Monday, August 28, 2000
Attention deficit hyperactivity disorder (ADHD) has become
crowded with companies stepping forward with products to take on Novartis AG's
Ritalin and Ritalin SR (sustained release) methylphenidates. With a fresh FDA
approval in hand, Alza Corp. is set to launch its Concerta extended release
methlyphenidate, adding to the other approved generic methylphenidates and amphetamine-based
treatments. On their heels are five companies that have filed NDAs for ADHD
compounds or have products in Phase II or Phase III trials.
At the same time, recent reports in the August issue of the
Journal of the American Academy of Child and Adolescent Psychiatry, have
suggested that ADHD is over-diagnosed and over-treated in the U.S., while Europeans
scoff that ADHD is an imaginary disease known only in America.
The debate over the rate of ADHD diagnosed in the U.S., and
the absence of treatment in Europe, thus may provide mixed messages about the
market opportunity. But physicians and psychiatrists who spoke to BioCentury
generally believe that ADHD has been under-prescribed and blame misdiagnosis
for inappropriate treatments with drugs for ADHD.
The clinical definition of ADHD is a neurobiological disorder
with primary symptoms of hyperactivity, impulsivity, and the inability to maintain
concentration. Patients must experience two or more of these symptoms in multiple
settings, for example at home and at school. To be diagnosed with ADHD, a patient
must display the symptoms for at least six months and not have related disorders,
which could be contributory or a direct cause of the symptoms. The precise cause
of the condition is unknown, although it is believed to be related to the rapid
metabolism of dopamine and to a lesser extent norepinephrine, both of which
are synaptic neurotransmitters.
The bulk of the products on the market, which include Ritalin
from Novartis (SWX:NOVN, Basel, Switzerland), Methylin from Mallinckrodt Inc.
(MKG, St. Louis, Mo.), and Concerta from Alza (AZA, Mountain View, Calif.),
are based on methylphenidate. The mechanism of action of methylphenidate also
is not fully understood, but it is believed to increase the output of both dopamine
The other marketed products are from Shire Pharmaceuticals
Group plc (LSE:SHP; SHPGY, Andover, U.K.). Its Adderall is mixed salts of amphetamine
while DextroStat is a single salt of amphetamine. Amphetamine is an adrenergic
Other drugs besides stimulants are used to treat ADHD, including
GlaxoWellcome's Wellbutrin (bupropion), a weak blocker of the neuronal uptake
of norepinephrine that also inhibits to some extent the neuronal reuptake of
dopamine. But they have drawbacks, such as a long onset of action and concerns
about safety - bupropion lowers the seizure threshold in a dose-related fashion.