The Quarterly Consultis a quarterly supplement to the Bulletin highlighting pediatric clinical expertise. If you have an item of interest to include in the Quarterly Consult, contact Dr. Steve Dassel at 206-625-7373, mailbox 8588.

By Steve Dassel, MD

It's right around the time that parents receive the first progress report for the 2006 to 2007 school year. Parents who are concerned about underachievement often ask about the possibility of ADHD.

I discussed the subject of managing ADHD with Dr. Chris Varley, clinical program director of Inpatient Psychiatry at Seattle Children's Hospital.

He is also professor of child and adolescent psychiatry and director of the child and adolescent psychiatry training program at the University of Washington.

Q: Before we get to management, let's start with diagnosis. The American Academy of Pediatrics suggests pediatricians use the Vanderbilt questionnaire. What do we know about the sensitivity and specificity of this test?

A: The Vanderbilt reflects DSM IV criteria for diagnosis. I don't know about the particulars of its sensitivity and specificity, but I do know that it lacks concordance between reporters.

In a study in Nashville about four years ago, 23% of teachers rated a group of students as positive for ADHD. However, parents rated only 4 to 5% of that same group as positive.

So, it has its limitations, but the advantage is that it also looks at the comorbidities of oppositional defiant behavior, conduct disorder, anxiety and depression, as well as ADHD.

Q: What do we know about the efficacy of the various forms of managing ADHD?

A: The classic study was done in the 1990s by the National Institute of Mental Health. They looked at 650 kids rigorously diagnosed with ADHD. There were four treatment groups in the study.

The first group of patients was sent back to their primary care doctors with a diagnosis of ADHD for treatment as usual. A second group got only medications. Methylphenidate was used initially in this particular study. If the response was not satisfactory, they were switched to an amphetamine.

Because it was an old study, if satisfactory results were not achieved, they tried pemoline next, and finally tricyclic antidepressants.

A third group received intensive behavioral management. The fourth group was given a combination of stimulant medications and intensive behavioral management.

The research showed that inattentive symptoms responded best to options two and four, while anxiety and aggressive symptoms responded best to options three or four. Those who responded well to option four achieved those results with lower doses of stimulant medication.

Q: Give us a little history of stimulant medication used for ADHD.

A: The most studied stimulant medication has been methylphenidate. This was followed closely by amphetamine agents. These drugs must have been used for at least 50 years in the treatment of ADHD.

More recent are the Adderalls, which are 75% dex and 25% levo isomers; followed by dexmethylphenidate or Focalin, and quite recently, Focalin XR, the long-acting form. A newer medication is atomoxetine, brand name Strattera, which has been available for about three years.

A new transdermal patch delivery system of methylphenidate, brand name Daytrana, came out in June 2006.

Q: Which of all of these drugs should we know about and include in our armamentarium?

A: I think you need to be familiar with a broad range of long-acting stimulant medications. You should know about methylphenidate, such as Concerta, Metadate CD, Ritalin LA and Daytrana.

You will find useful the long-acting amphetamine Adderall XR and the dex isomer of methylphenidate, Focalin XR. I don't think there is a need to start with the short-acting forms to find a proper dose of the long-acting form.

Q: Do stimulant medications have any curative potential?

A: The medications don't cure ADHD, in the sense of permanently changing underlying brain pathology.

Some patients on medication will not show any symptoms of ADHD. Generally you should expect improvement rather than normalization.

Q: What percentage of patients diagnosed with ADHD will improve with stimulant medication?

A: You can expect 70% of your patients to improve significantly, whether you start with methylphenidate or with an amphetamine. I think it is acceptable to start with either.

If you don't get satisfactory improvement at satisfactory doses and you switch to the other stimulant medication, half of the 30% who didn't respond initially will improve.

That means you can expect 85% of your patients to show significant improvement if you start with a low dose of a stimulant medication and build up to adequate or maximum dosage, switching to the other stimulant if necessary.

Q: In that remaining 15%, is it useful to try Focalin XR or Strattera?

A: I think it is reasonable to try these other agents, especially if you are pretty sure of your diagnosis. That's why it's prudent to start with Vanderbilt questionnaires or other standardized measures.

Q: Do you consider a reduction of at least 30% of symptoms a good improvement?

A: Yes.

Q: You recommended starting with a low dose and slowly increasing to a maximum dose. What are those maximum doses?

A: For methylphenidate taken orally, such as Ritalin, Concerta and Metadate, but not patch technology, the maximum dose is generally 2 mg/kg and lower for a big adolescent.

I would be uncomfortable going higher than 80 mg total daily dose. A 60 mg total daily dose would be the maximum that I would use for 6 to 12 year olds, and 20 mg total daily dose maximum in children under 6.

The doses with the patch are about one half the oral dose.

Q: What doses of amphetamines would you recommend?

A: Amphetamines are about twice as potent as methylphenidate, so I would usually go no higher than 1 mg/kg.

I recommend 50 mg total daily dose in the adolescent, 20 to 40 mg total daily dose maximum for the 6 to 12 year old and 10 mg total daily dose maximum for children under 6.

Q: What about Focalin?

A: Well, in theory you give half the dose of the dexmethylphenidate that you would use for the methylphenidate.

However, that often leads to off-label diagnoses because the FDA states there is no additional benefit at any age for a total daily dose of Focalin greater than 20 mg. I would stay at 30 mg or less in the 6 to 12 year old.

For a big adolescent, I would recommend a maximum of 40 mg per day, and for a patient under 6, a maximum of 10 mg per day.

Q: What about atomoxetine?

A: The maximum dose is usually not more than 1.4 mg/kg/day.

Q: So you are comfortable treating children under 6 with stimulant medication?

A: I recommend implementing a behavior management intervention in children under 6 before using medications. They are more difficult to diagnose and have more problems with side effects.

Q: Is there a place for an immediate release stimulant medication?

A: The medication is the same in the immediate and extended release agents. Extended products have the advantage that they often need to be given only once a day.

Immediate release stimulants are much less expensive. They may be an option if multiple administrations of a medication are not a problem.

Even though the extended release preparations do last longer, some children will need to take an immediate release preparation later in the day to maintain treatment effect into the evening.

Q: Let's discuss the issue of side effects of stimulant medication, starting with the cardiovascular concern.

A: The recent deliberations leading to an FDA warning on stimulant medication labeling have been interesting. There are scant data to support the need for a warning and the vote of the expert panel was very close - eight in favor of adding a warning and seven opposed.

Practitioners need to discuss the matter with patients and their parents, and follow and document vital signs - blood pressure, heart rate and cardiac rhythm.

There is no evidence of untoward cardiovascular events associated with stimulant medications, but they are sympathomimetics and can increase heart rate and blood pressure.

Q: What about sleeplessness and decreased appetite?

A: These are usually not long term problems and may subside over time. Sleep issues may respond to adjusting the time of administration.

The onset of the effect is often less than 30 minutes, so it can be helpful for a patient with decreased appetite to take the medication after breakfast, and also to eat when the medication is at its lowest level.

A late evening meal or snack may be helpful. Occasionally it may be necessary to switch medications.

Q: What about using sedatives and appetite stimulants?

A: I have no experience with appetite stimulants. As to sleep problems, I have occasionally used clonidine hs to assist a child in getting to sleep.

Benadryl and melatonin have been used by others.

Q: Discuss the use of Strattera for us.

A: Brand name Strattera, generic name atomoxetine - it is less effective. It has the benefit of convenience, in that you are able to call in a prescription.

Its side effects are different from those associated with stimulants; most commonly it can cause nausea and lethargy. There have been very rare reports of liver toxicity.

It is probably not useful to do routine liver function tests, but atomoxetine should be stopped if any signs of liver toxicity emerge. Also, there is no abuse potential with atomoxetine and it can be helpful with the comorbidities of anxiety or depression.

Q: How do you handle that frequent comorbidity of anxiety/depression?

A: First consider that some "depression" may actually be despondency over failure to achieve. In that case, the patient would respond to an ADHD stimulant medication.

When confronted by both ADHD and anxiety/depression, I treat the ADHD first and evaluate response. Anxious and depressed kids with ADHD do respond to stimulant medication, but not as robustly as kids without that comorbidity. You can also consider atomoxetine as therapy for the ADHD.

If the patient's ADHD symptoms respond to stimulants, but depression persists, you can add an SSRI such as Prozac. You can use a combination of stimulant medication and atomoxetine in the anxious depressed kid with ADHD.

Q: Finally, what mistakes are made by primary care doctors in treating kids with ADHD?

A: The most common mistake is trying one drug and one dose, and giving up if you don't get a good response. I need to emphasize that you start on a low dose and titrate up as necessary to get the best effect.

If a good effect is not obtained, then you need to switch to another medication. If you are going to treat ADHD, and primary physicians certainly are able to, then you have to do it right.

You have to know a broad armamentarium of medications and follow and look for comorbidities, drug abuse and side effects.

Thanks for the review, Chris.