Pharmacogenetic
testing for ADHD is testing a patient who has ADHD for certain variant genes
which scientists think may affect their response to certain medications. The idea is that patient genetics could guide
the selection of medication better than the trial and error approach.
Currently
patients can access the following tests on demand at a prescribing pharmacy as
part of a battery of tests: CYPD6,
CY2B6, ADRA2A, and COMT.
CYP2D6 changes atomoxetine into an inactive state. People who are fast metabolizers will need
more medication for the drug to be effective.
However, having this genetic information does not change the practice of
slowly increasing the dose of the medication until it works. People who are slow metabolizers (about 5% of
whites), on the other hand, are more likely to have side
effects, and the manufacturer recommends a lower starting dose for these
patients.
CYP2B6 is thought to be
responsible for the formation of the most potent active metabolite of bupropion
(Wellbutrin). However, the evidence suggests there
probably are more ways that bupropion is metabolized outside of CYP2B6. No study has directly tested the effect of
CYP2B6 variations on the response of ADHD to bupropion, so we don't really know
if bupropion would be ineffective, more effective, or have more or fewer side
effects based on genetic information alone.
ADRA2A codes for receptors
for several different drugs, especially for guanfacine and clonidine, but also
for stimulants like methylphenidate.
Studies conflict as to whether the presence of genetic variations of
this gene predict response to methylphenidate
. Even in the most positive
studies, the correlation is not 100%, meaning that the gene might predict no
response, but there were still patients who responded to the medication. No studies have been done to test whether
variations in ADRA2A are associated with
response of ADHD to guanfacine or clonidine.
COMT codes for an enzyme that breaks down
norepinephrine (a stimulant neurotransmitter) and dopamine (another
neurotransmitter with mixed properties).
Studies conflict
as to whether genetic status allows us to predict whether a patient will
respond to methylphenidate. No studies
have been done on the relation of COMT to response to other ADHD medications.
What is needed is
more studies which use outcomes important to patients to link their genetic
information with which drug will or will not be successful. At present, pharmacogenetic testing mostly
yields information that isn't specific enough to guide decision making or to
change trial and error selection of medication.
References:
"ADHD Medication Testing." Harmonyx. YX
Genomics, 2015. Web. 02 Oct. 2015.
DaSilva, T. L. , T. G. Pianca, T. Roman, M. H. Hutz, S. V.
Faraone, M. Schmitz, and L. A. Rohde. "Adrenergic α2A Receptor Gene and
Response to Methylphenidate in Attention-deficit/hyperactivity
Disorder-predominantly Inattentive Type." Journal of Neural
Transmission J Neural Transm 115.2 (2008): 341-45. Web.
"Find the Right Medication for ADHD with
GeneSight." Find the Right Medication for ADHD with GeneSight.
AssureRxHealth, Inc., 2015. Web. 02 Oct. 2015.
Froehlich, Tanya E., Jeffery N. Epstein, Todd G. Nick, Maria
S. Melguizo Castro, Mark A. Stein, William B. Brinkman, Amanda J. Graham,
Joshua M. Langberg, and Robert S. Kahn. "Pharmacogenetic Predictors of
Methylphenidate Dose-Response in Attention-Deficit/Hyperactivity
Disorder." Journal of the American Academy of Child & Adolescent
Psychiatry 50.11 (2011): n. pag. Web.
Kieling, Christian, Julia P. Genro, Mara H. Hutz, and Luis
A. Rhode. "A Current Update on ADHD Pharmacogenomics." Pharmacogenomics
11.3 (2010): 407-19. Medscape Family Medicine. Medscape. Web. 02 Oct. 2015.
Park, S., J.-W. Kim, B.-N. Kim, S.-B. Hong, M.-S. Shin,
H.-J. Yoo, and S.-C. Cho. "No Significant Association between the
Alpha-2A-Adrenergic Receptor Gene and Treatment Response in Combined or
Inattentive Subtypes of Attention-Deficit Hyperactivity Disorder."Pharmacopsychiatry 46.05 (2013):
169-74. Web.
Polanczyk, Guilherme, Cristian Zeni, Julia P. Genro, Ana P.
Guimarães, Tatiana Roman, Mara H. Hutz, and Luis A. Rohde. "Association of
the Adrenergic α2A Receptor Gene With Methylphenidate Improvement of
Inattentive Symptoms in Children and Adolescents With
Attention-Deficit/Hyperactivity Disorder." Arch Gen Psychiatry Archives
of General Psychiatry 64.2 (2007): 218. Web.
Strattera
[package insert]. Lilly USA , LLC., Indianapolis , IN
Wellbutrin
[package insert]. GlaxoSmithKline, Research Triangle Park , NC
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