Response to ADHD Medication May Be in The Genes
22 Aug 2005  

Testable genetic differences might be used to predict the effectiveness of a medication commonly prescribed to treat attention deficit hyperactivity disorder, a new study suggests.

"This is an exciting finding because ADHD is such a common disorder and it's often difficult to know how patients will respond to ADHD medications," said Dr. Mark Stein, principal investigator of the study and director of the Hyperactivity, Attention, and Learning Problems Clinic at the University of Illinois at Chicago. "Our hope is to take a lot of the guesswork out of why some people respond to these medications and others do not."

The study found that children with a variant form of a dopamine transporter gene -- a variant known to be associated with ADHD -- responded poorly to one of the most common stimulant medications, methylphenidate. The transporter gene encodes a protein on the nerve cell membrane that helps to clear the neurotransmitter dopamine from the nerve junction.

Stein, a clinical psychologist and researcher who specializes in ADHD, and Dr. Edwin Cook, UIC professor of psychiatry, first reported an association of this gene with ADHD 10 years ago. In the new study, Stein, Cook and their co-workers examined the relationship between the gene and patients' medication response over a four-week period, first on a placebo and then on three increasing dosages of methylphenidate.

The researchers tested 47 children with ADHD between 5 and 16 years old to determine which variant of the dopamine transporter gene they carried. They focused on two specific variants -- called 9R and 10R -- of the transporter gene and evaluated how varying doses of methylphenidate would affect ADHD symptoms, impairment, and stimulant side effects.

The majority of the patients had one or two copies of the 10R variant. Of these children, nearly 60 percent had excellent response to the highest dosage (54 milligrams). In contrast, of the patients with two copies of the 9R variant, none displayed such dramatic improvement.

Stein says it is not known precisely how the genetic variations prevent patients from responding to stimulant treatment. The next step, he says, will be to determine whether these patients respond to an alternative drug.

He will soon begin recruiting subjects for a larger study to evaluate children with ADHD on two other medications to see if their genes predict who will respond to either or both drugs.

Stein, whose research interests include pharmacogenetics -- the interaction of drugs and genes -- is cautiously optimistic about the prospects.

"Pharmacogenetics has great promise in ADHD, since the effects of medication range from a dramatic positive effect in many individuals while a minority display side effects or do not respond," he said. "Since ADHD often runs in families, it seems likely that genetics may play a large role in predicting medication response. But we're not yet at the point that we can use these findings in clinical practice. The hope is that eventually we can identify someone who is likely to benefit from a specific dose or at risk of having a severe side effect who could be treated more successfully with a different treatment approach."

ADHD is one of the most common neuropsychiatric disorders in children and adolescents. Many different medications are available to treat ADHD, yet little data exists to guide treatment choices, which often must be based on trial and error.

When a patient does not respond to an ADHD medication, Stein says, that patient may resort to alternative therapies that are ineffective or dangerous or abandon treatment entirely.

"There has always been an art to choosing and titrating medications for ADHD," he said. "It would be tremendous if we could scientifically predict medication response or non-response prior to beginning treatment."

Results of the current study appear in the July issue of the journal Neuropsychopharmachology. The research was funded by the National Institute of Mental Health and the General Clinical Research Center Program of the National Center for Research Resources.

Other authors on the paper include Soo-Jeong Kim at UIC, Irwin Waldman at Emory University, and Christopher Sarampote, Karen Seymour, Adelaide Robb and Charles Conlon at Children's National Medical Center.

Stein and his colleagues at the Institute for Juvenile Research at UIC conduct research and provide comprehensive clinical care for children and adults with ADHD. For more information about the University of Illinois Medical Center's Hyperactivity, Attention, and Learning Problems (HALP) Clinic for children, call (847) 412-0098. For information about the Adult ADHD Clinic, call (312) 996-2389.

For more information about UIC, visit http://www.uic.edu

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