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Delayed-release stimulant used to treat
ADHD may be less subject to abuse
BOSTON - March 1, 2006 - A team led by Massachusetts General
Hospital (MGH) researchers has found that a delayed-release stimulant
used to treat attention-deficit hyperactivity disorder (ADHD) may
be less likely to be abused than other stimulant drugs. Study participants
taking therapeutic oral doses of Concerta, a once-daily form of
the drug methylphenidate, did not report perceiving and enjoying
the drug's subjective effects, features that are associated with
a medication's potential for abuse. The report appears in the March
2006 issue of the American Journal of Psychiatry.
"We know that drugs that cause euphoria are potentially abusable,
and euphoria requires rapid delivery to the brain. Using sophisticated
PET scan imaging, we were able to examine the rate of delivery of
both rapid- and delayed-release formulations of methylphenidate
and correlate those results with how the drugs felt to study volunteers,"
says Thomas Spencer, MD, of the MGH Pediatric Psychopharmacology
Unit, the paper's lead author. "The ability to show that rate
of brain delivery may determine abuse potential is important to
our understanding of the safety of different formulations."
Methylphenidate and other stimulant drugs used to treat ADHD act
by blocking the dopamine transporter, a molecule on brain cells
that takes up the neurotransmitter dopamine, raising its level in
the brain. Studies have shown that the brains of ADHD patients have
abnormal regulation of dopamine, which plays a key role in the control
of movement, behavior and attention. While stimulants are effective
for controlling ADHD symptoms, the drugs are also subject to abuse,
so the current study was designed to compare the abuse potential
of two formulations of methylphenidate.
The researchers compared a traditional, quick-release form of the
drug with Concerta, a formulation that is released over 12 hours
to produce a gradual increase in blood levels. With Concerta, the
drug passes slowly through a hole in capsules that do not dissolve,
reducing the possibility that the gradual-release feature might
be bypassed. Study participants received the two medications at
dosages designed to produce comparable peak levels in the blood
and brain.
Twelve adult volunteers, none diagnosed with ADHD or any neurological
or psychiatric disorder, were randomly assigned to receive either
the immediate-release or delayed-release form of methylphenidate
on two separate days. PET scans - which showed whether or not the
dopamine transporter molecule was occupied by the medication - were
taken the day before drug administration as a baseline, one and
three hours after the first drug administration and five and seven
hours after a second drug administration on a different day. During
the 10 hours after each drug administration, hourly blood samples
were taken from the volunteers, who also completed hourly questionnaires
regarding whether they were aware of the drug's effects and whether
they enjoyed or disliked those effects.
As expected, the delayed-release formulation took longer to produce
maximum blood levels and blockade of the dopamine transporter than
did the immediate-release drug. While most of those receiving immediate-release
methylphenidate reported detecting and enjoying the drug's activity,
few of those receiving the delayed-release form were aware of or
enjoyed the drug's effects.
"The differing reports on feeling and liking the drug effects
occurred despite using larger doses of the delayed-release formulation
and the equivalent peak blood and brain levels," says Spencer.
"Previous studies have showed that both versions are effective
for treating ADHD. Whether delayed- or sustained-release formulations
of other potentially abusable ADHD drugs share the same safety characteristics
needs be studied, since different forms vary in the levels and timing
of drug delivery." Spencer is an associate professor of Psychiatry
at Harvard Medical School.
The study was supported by grants from the National Institute of
Mental Health and McNeil Consumer & Specialty Pharmaceuticals,
which manufactures Concerta. The study's co-authors are Joseph Biederman,
MD, Bertha Madras, PhD, and Darin Dougherty, MD, of MGH Psychiatry;
Ali Bonab, PhD, Elijahu Livni, PhD, and Alan Fischman, MD, PhD,
of MGH Radiology; and Patrick Ciccone, MD, and Dolly Parasrampuria,
PhD, of McNeil.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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