An article by Thomas J. Spencer, M.D, on a new study in the March 2006 issue of The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association (APA), shows how brain imaging is used to identify a form of methylphenidate, a stimulant drug used to treat patients with attention deficit/hyperactivity disorder (ADHD), that is less likely to be abused during treatment.

The study, "PET Study Examining Pharmacokinetics, Detection and Likeability, and Dopamine Transporter Receptor Occupancy of Short- and Long-Acting Oral Methylphenidate," conducted by Dr. Spencer, Assistant Director of Massachusetts General Hospital Pediatric Psychopharmacology Unit, investigates 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 slowly push the medication out of the capsule.

Methylphenidate increases attentiveness for patients with ADHD and lowers their hyperactivity. However, methylphenidate, like other stimulants, can also be abused by patients. Methylphenidate acts by blocking a protein called the dopamine transporter, which transports the neurochemical dopamine out of brain synapses. Blockade of the dopamine transporter by methylphenidate augments dopamine activity in the frontal cortex and improves the children'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 methylphenidate.

Twelve healthy adults were randomly assigned to receive single doses of immediate-release methylphenidate or osmotic-release methylphenidate. Using positron emission tomography (PET), Spencer conducted a clinical comparison of conventional tablets and the new osmotic capsules. The new capsules succeeded in producing an adequate effect on neurotransmission, with fewer reports of pleasurable effects associated with abusable behavior.

PET scanning, the most sophisticated brain imaging technique for measuring dopamine transporter blockade, 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, but these effects occurred more slowly 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 Robert Freedman, M.D., AJP editor-in-chief.

Study participants were asked about their subjective reactions to the two different capsules; those taking controlled-release methylphenidate reported significantly less detection of an effect and less liking of the effect. Detecting and liking a drug's effects signal future abuse potential. Therefore, the controlled-release preparation offers the benefit of once-a-day dosing for patients with ADHD with less likelihood of future abuse.

The main features of ADHD include hyperactivity, impulsiveness, and an inability to sustain attention or concentration. These symptoms occur at levels that cause significant distress and impairment and are far more severe than typically found in children of similar ages and developmental levels. ADHD is a neurobiological disorder that can persist from childhood through adolescence and continue into adulthood.

The "PET Study Examining Pharmacokinetics, Detection and Likeability, and Dopamine Transporter Receptor Occupancy of Short- and Long-Acting Oral Methylphenidate," study is supported by the National Institute of Mental Health and McNeil Consumer & Specialty Pharmaceuticals.

(Am J Psychiatry. 2006; 163: 387-395).

About the American Journal of Psychiatry

The American Journal of Psychiatry, the official journal of the American Psychiatric Association, publishes a monthly issue with scientific articles submitted by psychiatrists and other scientists worldwide. The peer review and editing process is conducted independently of any other American Psychiatric Association components. Therefore, statements in this press release or the articles in the Journal are not official policy statements of the American Psychiatric Association. The Journal's editorial policies conform to the Uniform Requirements of the International Committee of Medical Journal Editors, of which it is a member. For further information about the Journal visit ajp.psychiatryonline.

About the American Psychiatric Association

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