ADHD-PI and Response to Stimulant Medication

Some people with Inattentive ADHD (ADHD-PI) and some people with Inattentive ADHD and Sluggish Cognitive Tempo respond well to the stimulants and some do not. Genetic studies are helping us understand why this is so. There seems to be an allele of the gene known as ADRA2A, the G allele, that when present makes ADHD Inattentive people MORE likely to respond to the stimulants. That is the stimulants improve their inattentiveness. If this allele is absent then the person will NOT respond to the stimulants.

The researchers involved in the Human Genome Project have said that their work will ultimately lead us to a system of medical treatment that is highly personalized and based on each individual’s genetic make-up. There are many gaps in our understanding of the causes and treatment of ADHD-PI and Sluggish Cognitive Tempo. It is likely though that genetic research will further our understanding of the processes at work in individuals who are inattentive, sluggish or both.

The ADRA2A gene is one of several genes thought to play a role in ADHD-PI. The interesting thing about this ADRA2A gene is that is also involved in hormonal secretion and is known to play a role in Thyroid dysfunction and Diabetes. People with a certain ADRA2A variant are more likely to get Diabetes type II. There is also an ADRA2A relation to thyroid disease, cortisol level, and fatigue.

I have said before that when we know more about inattentive ADHD and Sluggish Cognitive Tempo (SCT) we will see that there is a strong hormonal component to these problems. Genetic studies are moving us closer to a better understanding of the Inattention and sometimes sluggishness associated with ADHD-PI and I believe soon there will be medication specifically targeting the genes that are causing symptoms of SCT and ADHD-PI.

We do not know how this allele affects our response to the non-stimulant medication for ADHD because no one has looked at this allele or gene and the response to Strattera or Clonidine. The stimulants and Strattera both act on the Dopamine and Norepinephrine systems in the prefrontal cortex of the brain. These neurotransmitters play a significant role in hyperactivity and sluggishness. Drugs that enhance alpha(2)-receptor stimulation such as the stimulants and Strattera will improve prefrontal cortex functioning. Clonidine (Guanfacine) directly stimulates postsynaptic alpha(2A)-receptors in the prefrontal cortex and improves functioning. Strattera works more like the stimulants, increasing neurotransmitter stimulation whereas Clonidine works more on the neurotransmitter receptors.

It is likely that the way these drugs act on the prefrontal cortex is related to each individual’s genetic code and because of this, what works for one person with ADHD-PI or SCT will not always work for another person with that same diagnosis.  Since we know that genes play a role in how well these medications will work for each individual with ADHD, it seems that a better understanding of the complex array of gene variations in each people with ADHD would be helpful. I am sure that this type of gene evaluation is in our future.

Though this genetic evaluation may seem kind of ‘creepy’ to some folks, I see the future of genetic evaluation as a good thing for those of us with Inattentive ADHD. It seems to me that until we figure out what genetic puzzle pieces fit into the functional 'hole' causing the problems in Inattentive ADHD and Sluggish Cognitive Temp, we will not be able to adequately treat these problems.


  1. I have the combined type ADHD. Aside from coffee which I consume at intervals during the day, I also take 500mg capsules of L-Tryptophan every 5 hours. It seems to even things out on the stressors side. Like keeping on task and following through - every day...Supposed to help, as amino acid in producing serotonin..Anyone have experience with L-Tryptophan also? ..Seems this combo does help me along with being aware of behaviors....Helps me not be or get so anxious..Nothing will be quite perfect every day...Things change like the weather and the clouds. So if most of the day is good and I get a proper nights sleep (very important), I consider that a good & positive day/night.

  2. The amino acids are supplements that have helped some folks with ADHD. Apparently you have to have just the right amount and combinations of vitamins on board to maximize the benefits.

    I will try to find the link that I read about someone who had looked thoroughly into how exactly the amino acids work.

    Thanks for your comment!!

  3. I would like to know more about alternatives to ritalin. My daughter was just diagnosed with inattentive add. She is 16 & I'm scared of ritalin type drugs. I would like to go natural with her of drugs that are not as bad of side affects as ritalin because she is so young I don't want any long term damage or dangerous side effects for her. Do you have any suggestions where I could start?


  4. Britt,

    I went ahead and wrote a post to answer your question. It can be found at:

    Let me know if I can answer any other questions and thanks for your question, it make me realize that I needed to write a post to make this information more readily available.


  5. I have inattentive type ADD. I understand that with stimulant medications, like almost any other medication, people react in many different ways depending on their brain chemistry/genes. What I don't understand is why I used to be easily "upped" or "racey" by stimulant medications before age 17, then after stopping for 4 years and just recently starting back up, stimulants no longer have a noticeable effect on me. Even at a high dose, they almost seem to make me tired. I just don't understand how it changed. Did my brain chemistry just change? Does this happen throughout life? What causes it, and how big of a role do hormones play in these changes?


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