of drug over 10-12 hours

Wont take a pill?

Daytrana Transdermal Patch

IR Amphetamines

Complex-release formulation

30%

Dual pulse with 1/2 immediate- and extended- release beads (just
like Ritalin LA and Focalin XR)
6-8 hours duration
Peak in 7 hours
Start 5 or 10 mg q am
Increase by 5-10 mg/day at weekly intervals as needed
Max typically 30 mg daily

Dexedrine Spansules (d- amphetamine)

Peaks in 4 hours
6-8 hours duration
Max 60 mg po q am

2/18/2015

lisdexamfetamine dimesylate (Vyvanse)

Prodrug of Dextroamphetamine

After oral administration it is rapidly absorbed in GI tract and


converted to active form, dextroamphetamine
Reduces risk for abuse

Ages 6-12, adults


Can be swallowed whole or opened up and mixed with water,
ice cream, applesauce or yogurt
Full 12 hour duration
More steady levels
Start 30 mg
but available in 20 mg capsule
Increase by 10-20 mg q week
Max: 70 mg daily

Stimulant Side Effects


Common

Decreased appetite and weight loss


Slowed growth rate (poorly documented)
Headache
Abdominal pain
Delayed sleep onset
New onset tics
Rebound crankiness and tearfulness
(immediate release)
Overstimulation
Nervousness
Picking at skin/ nail biting
Behavioral changes

Sudden death

Adverse cardiac events

Angina

Tachycardia

Palpitations

HTN

Tactile and visual hallucinations

Seizures

Activation of hypomania or mania

Take with food

Appetite suppression
Absorption and bioavailability may increase after meal

Immediate release

Capsules

Hx of heart defects or heart disease


Reports of murmur, syncope, chest pain, HTN or arrhythmias
Family hx of heart disease < 40 years old
Rates of unexpected sudden death on stimulants 0.19-0.5 in 100,000 patientyears and 1.3- 1.6 in 100,000 patient-years in general population

Caution in adults with preexisting heart conditions and HTN


Use with caution in:
patients or patients with family members with history of SUDs
patients with psychotic or bipolar disorders
patients with tics or Tourettes

Height/ Weight
BP
HR
Rating Scales

Stimulant Nonresponders

Can crush or break in half

Pt factors:
Is

it really ADHD?
there a comorbid diagnosis?
Are side effects interfering w response?
Is the patient compliant?
Is

But may need to increase with growth

Actually a protective factor for SUDs

Irritability
Aggression
Depressed mood

May have greater effect on behavior than attention sxs


If no improvement in target symptoms when dose is increased, drop back down
Wont cause addiction in those with ADHD

Baseline ECG/ echo and collaboration with cardiologist or PCP

Rare but Serious

If causes or increases nail biting, chewing or picking at skin consider baseline


obsessive/ anxiety features
If causes aggression and irritability consider comorbid process
Little evidence of tolerance to stimulant effect

Sudden death associated with cardiac abnormalities or other serious


heart problems

Monitoring patients on stimulants

Stimulant Clinical Pearls

Standard Warning on Stimulants

Medication factors:
Is

patient over- or underdosed?


there a time of day when med is not effective?
Are drug interactions effecting the response?
Is

Can open up and sprinkle

2/18/2015

Stimulant Nonresponders

Family Factors:

Nonstimulants

Are

there increased family stressors that contribute to


diminished stimulant tx response?
Is there a parent with undiagnosed ADHD or other
psychiatric illness adding to family stress?
Do care givers disagree on giving patient the med?

Nonstimulants

Atomoxetine, Clonidine, Guanfacine, Buproprion, TCAs and


Modafinil
Typically used when:

Inadequate response to stimulants

Monotherapy
Adjunct treatment

Unable to tolerate stimulants


Tic disorder
Patient or family history of SUDs
Caregiver preference
Comorbid disorders

Atomoxetine (Strattera)

Atomoxetine (Strattera)

Dosing:

Atomoxetine: Adverse Events

Children < 70 kg: start 0.5 mg/kg/day; after 3 days


increase to 1.2mg/kg/day. Max: 1.4 mg/kg/day or 100 mg
daily, whichever is less
Adults and children >70 kg: start 40 mg; after 3 days
increase to 80. May increase to max of 100 if needed after
2-4 weeks

Drug interactions:
Not within 14 days of MAOIs
Decrease dose of atomoxetine with CYP450 2D6 inhibitors
(fluoxetine and paroxetine)
Co-administration with albuterol may increase HR and BP

First drug approved for treatment of ADHD Approved


for ages 6+
Selective NE reuptake blocker causes increase in NE and
DA levels in prefrontal cortex
Peak plasma concentrations 1 hour without food and 3
hours with food
Half-life 5 hours but duration of action is much longer
than half-life so may dose once daily
Hepatic metabolism in cytochrome P4502D6

2 FDA warnings:

Black Box Warning for suicidality

Warning for liver injury

September 2005- Eli Lilly study- 5 / 1,800 spontaneously reported


suicidal ideation compared to 0 reports in placebo group
December 2004, reports of severe liver injury and jaundice in two patients
d/c in patients with jaundice, dark urine or lab findings of liver injury

Side effects:

GI upset and decreased appetite, drowsiness, increased HR (6-9


bpm), increased BP (2-4 mm Hg), insomnia, dizziness, anxiety,
irritability, dry mouth, dysmenorrhea, sweating, sexual dysfunction,
urinary hesitancy or retention

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Atomoxetine

What to do about SEs:

Alpha-2 Agonists: Guanfacine and Clonidine

Wait

dose
dose
Change medication
Split

and wt
BP and pulse

FDA-approved for use of HTN in adults since early 1970s


IR guanfacine and clonidine NOT FDA approved for ADHD
Grew in popularity for C/A psychiatry in 1990s

Monitor:
Ht

These meds stimulate postsynaptic receptors to increase the


strength of NE signals

Lower

Large number of alpha 2 adrenergic receptors in


prefrontal cortex that mediate ADHD sxs

Extended release versions approved by FDA for


monotherapy or stimulant augmentation

Alpha-2 Agonists: Clonidine and Guanfacine

Studies suggest benefits for behavioral target sxs of:

Aggression
Hyperactivity
Hyperarousal (anxiety/ PTSD)
Impulsivity
Sleep disturbance

Fewer benefits for attentional and cognitive sxs of ADHD


Additional uses:

Clonidine (Catapres) Data

Selective alpha-2A receptor agonist so has a


reduced SE profile compared to clonidine
Two open label trials with 23 children (Chappell et
al., 1995; Hunt et al. 1995):
No

efficacy or safety data available

Small controlled study by Hunt and Colleagues in 1985:

Only 10 children
Results: reduction in hyperactivity and aggression

Improvements averaged 22.9% on parent ratings in 5 published


studies on ADHD
Conner and colleagues 2000:

Adjunct therapy in ADHD


Treatment of rebound symptoms with stimulants
Comorbid tic disorder
ADHD and/or Aggression with CD
ADHD sxs in Autism Spectrum Disorder or Fragile X

Guanfacine (Tenex) Data

Clonidine Hydrochloride extended Release (Kapvay)


Guanfacine XR (Intuniv)

Pilot study comparing methylphenidate, clonidine and the


combination in 24 children with ADHD and either ODD or CD
All groups improved
Clonidine alone effect size of 0.56 (moderate effect size) in ADHD
sxs in children with comorbid conduct disorders, developmental
delay and tic disorders

Short Acting Alpha-2 Agonists

Dosing:

Clonidine (Catapres)

0.1 mg strength tablet


Start tab at bedtime
May increase by 0.05 mg q 4-6 days
Max typically 0.2- 0.3 mg total daily dosing
QID dosing for optimal benefit

Guanfacine (Tenex)

1 mg strength
Start tab at bedtime
May increase by 0.5 mg q 4-6 days
Max typically 3 mg total daily dosing
Dose TID
less sedating than clonidine

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Guanfacine XR (Intuniv)

FDA approved in 2009 for tx of ADHD ages 6-17


2 clinical trials
N=

345/324
weeks
Double-blind, placebo-controlled, parallel-group, fixed
dose design
Increased by 1 mg/week
No patients under 55 lbs

Guanfacine XR (Intuniv) Clinical Trials

8/9

ADHD sxs evaluated weekly with ADHD Rating Scale-IV


Mean reductions in ADHD-RS at endpoint were statistically sig
greater for intuniv
Placebo adjusted changes from baseline were statistically sig
for all dosages
Improvements seen at 0.05-0.8mg/kg/day
Additional benefit at 0.12mg/kg/day if tolerated
No differences in gender response
Most effective in 6-12 yo

Guanfacine XR (Intuniv)

Dont substitute for IR guanfacine on mg-mg basis


d/c

Clonidine HCL Extended Release (Kapvay)

Clonidine HCL Extended Release (Kapvay)

IR then start intuniv

Start 1mg once daily and increase by no more than


1 mg/day/week
Max dosage: 4 mg/day
Should be slowly tapered (by 1 mg q 3-7 days) due
to risk of rebound hypertension and tachycardia
Should re-titrate if miss two consecutive doses

Maintenance past 5 weeks not yet evaluated


Start 0.1mg and increase weekly as needed to 0.4
mg daily
BID dosing

Only 25% were 13-17


Fixed doses may have been too low (avg was 0.01-0.04 mg/kg)

Approved 2010 for tx of ADHD monotherapy and


was first to be approved for adjunctive therapy with
a stimulant
Two phase III trials which demonstrated improvements
in core sxs at 5 weeks for ages 6-17
SEs (incident >5% and 2x placebo) included:
somnolence,

fatigue, upper respiratory tract infection, irritability, sore


throat, insomnia, nightmares, emotional disorder, constipation, nasal
congestion, increased body temperature, drug mouth and ear pain

Alpha-2 Agonists in General

Side Effects:
sedation,

dizziness, orthostatic hypotension, dry mouth,


bradycardia, irritability, sleep disturbance, syncope

Caution:
Documented

sudden unexpected deaths in children


taking clonidine
Rebound HYPERtension associated with missed doses
Rare disinhibition

Monitoring
BP,

pulse

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Buproprion (Wellbutrin)

NDRI (Norepinephrine Dopamine Reuptake Inhibitor)


antidepressant
Preparations: Wellbutrin SR/XL, Budeprion, Zyban and
Alplenzin
Has been reported to be effective for ADHD symptoms in
some placebo-controlled trials (Casat et al., 1989, Clay et
al., 1988, Simeon et al., 1986)
Conners et al., 1986: multisite, DB, placebo-controlled trial.
Teachers reported improvement in ADHD symptoms but
parents did not
Not first line

Tricyclic Antidepressants (TCAs)

Not Approved for tx of ADHD d/t potentially serious CV events


Most are NE reuptake inhibitors
Imipramine (Tofranil)

Some studies have found comparable effects but more dropouts with IMI vs
Methylphenidate (Rapoport et al., 1974; Werry et al., 1980)

300-450 mg/ day immediate release


OR
300 mg /day SR

Decreased seizure threshold


Rare induction of mania
Dry mouth, constipation, weight loss, anorexia
Insomnia, dizziness, HA, agitation, tremor

Modafinil (Provigil)

MOA not fully understood


Alters balance of GABA and glutamate

Biederman and Colleagues, 2005:

Dosing: 2 mg/kg/day max 5 mg/kg/day (antidepressant dose)


TCA SEs: cardiac tachyarrhythmias, drowsiness, anticholenergic SEs and
seizures/ EEG changes
Monitoring:

Non-stimulant w/o cardiovascular effects indicated for narcolepsy

SR form in C/A is metabolized more rapidly than adults- dose BID.


No info on XL and Alplenzin form in C/A
Contraindicated: seizure DO (risk is dose dependent) and eating DO
Side Effects:

SEs including sedation


Tolerance to therapeutic effects in 6-10 weeks

ECG at baseline and at stable dose


Draw levels
Possible drug interactions

FDA Black Box Warning for suicidality


Dosing:

Superior to placebo but no head to head studies with methylphenidate

65

Nortriptyline (Pamelor)

Buproprion (Wellbutrin)

Large RCT, DB, PC study


425 mg daily
Improvement in ADHD core sxs at home and school

Equivalent to 6 cups of coffee (600 mg caffeine) on alertness and


performance tests in sleep deprived healthy adults (Wesensten et al.,
2002)
SEs: insomnia, HA, decreased appetite
Manufacturer withdrew application for ADHD indication in children
d/t report of Stevens-Johnson Syndrome and visual hallucinations

FDA Approved Drugs for Adult


ADHD

Stimulants
Adderall XR
Vyvanse
Quillivant XR
Focalin XR
Concerta
Non-Stimulant
Strattera

Treatment Strategies

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2/18/2015

How do we decide what to use?

Practice Parameters recommend oral stimulants as first line:

AACAP practice parameters for ADHD (Plizka and AACAP Work Group
on Quality Issues 2007)
An international consensus statement (Kuthcher et al., 2004)
American Academy of Pediatrics (2001)
The Texas Childrens Medication Algorithm Project: Revision of the
Algorithm for Phamacotherapy of ADHD (Plizka et al., 2006)

Stage 0:

Diagnostic assessment
Non medication treatment alternatives

Initial insomnia due to stimulant effect or ADHD sxs:

Stage 4:

Stage 5:

Change in formulations (immediate to long acting) not considered stage change


Proceed to stage 3 when one Methylphenidate and one Amphetamine have been used

Stimulant not used in stage 1

Stage 3:

Exogenous Melatonin

Methylphenidate or Amphetamine

Atomoxetine

Bupropion or TCA

Agent not used in stage 4

Adjunctive Therapy for Initial Insomnia Cont


Antidepressants

Alpha-2 agonists

Clondine up to 0.2 mg q hs

Tenex up to 2 mg q hs

with sedation as major SE

Serotonin 2 reuptake inhibitor


25-100 mg q hs
10% risk of priapism

Partial response

Breakthrough symptoms

Mirtazapine (Remeron)

Alpha 2 agonist and SNRI


7.5- 30 mg q hs
Low doses= most sedating
Increased appetite and wt gain

Typically an interrupted and not restful sleep

Additional Indications for Adjunctive


Pharmacotherapies

Trazodone (Desyrel)

Benadryl 25-50 mg
Hydroxyzine (Vistaril)
Anticholinergic SEs

Alpha 2 agonist (clonidine or guanfacine)

OTC
Natural hormone that regulates circadian rhythms
As a drug can synchronize circadian clock to environmental cycle
1.5-9 mg at bedtime

Antihistamine

Stage 6:

Anxiety
MDD
Tic Disorder
Aggression

When to Use Adjunctive Pharmacotherapy

Stage 2:

Stage 1:

for ADHD with no significant comorbid


disorder and with comorbid:

Start with atomoxetine when indicated


Practice guidelines DO NOT require a treatment failure or adverse event
before allowing trial of another agent

Algorithm for ADHD with No Comorbid Condition

Algorithms

AACAP practice parameters say to start with long acting formulation


of stimulant except with small or young child when long acting is not
available in low- enough dose, then use immediate release
formulation

The Texas Childrens Medication Algorithm Project: Revision of the


Algorithm for Phamacotherapy of ADHD (Plizka et al., 2006)

Add alpha 2 agonist or atomoxetine to stimulant


Add am or afternoon immediate release formulation to long
acting formulation

Rebound Symptoms

Irritability, whining, crankiness, tearfulness


Typically when stimulant wears off in afternoon or evening

alpha 2 agonists
another dose of stimulant

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Stimulants + Alpha 2 Agonists

Frequently used as adjunct therapies


Kapvay and Intuniv both have FDA approval for adjunctive therapy
4 reported deaths of children on methylphenidate and clonidine IR

16 week MC, DB trial


122 children with ADHD
4 groups: Clonidine, methylphenidate, both or placebo
Clonidine: 0.6 mg/ day
Methylphenidate: 60 mg/day
Monitored ECGs and vital signs
More incidents of bradycardia in children on clonidine (17.5% versus 3.4%)
No other group differences in ECG or CV outcomes
No suggestion of interaction between clonidine and methylphenidate on CV
outcomes

2/3 of children with ADHD also meet criteria for other psychiatric
disorders
50% have ODD or CD
50% have learning disorders
25-30% have an anxiety disorders
2% have Tourettes

Target sxs
SEs
Taking as prescribed
Missed doses

What is causing the most impairment?


Use Texas Childrens Medication Algorithms for
ADHD with comorbid disorders
Anxiety
MDD

Much higher with ADHD than random population sample or with other
disorders

Tic

disoder

aggression

10-30% of children develop depression


Up to 20% may have bipolar do

Other disorders increase the impairment associated with ADHD

Teacher input at least twice per school year


Weekly contact with initial dose adjustments then
monthly for first few months then less frequent if
stable
Annual discontinuation trial (usually summer)

Treatment of ADHD with Comorbid Disorders

Increased risk for mood disorders

Monitor by direct contact, phone or e-mail

All had additional risk factors

Real World: ADHD Rarely Seen Without Comorbid


Disorders

Daviss and Colleagues, 2008:

Managing a Client in the Ideal World

http://www.dshs.state.tx.us/mhprograms/adhdpage.
shtm

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Case Study #1

Case Studies

Ritalin

Case Study #2

Pt is a 15 yo fm seen for f/u of anxiety and depression. She is seen


with and without mom today.
Current Meds:
Zoloft 200 mg
Anxiety sxs are now well managed on current med regimen. Now, pt
and mom report difficulty focusing, inability to sit down and complete
work and distractability. Pt reports that she wants to do her work but
she can't. Her grades have been dropping significantly due to
incomplete work and lack of organization. She also reports sad mood
and passive SI without plan or intent. She denies current SI/HI and
recent SIB. She reports low energy and hypersomnia (>10 hours
nightly). She denies use of drugs or ETOH and most recent UDS was
negative. Mom gave provider several NICHQ Vanderbilt Assessment
Scales completed by parents and teachers. One teacher and both
parents were elevated for inattentive ADHD sxs.

Pt is a 9 y/o boy seen with GM for review of ADHD and


conduct disorder
Current Meds:
10 mg q am and with lunch.

He is now in 4th grade where they go to school for an extra


45 mins daily (8-3:45). He does well most of the day but,
during last two classes he is having trouble with talking
excessively, not being prepared for class and not getting
classwork done. He is also not bringing home necessary
supplies for homework and is still working on it as late as 9pm
q night.
Tolerating Ritalin without SEs. No change in sleep or appetite.
No additional meds

Case Study #3

Pt is an 8 yo boy who presents with mom and PGM.


Current Meds:
Adderall XR 10 mg po q am
Family reports a favorable response to Adderall XR 10 mg which was
started 3 weeks ago. Mom reports that he is much more calm and that he
has been "wonderful". Teacher reported that his school work has
improved, behavior is good, no longer squirming or getting out of seat
and has had good manners. Family is concerned that pt is agitated,
hyper-emotional and angry in the late afternoon and early evenings when
medication is wearing off. Overall mood is "happy.
Some decrease in appetite but still eating well. No sleep disturbance. No
tics or additional SEs noted.

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2/18/2015

Case Study #4

Pt is an 11 yo ca f seen for f/u for ADHD and adjustment d/o r/t family discord,
neglect and variable involvement of bio-mom.
Current Meds:
Tenex 0.5 mg TID
Concerta 18 mg
Pt has been taking Concerta 18 mg X 2 weeks. GM reports that pt c/o chest pain,
agitation, nervousness, "not feeling like herself" and anger on Concerta. GM reports
that pt was given EKG by PCP due to c/o chest pain on Vyvanse and it was wnl. No
reports of syncope. Vital signs wnl.
She continues to be hyperactive, impulsive and defiant. This is problematic at home,
school and church. Current wt. 132 lbs, 60 kg
Past medication trials:
Vyvanse
Adderall XR
Concerta
Focalin XR
Pt c/o several SEs on all stimulants.

References
Barkley, Russell A (2000). Taking Charge of ADHD: The complete, authoritative guide for parents
(Revised ed.). New York: Guildord Press.
Barkley R, Murphey K (2005). Attention-Deficit Hyperactivity Disorder: A Clinical Workbook. New
York: Guliford Press. .
Findling, Robert L. (2008). Clinical Manuel of Child and Adolescent Psychopharmacology (4th ed.).
Arlington: American Psychiatric Publishing, Inc.
Green, Wayne H. (2007). Child and Adolescent Clinical Psychopharmacology. Philadelphia:
Lippincott, Williams and Wilkins.
Kolevzon A, Stewart D (2004). Psychiatry Pearls: The Pearls Series. United States: Hanley & Belfus,
Inc.
Lewis (2007). Lewiss Child and Adolescent Psychiatry: A Comprehensive Textbook (4th ed.).
Philadelphia: Lippincott, Williams and Wilkins.
Sadock B, Sadock V. (2003). Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry (9th ed.).
Philadelphia: Lippincott, Williams and Wilkins.
Stahl, Stephen M. (2000). Essential Psychopharmacology: Neuroscientific Basis and Practical
Applications (2nd ed.). Cambridge: Cambridge University Press. S
Stahl, Stephen M. (2008). Everything You Wanted to Know About ADHD But Forgot You Wanted to
Ask. Carlsbad, California: NEI Press.

The End

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