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