PET-designed ADHD treatment lowers risk of abuse

Imaging of the brain with a carbon-11 radioligand showed that a slow-release formula of a stimulant drug used to treat attention deficit/hyperactivity disorder is as effective as the rapid-release version. The controlled-release preparation is less likely to be abused.

Methylphenidate acts by blocking the dopamine transporter, which augments dopamine activity in the frontal cortex and improves a child's ability to pay attention. Rapid increase of dopamine activity in other brain areas is perceived as pleasurable and can lead to patient abuse of the drug.

Dr. Thomas J. Spencer, assistant director of the pediatric psychopharmacology unit at Massachusetts General Hospital, and colleagues used PET imaging and C-11 altropane to investigate a new once-a-day capsule developed to release methylphenidate more slowly. Instead of dissolving in the gastrointestinal tract, it absorbs body fluids and uses osmotic pressure to gradually push the medication out of the capsule.

The researchers evaluated 12 healthy adults who were randomly assigned to receive immediate-release or osmotic-release methylphenidate. They reported their results in the March 2006 issue of the American Journal of Psychiatry.

PET imaging showed that the 90-mg capsule with sustained osmotic release produced the same blockade in the brains of healthy adults as 40 mg of immediate-release methylphenidate. These effects occurred more slowly, however, with the osmotic-release capsule.

"The study represents the first use of PET imaging to detect directly what is happening in the brain during the treatment of ADHD and to use that information to improve treatment," said AJP editor-in-chief Dr. Robert Freedman.

Study participants were asked about their subjective reactions to the two different capsules. Subjects taking the 40 mg of immediate-release methylphenidate reported a mild effect. Those taking the 90 mg controlled-release formula reported significantly less detection of an effect, suggesting less likelihood of future abuse.

"These findings corroborate that the relevant variable for the reinforcing effects of stimulant drugs is the rate at which dopamine increases (change in dopamine concentration per time unit) rather than dopamine level per se," wrote Dr. Nora D. Volkow, director of the National Institute on Drug Abuse, in an accompanying editorial.

The study provides an example of how imaging technologies can be used to predict the likelihood that a drug will have reinforcing effects by directly monitoring the temporal course of their effects in dopamine targets in the human brain, she said.

For more information from the Diagnostic Imaging archives:

Pot smokers, schizophrenics show similar brain responses

Diffusion tensor imaging reveals cause of ADHD

F-18 DOPA imaging guides stem cell treatment of Parkinson's disease

Imaging shows effects of alcohol use on brain