As you know, DearReader, I enjoy talking about science with the Boss, aka the US taxpayer, aka my friends, neighbors and acquaintances. In fact I not only enjoy it but I think of it as responsibility both to them, the people who fund the NIH, and to my fellow scientists.
You are also likely aware that I have school-aged children and therefore this circle of interactions with the taxpayer includes chatting with the parents of children that my own kids interact with.
One of the conversations that arises fairly frequently has to do with medications prescribed for Attention Deficit Disorder / Attention Deficit Hyperactivity Disorder (ADD, ADHD). This is, of course, a big can of worms to be opening on the blogosphere and let me make it clear I'm not planning on discussing ADHD science per se.
In brief outline of the issues let us reflect on the following.
-as with most of the mental/behavioral disorders there exists a distribution or spectrum of traits, symptoms or behaviors. Depending on how you want to view them. At some point of extremity, we (meaning the clinical psychiatry/psychology communities) define or diagnose conditions as pathological and in need of intervention
-diagnosis is imperfect, we do not have alternate biomarker validation in most cases and there will always be those on the threshold
-specific traits or behaviors can be either trivial or maladaptive depending on circumstances.
-therapeutic intervention, even in the clearly pathological cases, is less than 100% successful.
-interventions which involve repeated or chronic administration of drugs which affect brain and other body systems have risks.
These end up being complicated situations for parents to navigate. Parents are subject to the usual stigmas about mental health, and are reluctant to consider that their child might actually benefit from therapeutic drugs. They are worried about the lasting consequences. They have, perhaps, run across the criticisms (some valid, many not) of ADHD diagnosis and medication that are available on the internet.
And their doctors are failing them.
Weirdest to me, of course, is that doctors do not manage to communicate* the nature of the drugs and what is known about the risks that are of most concern to parents.
We're generally talking about stimulant class medications that are indirect dopamine agonists. This means that they have the effect of increasing the magnitude or duration of action of dopamine in synapses which use this neurotransmitter. (A direct agonist, in contrast, would be a drug which was able to mimic the interaction of dopamine with its target receptor molecules.) The stimulant drugs do this by either blocking the function of the dopamine re-uptake mechanism, enhancing the release of dopamine or both. The prototypical members of the stimulant class that are familiar from the recreational abuse side include cocaine, amphetamine and methamphetamine.
The more familiar ADHD compound methylphenidate is also dopamine transport inhibitor and it appears in a wide range of product names (Ritalin®, Concerta®, Focalin® are just the start). But what do you know? Good old amphetamine (Adderall®, Dexedrine®) and even methamphetamine (Desoxyn®) are medications which are approved to treat ADHD.
In very large part I find that parents are at best aware of the trade names, but have little concept of what is in each product. I should point out as well that the trade names confer subtle differences. Sometimes it is a mere formulation trick of the pills designed to generate a broader duration of target blood levels (e.g., XR standing for 'extended release') rather than the peaky on-off pharmacokinetics of more simple preparations.
Sometimes there are tricks with drug identity. It could be that the salt the freebase drug is bound with differs. Think of powder cocaine which is cocaine bound to the hydrochloride (HCl) salt. The ADHD medication Adderall®, for example, contains a mixture of amphetamine salts including the sulfate, saccharate and aspartate. The body dissociates the freebase molecule with some time involved and the argument is that this is another strategy to control the level of active drug levels at the synapse site in the brain.
Stimulant class drugs also occur as stereoisomers or enantiomers- right and left hand mirror images of the drug molecule. These mirror images can have different pharmacological properties and so sometimes brand names containing the same compound may differ in terms of right (dextrorotary; e.g., dextroamphetamine, d-amphetamine) or left-hand forms of the molecule. Sometimes I speculate that much of this is just patent and new-product IP issues of a for-profit pharmaceutical industry but this is unduly cynical of me. We think of d-amphetamine as being the active isomer and the l-amphetamine being inactive but this is just a relative ratio. The supposedly inactive isomer does have some pharmacological activity. This gives a basis for clinical variability.
You hear reports of varying success/intolerance for specific products with specific kids. I recall one taxpayer/Boss referring to one product as nearly miraculous and a second as "evil" for his/her kid when (IIRC) the root compound was the same. It is likely that individual differences interact with these varying pharmacological properties of individual pharmaceutical products to vary the outcome tremendously.
I don't know where the problem lies but certainly the doctor-parent-kid interaction is not getting the information-transfer job done. Parents remain confused even after many months of the process from when the teachers first mention they might want to get checked for ADHD until meds are prescribed and deployed. Docs can do better and we scientists that know at least a little something about the matter can do better. It would save a lot of parental anguish.
Once parents grasp that ADHD meds are stimulants, they tend to focus on two concerns. Will they stunt my kid's growth? These drugs are appetite suppressants after all and the target population is in critical growth years. A review from 2008 is a decent starting point. It tends to conclude yes, there will be effects on growth and body composition, it doesn't vary much by major drug compound, there seems to be some catch up once meds are discontinued and....it is a really complex situation to try to predict outcome for a specific kid.
Parents also want to know if the drugs will make their kid a drug addict. Very complicated question. Not least of which is a co-morbidity between untreated ADHD and substance use disorders. Pre-existing liability? Self-medication? Environmental factors differentiating the diagnosed and the undiagnosed? ...Like I said, complicated.
Nevertheless there is a recent vignette fielded by the PI of my most important low-N developmental biology project. It had to do with a parent of a highschool aged teen who had recently been put on one of the stimulant class ADHD medications. The doctor had failed to communicate* to this parent that these drugs were being recreationally abused and that there was a significant risk of his kid selling off some of his meds to his buddies. The parent was not aware that it would be a good idea to keep an eye on the meds. This seems to me to be a hugely significant breakdown in the communication between the prescribing doctor and the parents.
We need to do better.
*I use the term "communicate" because I have no idea what the doctors actually say to the parents in question.
Note added in proof: this had nothing to do with this post 🙂
Updated 5/26/10: I've edited the original post a bit to clarify and expand on a couple of points.