1. 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 tsjensenmd@yahoo.com

2. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved2 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).

3. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved3 Stimulant Medications for ADHD 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

4. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved4 Stimulant Medications for ADHD 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.

5. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved5 Stimulant Medications for ADHD 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.

6. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved6 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.

7. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved7 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.

8. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved8 Ritalin Specific Medications 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

9. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved9 Ritalin Specific Medications 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

10. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved10 Ritalin Specific Medications 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)

11. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved11 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

12. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved12 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

13. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved13 Specific Amphetamine Family Medications 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.

14. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved14 Specific Amphetamine Family Medications 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)

15. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved15 Specific Amphetamine Family Medications 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.

16. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved16 Specific Amphetamine Family Medications 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.

17. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved17 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.

18. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved18 Nonstimulant Medications for ADHD Straterra or “Atamoxetine” Alpha II Agonists Wellbutrin or Buproprion Amantadine or Symmetril

19. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved19 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.

20. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved20 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.

21. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved21 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.

22. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved22 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

23. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved23 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

24. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved24 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

25. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved25 Alpha II Agonists Disadvantages –Don’t improve attention per se. –Can cause bradycardia and hypotension. –Have to be dosed tid (Except for Intuniv).

26. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved26 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.

27. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved27 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.

28. Copyright 2008 Thomas S. Jensen M.D. All Rights Reserved28 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.