medication treatment of adhd csno conference february 9, 2013 thomas s. jensen, md 10505 sorrento...

MEDICATION TREATMENT OF ADHD

CSNO Conference February 9, 2013

Thomas S. Jensen, MD10505 Sorrento Valley Road, Suite 390

San Diego, CA 92121619/225-2220

[email protected]

Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved 2

Stimulant Medications for ADHD

• 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.

– The Ritalin Family (Ritalin, Focalyn, Focalin XR Ritalin SR, Concerta, Metadate, Daytrana Patch)

– The Amphetamine Family (Adderall, Adderall XR, Dexedrine, Dexedrine Spansule, Vyvanse).



• 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:

– 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



• 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.



• 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?– 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.


Medication Treatment:Specific Stimulants

• Ritalin Family Mechanism of Action– 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– Ritalin Immediate Release Tablets

• 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.


Ritalin Specific Medications

• 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.



• 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



• 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



• Focalin XR (also available in immediate release)

– 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)



• 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


Specific Amphetamine Family Medications

• Amphetamine Family works by blocking the reuptake and increasing the release of Dopamine and Norepinephrine

• Specific Amphetamine family medications– 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



• Dexedrine Spansule– 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.



• Adderall/ “Mixed Ampehtamine Salts”– 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)



• 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.



• 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.


Vyvanse (con’t)

• 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.


Nonstimulant Medications for ADHD

• Straterra or “Atamoxetine”

• Alpha II Agonists

• Wellbutrin or Buproprion

• Amantadine or Symmetril


Straterra or “Atamoxetine”

• 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.


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.


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.


Tricyclic Antidepressants

• Members of the class– Impramine– Desipramine– Clomipramine– Others

• Advantages– Don’t cause sleep disturbance or weight loss.– Work smoothly 24 hours a day.– Effective for severe impulsivity and hyperactivity


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


Alpha II Agonists

• Members of the Class– Tenex or Guanfacine(New slow release version

marketed as Intuniv).– Clonidine or Catapress

• Advantages– Don’t cause a sleep disturbance– Suppresses tics– Don’t cause weight loss– Often help hyperactive impulsive behavior


Alpha II Agonists

• Disadvantages– Don’t improve attention per se.– Can cause bradycardia and hypotension.– Have to be dosed tid (Except for Intuniv).


Wellbutrin or Buproprion

• Advantages– 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.


Amantadine or Symmetril

• Advantages– To the extent that it works, it is smooth 24 hour

coverage– Does not typically affect, sleep, appetite, or tics.

• Disadvantages• 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 term use for influenza.


Summary

• 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.

medication treatment of adhd csno conference february 9, 2013 thomas s. jensen, md 10505 sorrento...

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