AttentionDeficit Hyperactivity Disorder

A Psychopharmacology Primer Patrick Shea MD R4 Triple board

What does ADHD look like?

Jimmy, an 8-year-old boy is undergoing a psychoeducational evaluation. He is very distracted in his classroom and has trouble staying in his seat. His teachers describe him as well-adjusted, with good self-esteem. He is a good athlete, eats a nutritious diet, and has no problems with sleep. His full-scale IQ is 87, but there is inconsistency in responses; Jimmy scored much better on the items that were administered earlier in the session. Parents report that at home, Jimmy is a good boy but very distractible and has to be kept on task to get through simple chores or even a meal as a family.

Cues to the diagnosis

Distracted, trouble staying in his seat, BUT well adjusted with good self-esteem No mention of oppositional behavior or aggression Home life described as stable IQ testing inconsistency is not subject-specific but pattern of doing better on earlier questions No overall global delay or across-the-board low IQ score No mention of mood or anxiety symptoms

Jimmy, continued
Parents and teachers administer a Vanderbilt, which shows probable AD/HD diagnosis. Parents would like to start medication therapy in hopes of improving Jimmys school performance. You elect to start a stimulant medication.

Why is this topic confusing?

Heres a list of medications used to treat AD/HD by generic name, courtesy of Stahls Prescribers Guide: Armodafinil Amphetamine (d) Amphetamine (d,l) Atomoxetine Bupropion Chlorpromazine Clonidine Guanfacine Haloperidol Lisdexamfetamine Methylphenidate (d) Methylphenidate (d,l) Modafinil Reboxitine

Stimulants: Basic principles

They work by blocking reuptake of norepinephrine and dopamine (amphetamine also facilitates release of these neurotransmitters). 2 basic flavors: Methylphenidate and Amphetamine Some children respond better to one or the other (individual variation). Family hx can help guide you where applicable. All stimulants are schedule 2, with the attendant hassles: Need signed paper Rx and individual 30day prescriptions. Side effects to monitor: Sleep, appetite, growth, and blood pressure.

Stimulant dosing

Regular formulations: dose twice a day, once in the AM and once ~6 hours later (usually given at school around lunch time) This is a hassle but often substantially less costly Do NOT give the 2nd dose after 2 PM (sleep disturbance) Once daily (QAM) is much easier, but none of these are generic yet.

D,L-Methylphenidate
AKA

original methylphendate, Ritalin Starting dose is 5 mg + 5 mg. Go up by 510 mg/week and titrate to effect to max of 40-60 mg/day. Dose duration 3-4 hours. FDA approved for kids 6+ with ADHD Cheapest regimen by far: $18-25 per month. Older with tried and true data for efficacy.

Methylphenidate: longer acting forms

Older

ER/SR. Duration of action: ~6 hours Some children may be able to get by with one dose. Otherwise, same dosing schedule as immediate release. A bit more costly, but generic ($3040/month).

long-acting forms: Methylphenidate

Newer methylphenidate formulations

Concerta is a newer extended release form of methylphenidate with QAM dosing. Dosing is 18 mg QAM to start then up by 9 mg weekly titrating to effect. Its NOT generic, so $220/month. Focalin is d-methylphenidate (dexmethylphenidate), so twice as potent. It can sometimes work for non-responders to regular methylphenidate. Dosing is 2.5 twice a day and up in increments of 2.5 titrating to effect. Duration is about 4 hours, and its about $100/month. Focalin XR is QAM dosing but again, expensive at $215 per month.

D,L-Amphetamine

Usually goes by the name Mixed amphetamine salts on the boards. You know it as Adderall. FDA approved for children ages 3(!)-12 XR formulation approved for 12-17 Same basic dosing as methylphenidate: Start with 5 and 5, titrate to effect. XR is QAM dosing. Max dose is 30-40 mg/day Sometimes works in patients with inadequate response to methylphenidate Higher street value (and abuse potential?) than methylphenidate Cost: Generic regular form is $80-100/month (?) and Adderall XR is $250-300/month.

D-Amphetamine

Also known as dextroamphetamine, Dexedrine. 3-4 hour duration of action. Same dosing: 5+5, max 40, titrate to effect weekly (see, this is easier than you thought, right?) Cost=$25-$40/month generic Sustained-release has 8 hour duration and is generic, $90-200/month. Duration is about 8 hours, many children can get by on one dose, but others need an extra immediate-release dose in the afternoon.

Lisdexamfetamine

Also known as Vyvanse. And no, I dont know why the generic name has an F instead of a ph. Prodrug of dextroamphetamine Long duration 10-12 hrs with QAM dosing. Start 10 mg go up by 10/week to max of 70. Low abuse potential as it is a prodrug of a sustained-release formulation. Cost: Around $200 per month.

Back to our case

You offer Jimmys parents a few different options and after weighing the risks and benefits, you and parents decide on long acting form of dextroamphetamine. Jimmys attention and concentration improve significantly, and he is doing better in school, but parents notice his appetite falling off. After watching for a few months to see if he will outgrow this effect, a significant slow-down in weight gain is noted. Although you feel comfortable watching for a bit longer (his linear growth hasnt changed), parents are really worried about this and would like to get him off of the stimulant, but still treat his AD/HD to sustain improvement in school peformance.

So, now what do you do?

Luckily there are other options. SNRI (Atomoxetine) Alpha-2 agonists (clonidine, guanfacine) Behavioral therapy. In fact, medication + therapy combination is the MOST effective for ADHD. Others medications are out there but arent FDA approved for AD/HD, kids, or both, and therefore arent used very often.

Atomoxetine

You know this as Strattera Its an SNRI: Serotonin/Norepinephrine Reuptake Inhibitor. Thus, it works similarly to the SNRI antidepressants, like venlafaxine. This is good to know because its similar to antidepressants in that it will usually take longer to take effect than the stimulants, so must be sure trial is adequate. Advantage: Can use where stimulants are contraindicated (growth problems, HTN, cardiac history, others..) Also doesnt tend to cause the problems with appetite suppression and sleep disturbance that the stimulants can. No known abuse potential Dosing: 0.5 mg/kg to start, then can go up to 1.2 mg/kg. Max is 80100 mg/day. Its QAM dosing. Not generic. Cost is $220-280 per month.

Alpha-2-adrenergic agonists
These

work by binding said alpha-2 adrenergic receptors. This results in presynaptic inhibition of further sympathetic output and causes an overall anti-adrenergic response producing sedation, vasodilation, etc. These medications are also sometimes used as hypertensives (Catapres) and for sleep.

Clonidine

Binds to all 3 major alpha-2 receptor subtypes, creatively named A, B, and C. Also binds the Imidazoline receptor (A dirty alpha2 agonist) As a result, it causes a good deal of sedation and hypotension along with occasional dry mouth and constipation. Advantage: Kids with more aggression symptoms Dosing: Usually twice daily, and unlike stimulants its dosed at bedtime (sedating). Can also be used p.r.n. for aggression/agitation. Typical range is 0.1-0.4 mg/day. Kapvay is a newer extended-release formulation of clonidine that is FDA approved for children ages 6-17. It costs $170 a month. Regular Clonidine is a very old drug (initially marketed for hypertension) so no incentive to really trial/study it for ADHD, but still used relatively frequently. Its on the $4 list.

Guanfacine

A cleaner alpha-2 agonist that binds only the alpha-2A receptor. Thus, fewer side effects in terms of sedation and hypotension though sedation is still common. Advantageous for aggression or when a stimulant is contraindicated. Similar to the situation with clonidine, Intuniv is a newer long acting form that is FDA approved for children 6-17. Youve probably heard of itTheyre always running that ad with the mom putting her son on the bus. Intuniv will run about $225 per monthregular guanfacine is on the $4 list. Dosing- Usually start with 1 mg qhs, go no higher than 2 mg bid (for regular guanfacine, which you might also know as Tenex).

A few others (just for fun)

Bupropion (AKA Wellbutrin, Zyban) is not FDA approved but frequently used for ADHD offlabel, more for adults than children. Efficacious because its an NDRI so increases the same neurotransmitter activities the stimulants do. Modafinil and its cousin Armodafinil (Provigil and Nuvigil, respectively) are very, very occasionally used for ADHD again more in adults. They act on the tuberomammary nucleus of the hypothalamus to promote wakefulness.

Case conclusion
After a discussion with parents, you elect to start Atomoxetine since they are insured and dont want Jimmy to be sedated. After a week parents call because they are frustrated that things havent turned around sooner. You remind them that Atomoxetine requires a longer trial. 2 months later at his well child visit, Jimmy has improved in school but is still occasionally off-task; despite this, parents would like Jimmy to stay on atomoxetine to avoid any more stimulant side-effects. You refer them to a behavioral therapist and he continues to improve.

Sources
1. 2.

3.

Stahl, Stephen M. The Prescribers Guide: 4th Edition. Cambridge University Press, 2011 Consumer Reports Health Evaluates: Best Buy Drugs for treating Attention-Deficit Hyperactivity Disorder. 2012. Online pdf. http://www.consumerreports.org/health/res ources/pdf/best-buy-drugs/ADHDFinal.pdf Pediatrics Review Education Program SelfAssessment. 2011. American Academy of Pediatrics.

Questions?