One of my favorite things since opening The Deprescribing Clinic has been working with kids with ADHD. I've encountered numerous parents who arrive frustrated and fatigued, seeking help because they've experimented with multiple medications for their children without success. To make matters worse, these attempts have led to undesirable side effects. The children are usually tired of the ineffectiveness of the medications and the negative impact on their well-being, which often discourages them from being open to trying another medication. However, there is hope. The answer might be a simple cheek swab!
Did you know there is a genetic component to whether or not certain ADHD medications will work? One of the most common medications used is brand name Ritalin or the generic name Methylphenidate. Two different genes can help predict whether Methylphenidate will be effective: the ADRA2A gene and COMT activity. Today we will talk about COMT activity. (My next blog post will cover the ADRA2A gene).
COMT is an enzyme that breaks down dopamine and norepinephrine in the brain. These two neurotransmitters help with attention span and impulse control. There are two different variants of the COMT gene: Val and Met. The “Val” variant has higher activity and so individuals with the Val variant have lower dopamine levels in their brain. The “Met” variant has lower COMT activity. Individuals with the Met variant have higher dopamine levels in their brain.
Methylphenidate is a medication that blocks the reuptake of dopamine and norepinephrine in the brain so there is more available. More dopamine and norepinephrine can improve attention span and impulse control.
Methylphenidate is predicted to have a favorable response in individuals with the Val variant. Why? Because individuals with the Val variant have high COMT activity and breakdown dopamine quickly, they naturally have less dopamine in their brain.
Methylphenidate will increase their dopamine levels to aid in concentration and impulse control.
Individuals with the Met variant have lower COMT activity and already have higher dopamine activity in their brain. These individuals are predicted to have less response to methylphenidate.
While the COMT gene is helpful to predict effectiveness of methylphenidate, it is only one piece of the puzzle. I will discuss another piece next week.
As always, consult your healthcare professional prior to making any medication changes.
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Sources:
Cheon, K. A., Jun, J. Y. & Cho, D. Y. Association of the catechol-O-methyltransferase polymorphism with methylphenidate response in a classroom setting in children with attention-deficit hyperactivity disorder. Int Clin Psychopharmacol 23, 291-298, doi:10.1097/YIC.0b013e328306a977 (2008).
Kereszturi, E. et al. Catechol-O-methyltransferase Val158Met polymorphism is associated with methylphenidate response in ADHD children. Am J Med Genet B Neuropsychiatr Genet 147B, 1431-1435, doi:10.1002/ajmg.b.30704 (2008).
Park, S. et al. Catechol-O-methyltransferase Val158-Met polymorphism and a response of hyperactive-impulsive symptoms to methylphenidate: A replication study from South Korea. J Psychopharmacol 28, 671-676, doi:10.1177/0269881114527654 (2014).
“How the COMT Gene Impacts Mental Health Treatment”, Genomind. February 23, 2023. https://genomind.com/providers/comt-gene-spotlight/#:~:text=Val158met%20(rs4680)%20is%20a%20common,leading%20to%20increased%20dopamine%20activity.
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