Transcript ADHD: WHAT’S HOT AND WHAT’S NOT School Health …

MEDICATION TREATMENT OF
ADHD
CSNO Conference
February 9, 2013
Thomas S. Jensen, MD
10505 Sorrento Valley Road, Suite 390
San Diego, CA 92121
619/225-2220
[email protected]
Stimulant Medications for ADHD
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Work by “stimulating” neurons in the brain that
utilize Dopamine and Norepinephrine as their
messengers.
Can be divided into two families that work in
slightly different ways in the brain.
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The Ritalin Family (Ritalin, Focalyn, Focalin XR
Ritalin SR, Concerta, Metadate, Daytrana Patch)
The Amphetamine Family (Adderall, Adderall XR,
Dexedrine, Dexedrine Spansule, Vyvanse).
Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved
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Stimulant Medications for ADHD
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Each of these two “Families” has longer acting
forms and shorter acting forms. The long
acting forms use one of four strategies to be
long acting:
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Imbed the drug in a waxy slow to digest matrix
Imbed the drug in beads that dissolve at different
times
Deliver the drug in an osmotic chamber
Deliver the drug by transdermal patch
Link the drug to a big molecule that must be cleaved
to enter the brain
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Stimulant Medications for ADHD
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We generally prefer the longer acting forms of
Stimulant medications so we can avoid giving
medications at school.
Some long acting forms are harder to abuse:
– Concerta is hard to crush and snort and it irritates
the nose severely.
– Adderall XR irritates the nose as well, but people
can snort it.
– Vyvanse is cleaved by an enzyme and there is only
so much enzyme present so that taking more does
not give you much of a high.
– But “where there is a will, there is a way” so parents
must keep control of medication.
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Stimulant Medications for ADHD
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How safe are these medications? They have an
excellent safety track record in wide use dating back
before 1968.
How does one start a stimulant medication?
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Typically begin with Concerta, Vyvanse, or Adderall XR
Start with the smallest available size and go up every few days
to obtain a positive effect. If a side effect occurs, stop the
medication. See patient frequently while adjusting medication.
Once the right dose is found, then get the larger pill sizes to
correspond with the right dose.
What if the first medication does not work? Try the other
family. If Concerta doesn’t work, try Adderall XR or Vyvanse.
How do you tell if it is working? Look for a major improvement
in attention and hyperactivity/impulsivity.
What are the side effects to watch out for? Weight loss,
insomnia, irritability, skin picking, and tics, etc. See the PDR.
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Medication Treatment:
Specific Stimulants
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Ritalin Family Mechanism of Action
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Blocks the reuptake of Norepinephrine and
Dopamamine throughout the brain. If it does this in
the appropriate brain circuits, it reduces impulsivity
and activity and enhances attention.
Specific Ritalin Family Medications
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Ritalin Immediate Release Tablets
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Duration: less than 4 hours.
Time to kick in: about 10 minutes.
Doses per day to get 12 hour coverage: 3 to 4.
Reliability: good.
Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved
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Ritalin Specific Medications
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Ritalin SR
– Duration: 6 to 8 hours
– Time to kick in: 20 or 30 minutes
– 1 to 2 Doses per day to get 12 hour
coverage
– Poor Reliability in my experience.
– Strategy to gain longer duration of action:
waxy matrix.
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Ritalin Specific Medications
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Metadate CD
– Duration of action: 6 to 12 hours
– Time to kick in: 15 to 30 minutes
– One to two doses per day to get 12 hour
coverage
– Reliability: good
– Two sets of dissolving beads of Ritalin: one
dissolves immediately, one 4 to 6 hours
later. This achieves bimodal release
Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved
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Ritalin Specific Medications
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Concerta
– Duration of action: 6 to 12 hours
– Time to kick in: 15 to 30 minutes.
– One dose per day to get long duration of
action
– Reliability: very good
– Osmotic chamber to gain longer duration of
action
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Ritalin Specific Medications
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Focalin XR (also available in immediate
release)
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Duration of action: 6 to 12 hours
Time to kick in: 15 to 30 minutes
One or two doses/day to get long duration of action
Reliability: good
Bead system to get longer duration of action
It is the right handed isomer of methylphenidate
(Ritalin is an equal mixture of right and left handed
isomers)
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Ritalin Specific Medications
• Daytrana
– 12 hours or more duration of action
– 30 minutes to kick in
– 1 dose per day to get 12 hour coverage
– Transdermal patch to get longer duration of
action
– Skin irritation can be a problem
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Specific Amphetamine Family
Medications
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Amphetamine Family works by blocking the
reuptake and increasing the release of
Dopamine and Norepinephrine
Specific Amphetamine family medications
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Dexedrine (Dextrostat)
Duration of action: up to 4 hours
Time to kick in: around 15 minutes
3 or 4 doses to get 12 hr coverage
Reliability: good.
No strategy to get longer duration of action
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Specific Amphetamine Family
Medications
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Dexedrine Spansule
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Duration of action: around 6 hours
Time to kick in: around 20 minutes
2 Doses to get long duration of action
Reliability: good
Strategy to get longer duration of action:
primitive form of bead system.
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Specific Amphetamine Family
Medications
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Adderall/ “Mixed Ampehtamine Salts”
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6 to 9 hour duration of action
Time to kick in: around 20 minutes
Doses to get long duration of action: 2 or use
Dextrostat in the afternoon
Good Reliability
Strategy to get longer duration of action: different
half life amphetamines (amphetamine salt,
dextroamphetamine salt, d-amphetamine
saccharate, and d,l-amphetamine aspartate
monohydrate)
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Specific Amphetamine Family
Medications
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Adderall XR (Extended release)
– 6 to 8 hour duration of action
– Time to kick in: around 20 minutes
– Doses to get long duration of action: 1 or 1
plus dextrostat in the afternoon. Sometimes
dosed twice a day.
– Reliability: good
– Strategy to get longer duration of action:
bead system.
Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved
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Specific Amphetamine Family
Medications
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Vyvanse (d-amphetamine liked to lysine)
– The most recent FDA approved stimulant
– Fewer “Drug Like effects” imply less
potential for abuse
– Still Schedule II
– Manufacturer claims of 12 to 13 hour
coverage seem largely valid in my practice.
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Vyvanse (con’t)
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Strategy to get longer duration of action:
– Chemically link amphetamine to lysine
– An enzymatic reaction must cleave the
molecule for it to get into the brain
– There is only “so much” enzyme so the
reaction rate is controlled
– As a result it is hard to get high on this.
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Nonstimulant Medications
for ADHD
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Straterra or “Atamoxetine”
Alpha II Agonists
Wellbutrin or Buproprion
Amantadine or Symmetril
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Straterra or “Atamoxetine”
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It is a “norepinephrine reuptake inhibitor” which
stimulates circuits that use the chemical
norepinephrine as a messenger; some of which
regulate attention and activity.
Safety: looks quite safe, but the FDA required a black
box suicide warning.
The “effect size” appears much smaller than for
stimulants, i.e., while it is better than placebo, it is not
as effective as stimulants. However, a drug company
funded study showed good effect size.
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Straterra or “Atamoxetine” (cont’d)
• It can take a month or more to work and the
dose is based on the weight of the child.
Children over 70 Kg may be worked up to 40 mg
twice a day, occasionally more. The maximal
dose in the PDR is 100 mg a day.
• Side effects include stomach upset, diarrhea,
constipation, tiredness, and mood swings. See
the PDR for a full description.
• It is said to not be an abused medication.
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Straterra or “Atamoxetine” (cont’d)
• I almost always use stimulants first because we
know more about them including in long term
use.
• It is not uncommon to use Straterra as a base
drug and thereby get away with lower doses of
stimulants in order to minimize stimulant side
effects in sensitive individuals and get some
evening reduction in impulsivity.
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Tricyclic Antidepressants
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Members of the class
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Impramine
Desipramine
Clomipramine
Others
Advantages
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Don’t cause sleep disturbance or weight loss.
Work smoothly 24 hours a day.
Effective for severe impulsivity and hyperactivity
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Tricyclic Antidepressants
• Disadvantages
– Deadly in overdose
– Can’t be used if pretreatment QTc is
prolonged
– Can cause dry mouth, sedation, and
constipation
– In laboratory tests of attention, they do not
show efficacy though people say they pay
attention better on them in the classroom
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Alpha II Agonists
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Members of the Class
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Tenex or Guanfacine(New slow release version
marketed as Intuniv).
Clonidine or Catapress
Advantages
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Don’t cause a sleep disturbance
Suppresses tics
Don’t cause weight loss
Often help hyperactive impulsive behavior
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Alpha II Agonists
• Disadvantages
– Don’t improve attention per se.
– Can cause bradycardia and hypotension.
– Have to be dosed tid (Except for Intuniv).
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Wellbutrin or Buproprion
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Advantages
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To the extent that it works, it works 24 hours a day
Does not cause sleep or appetite disturbance
Does not usually exacerbate tics.
Disadvantages
– Seems to have a small effect size
– Has FDA black box suicide warning
– Not really studied for ADHD.
Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved
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Amantadine or Symmetril
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Advantages
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To the extent that it works, it is smooth 24
hour coverage
Does not typically affect, sleep, appetite, or
tics.
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Disadvantages
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No studies on it that are controlled for ADHD.
Very few physicians are familiar with using it for
this purpose.
• The childhood safety studies are only on short
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term use for influenza.
Summary
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Stimulants remain first line do to their large effect
size and long safety record.
The newest timulant, Vyvanse, seems to have the
longest duration of action.
Not all patients tolerate or respond to stimulants.
The only nonstimulants FDA approved for ADHD
are Straterra and Intuniv.
There are other nonstimulant options that
sometimes work well.
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