CHANGING CONCEPTS OF ADHD IN ADULTS
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Transcript CHANGING CONCEPTS OF ADHD IN ADULTS
Medications and
Psychosocial
Treatments for ADHD
Thomas E. Brown, PhD
Associate Director,
Yale Clinic for Attention and Related Disorders
Department of Psychiatry
Yale Medical School
In the Human Brain
100 billion neurons
each one linked to >1000 others
in complex sub-systems
that have to “talk to each other”
using low voltage electrical impulses
that have to jump across gaps
so fast that 12 can cross in 1/1000 sec.
The Jungle
Neuron
Synapse
Intertwined
neurons
Chemicals Jump the Gaps
Inside brain >50 different chemicals are
continuously made
every neuron system uses 1 of them
stored in little vesicles near tip of
neuron
when electrical impulse comes, minidots of that chemical are released,
cross the gap, fire next neuron, then
reload in fractions of a second
Message
Zips in
Releasing
transmitter
Message
Zips on
Reloading
transmitter
2 crucial chemicals:
(dopamine, noripinephrine)
control most of functions impaired in
ADHD
Brain of person with ADHD makes
these chemicals, as does everyone
else
but does not release & reload
effectively control messages often not
connecting
For 80% of those with ADHD
medications improve this problem.
How do ADHD Impairments of EF
Usually Respond to Medication?
This wide range of cognitive
impairments responds to
medication treatment in 70-90%
of cases in children, adolescents
and adults
Symptom improvement varies
from modest to very dramatic
Adverse effects are usually
transient, not significant
Safety of ADHD Medications
American Medical Assn. Report
“More than 170 studies involving >6,000
children using stimulant medications for
ADHD…up to 90% will respond to at
least 1 stimulant without major adverse
events if drug titration is done carefully “
Adverse effects from stimulants are
generally mild, short-lived, & responsive
to dosing or timing adjustments”
(Goldman, et. al., 1998, pp 1103-1104)
Substance Abuse
Associated With ADHD
Risk of developing SUD over lifetime is 52%
for adults with ADHD vs 27%
In ADHD, substance-use disorders onset
earlier, last longer, & remit more slowly
If ADHD is appropriately treated with
stimulant medications in childhood and
adolescence, risk of SUD reduced 84%
Wilens, Farone, Biederman, et al, Pediatrics, 2003)
ADHD: Targets of Pharmacotherapy
Core symptoms:
• Inattentive ± hyperactive, impulsive
Associated impairment:
• occupational failure, social and
academic deficits
Pattern of comorbid disorders:
• oppositional, antisocial, substance use,
mood and anxiety disorders
MTA Study of ADHD Tx
579 children (7-9 years)
ADHD Combined Type
14 months duration (10 yr f/u)
Six sites
MTA Groups
1. Med Mgmt: tailored dose design
TID dosing, monthly monitoring
2. Behav Tx: 8 wk summer prog, pt
training child tx, schl aide, tchr consults,
daily rpts.
3. Combined Med Mgmt + Behav Tx
4. Com Care: evals, 67% on meds, BID
MTA Results
1. Med Mgmnt, Comb Tx >Beh Tx,
ComCare
2. Combined Tx = Med Mgmt for ADHD
Sx
3. Comb Tx slightly better for assoc probs
4. Med Mgmt better than ComCare meds
MTA Study
“Excellent Response” to Tx
% of Ss scoring average of <1
(“just a little”) on SNAP-IV for
Inattn, Hyper/Impulsive, Opp/Defiant
25% Community Care
34% Behavioral Treatment only
56% Medication Mgmt only
68% Combination Tx
(Swanson, et. al., 2001)
Rates of Sudden Death in
population vs. on stimulants
SD rates in General Population (Berger et
al. Ped Clin N America, 2004)
• 0.6-6 / 100,000 children/ year
• 1
/ 1000 adults/year
Estimated SD rate on stimulants (based
on Rx data)
• 0. 25/ 100,000 people/ year (calculated based
on data)
• 0.50/ 100,000 people/ year (assuming 50%
underreporting)
(T.Wilens, 2006)
FDA Pediatric Advisory Committee 3/24/06
Reassessment by larger FDA Pediatric
Advisory 3/24/06
• No additional CV risk in
medically healthy kids
• risk with structural heart
defects approximates that in
child athletes
(T. Wilens, 2006)
FDA Advisory Committee 2/9/06
Recommendations
American Heart Association Guidelines (Gutgesell et al., Circulation; 1999; J
Am Acad Child Adoles Psych; 1999)
No need for ECG, Echo, Cardiac biopsy in routine cases
But if:
-- Family history of SD (<30 yrs of age)
• Hx of structural / congenital cardiac structural defects
• Syncope
• Chest pain
• Palpitations
• Hypertension
(T. Wilens, 2006)
Monitor during treatment
Patients’ Fears of Medications
for ADHD
Change personality “zombie”?
Slow growth? Start tics?
Lose appetite? Sleep?
Later drug or alcohol problems?
Dependence on meds for lifetime?
Being labeled, attribution problems?
Reactions of family, teachers, peers?
Controversial Treatments for ADHD
Dietary restrictions (food dyes, sugar)
Diet supplements: anti-oxidants, algae
optometric vision training
EEG neuro-feedback
No scientific evidence
for the safety
or effectiveness of these treatments for ADHD,
but NIMH is doing study on neurofeedback
ADHD “miracle” duped thousands
Dore treatment claimed to help ppl with
dyslexia and ADHD by stimulating
cerebellum with exercises
40K ppl completed 12 mo program at
cost of $4970.
Journal article in Dyslexia praised Dore
(biased & flawed)
Clinics closed, company bankrupt,
many clients got no refund
A Chemical Problem
ADHD is fundamentally a chemical
problem
Most effective treatment is to
change the chemistry with
medication
Unless the problematic chemistry is
changed, other interventions are
not likely to be very effective
Attention Deficit
Hyperactivity Disorder
Pharmacologic Treatments
Approved by FDA for ADHD Not Approved by FDA for ADHD
Stimulants
Methylphenidate
Amphetamine compounds
Dextroamphetamine
Lisdexamfetamine
Antidepressants
Tricyclics
Bupropion
Antihypertensives
Clonidine
Guanfacine
Nonstimulant
Miscellaneous
Atomoxetine
Combined pharmacotherapy
Modafinil
Venlafaxine
Neuroleptics (only in severe cases with monitoring)
Adapted from Wilens TE, et al. Annu Rev Med. 2002;53:113-131. Greenhill LL. Childhood attention deficit
hyperactivity disorder: pharmacological treatments. In: Nathan PE, Gorman J, eds. Treatments That Work.
Philadelphia, Pa: Saunders; 1998:42-64.
Stimulant Medications
Amphetamine
- dextroamphetamine (Dexedrine): 4-6 hours
• d, l amphetamine (Adderall): 4-6 hours
• Extended release (Adderall-XR) 8-10 hours
• Lisdexamfetamine (Vyvance) 10-12 hours
Methylphenidate
• Ritalin: 4 hours
• Concerta: triphasic, 10-12 hours
• Metadate CD: biphasic, 8 hrs
• Focalin (d -isomer) 4 hours
• Focalin-XR 8 hours
• Ritalin-LA (biphasic) 6-8 hours
Medications for ADHD Syndrome
Demonstrated safe and effective
Often do not follow mg/kg
Effective dose not based on age, wt or
severity of sx
Require titration and monitoring to “fine
tune” to:
- individual sensitivity
- time frames for schedule and tasks
Time Frames and Rebound
If sustained feeling/acting
excessively:
• “wired” or racy
• irritable
Level of med in the bloodstream
• serious, loss of “sparkle”
during the time dose is active,
dose is probably too high
Active
If these effects occur
as med is wearing off,
problem is more likely
to be “rebound”, ie
dropping too fast.
Drop-off
Time
Ingestion
TE Brown, 2002
ADHD
Response to Stimulants
Meta-analysis of within-subject comparative trials
evaluating response to stimulant medications
40
Best
Response30
(Percent)
38%
36%
26%
20
10
0
Dextroamphetamine Methylphenidate
Equal response
to either
stimulant
R
OROS (methylphenidate HCI)-
Concerta
Capsule-Shaped Tablet
Orifice/Exit Port
Drug
Overcoat
Drug
Compartment #1
Rate
Controlled
Membrane
Drug
Compartment #2
Water
Water
Push
Compartment
Before Operation
During Operation
Metadate™ CD (methylphenidate)
Extended-Release Capsules for ADHD
Biphasic Release: Bead-Delivery System
d-MPH-XR
(Focalin XR™)
• 50% IR d-MPH beads
and 50% ER d-MPH
beads covered by
polymer overcoat
• Can be sprinkled
on food
Single isomer technology
• Composed of only the
d-MPH stereoisomer
(dexmethylphenidate)
Mean plasma
concentrations over
time
Mean Plasma Methylphenidate
Concentration (ng/mL)
SODASTM release system
•
20
Two peaksOROS
®
MPH 18 mg qd
MPH MR 20 mg qd
SODASTM MPH 40 mg qd
15
d-MPH-XR 20 mg qd
10
5
0
0
Source: Focalin XRTM [package insert], Novartis Pharmaceuticals Corporation.
4
8 12 16 20 24 28 32
Time (h)
Stimulant Dosing
Medication
Usual Dosing
Starting Dose
Maximum Dose*
Ritalin®
Focalin®
5 mg QD/BID
2.5 mg
2 mg/kg/day
1 mg/kg/day
TID (4 h)
BID (5-6h?)
Concerta®
MetadateCD®
Ritalin LA
Focalin XR
18 mg QD
20 mg QD
10 mg QD
5 mg QD
2 mg/kg/day
2 mg/kg/day
2 mg/kg/day
2 mg/kg/day
QD (12 h)
QD (6-8 h)
QD (6-8 h)
QD (8-10h?12)
Adderall®
AdderallXR®
Vyvanse
Dexedrine®
Dex Spansule
2.5 to 5 mg QD
5-10 mg
30 mg
2.5 to 5 mg QD
5 mg
1.0 mg/kg/d
1.0 mg/kg/d
30 to 70 qd
1.0 mg/kg/d
1.0 mg/kg/d
BID (6 h)
QD (12 h)
QD (13 hr)
BID/TID (4 h)
BID (6 h)
*Maximum dosing may exceed FDA approved dose limits.
Wilens, et al. Annu Rev Med. 2002;53:113-131; updated 2005.
Advantages of Extended-Release
Formulations of Stimulants
Provides sustained medication levels
throughout the day
Smoother: minimizes ups and downs during
day
No midday dose required, eliminating trips to
the school nurse, doses during workday
Reduces stigma
Enhances patient compliance
May reduce illicit diversion and abuse
Management Strategies for:
Severe Decrease
Headache/Stomachach
In appetite
e,
• Monitor weight
Irritability/Moodiness,
• Administer with or
or OCD Symptoms
after meals
• Decrease dose
• Give high-calorie
snacks
• Switch to another
stimulant
• Consider
medication
• Switch to 2nd line
holidays
agent
• Eat in reverse
Wilens & Spencer, 2000
Management Strategies for:
Delayed Sleep
Latency
Sleep
Hygiene/Bedtime
rituals
Change to shorter
acting stimulant
Consider adjunctive
treatment (e.g.,
clonidine)
Relaxation training
Irritability
Evaluate when it
occurs
• Peak (too high dose)
• Wear off (? rebound)
Change dose
Assess for comorbidity
Consider adjunctive
therapy
Wilens & Spencer, 2000
Non-Stimulant
options for ADHD
Specific noradrenergic agent approved for
ADHD
-Strattera (atomoxetine)
Antidepressants (not approved for ADHD)
-Wellbutrin (buproprion)
-Pamelor (nortriptyline)
-Norpramin (desipramine)
Alpha-2 Agonists (not for cognition) (Not Approved for
ADHD)
-Catapres (clonidine)
-Tenex (guanfacine)
Dosing of Atomoxetine in ADHD
PDR Recommendations (Not a controlled substance)
• Start ≈ 0.5 mg/kg/d
• Target 1.2 mg/kg/d
• Max of 1.4 mg/kg/d or 100 mg/d
Example: 8 year old
• Start 18 mg for 4-7 days in AM after food
• 25 mg for 4-7 days then increase to 40 mg
If already on stimulant, cross-taper, introduce ATMX then
reevaluate need for stimulant
Available in 10mg, 18mg, 25mg, 40mg, 60mg
Sprinkling not formally tested and may irritate GI tract
Full benefits often not seen Physician
until 4DesktoReference
6 weeks
of treatment!
. Monvale, NJ:Thompson PDR;2005.
®
Dosing of Atomoxetine in Adults
Initial: total daily dose of 40 mg increased
after ≥ 1 week to a target of ~80 mg
Administered either as:
• Single daily dose in the morning
• Evenly divided doses in the morning and late
afternoon/early evening (bid dosing in adult
trials)
After 2 to 4 additional weeks, dose may be
increased to a maximum of 100 mg daily
(patients without an optimal response)
Full benefits often not seen until 4 – 6
weeks of steady treatment!
Strattera® [package insert]. Indianapolis, Ind: Eli Lilly; 2003.
Comparative Study of ATX vs OROS
492 patients with ADHD (6-16 yrs)
randomized to ATX (0.8-1.8 mg/kg/d)
OROS (18-54 qd) or PBO for 6 wks
Response (≥40% sx improvement)
ATX: 45% OROS: 56% PBO: 24%
Of 70 Non-responders to OROS 43% +
Of 69 Non-responders to ATX 42% +
(Newcorn, Kratochvil, et al, 2008)
Types of non-pharmacological
treatments
1. Psychoeducation about ADHD and its
treatment to address prejudices/fears
2. Cognitive-behavioral treatments to modify
maladaptive attitudes
3. Remedial instruction/coaching to modify
deficits or maladaptive behaviors
Non-Pharmacological Treatments
are important to ADHD treatment
ADHD/ADD results from impairment
brain chemistry
and medication is most effective
treatment
BUT, medication
is not effective if not taken
cannot fully alleviate some symptoms
Some ADHD patients
do not take their ADHD medications
Because they:
have prejudices about the disorder
fear and don’t understand ADHD
meds
Primary Prejudice about ADHD
“It’s essentially a simple problem,
a matter of willpower”
because….
“It’s just being too hyper and not listening”
“Everyone with ADHD can pay attention
very well for certain specific activities”
Primary fears about ADHD medications
“This will make problems for me”
“make me too hyper or too slow”
“take away my personality”
“get me dependent or addicted”
Patient Education is needed about
medications
Need to be “fine-tuned” in
collaboration with each patient
Set patient expectations to collaborate
adjust med, dose or timing to individual
needs and body chemistry
prevent stimulant “rebound”
Need to report any side effects
Home Interventions
for ADD/LD School Problems
daily parental reading with child
daily parental help with organization/study
early computer training and use
supplementary audio or videos
remedial tutoring
avoid micro-managing homework for teens
protect non-academic strengths
Parent Training for Management of
ADHD Behavior Problems
positive attending
rewards for appropriate behavior
planned ignoring
transition management
target behaviors & point systems
use of “time out” & “response cost”
(Cunningham, 1998; Teeter, 1998)
Improving Interactions of ADHD Teens
and Their Parents
recognize aims & limits of parental
control
facilitate appropriate independence
seeking
maintain adequate structure &
supervision
establish & enforce “bottom line” rules
negotiate all “non-bottom line” issues
use consequences wisely to influence
focus on positives, practice forgiveness
School Accommodations
for ADD/LD
Daily check of assignments &
organization
preferential seating
reduced volume of work
weekly/daily progress reports
alternative test delivery (oral/written)
extended time for tests (as needed)
(S.Rief, 2005, C.Dendy, 2000)
Cognitive Behavioral Treatments for:
Defensive attitudes about self & others:
“Everyone expects too much from me.”
“I may seem smart, but I’m really stupid.”
“High goals just bring disappointment.”
“It’s not worth trying; the world is unfair.”
“I’m just destined to be a loser.”
These attitudes have cognitive & emotional aspects
Remedial instruction or Coaching for:
Skill deficiencies that persist
Study skills and academic deficits
Organization of ideas and stuff
Priority setting & time management
Budgeting income and spending
Monitoring self in conversations
Pills don’t teach skills.
Clinical Tips for Psychosocial Treatment
of Adult ADHD
(Ramsay & Rostain, 2005, 2007)
Assess patients’ “readiness for change”
(motivation and resources)
Provide psychoeducation about ADHD
Maintain an active therapeutic stance
and collaboration with patients
Pay attention to the quality of the
therapeutic relationship
Maintain focus on specific functional
problems faced by patients
Clinical Tips for Psychosocial Treatment
of Adult ADHD
(Ramsay & Rostain, 2005, 2007)
Implement cognitive modification and
foster resilient attitudes
Normalize trial-and-error nature of the
therapy process for adult ADHD
Encourage individualized coping
strategies for “living with ADHD”
Maintain ongoing case
conceptualization
Consider referrals for additional clinical
services (e.g., medications, coaching)
Cognitive Model of Psychotherapy
(Ramsay & Rostain, 2005, 2007)
• Based on cognitive model of
•
•
•
•
psychopathology
Time efficient
Structured, active
Collaborative problem-solving
Regular homework
Interventions to Provide
Therapy & Support
relevant articles, books and websites
support groups: CHADD, ADDA
on-site support: for patient, teachers
psychotherapy- individual, conjoint
parent support/training mgmnt skills
crisis intervention
“realistic hope” vs. “optimism”
Levels of Care for ADHD
tailor to pt & family needs
Comprehensive assessment for ADHD,
comorbid disorders, and context
Family Education re: ADHD and its tx
PE, “fine-tuning” of meds, monitoring
Parent support & behavior mgmnt
training
Accommodations/Interventions in
school
Psychotherapy: individual, family