2012-01-02 10:28:14
By Toni Clarke | Reuters
BOSTON (Reuters) - A shortage of Adderall, which is used to treat attention
deficit hyperactivity disorder, shows little sign of easing as manufacturers
struggle to get enough active ingredient to make the drug and demand climbs.
Adderall, a stimulant, is a controlled substance, meaning it is addictive and
has the potential to be abused. The Drug Enforcement Administration tightly
regulates how much of the drug's active pharmaceutical ingredient (API) can be
distributed to manufacturers each year.
The system is designed to prevent the creation of stockpiles that could be
diverted for inappropriate use. Adderall and other stimulants are popular with
students who may not have ADHD but are seeking to improve their test scores.
The DEA authorizes a certain amount of the API in Adderall - mixed amphetamine
salts - to be released to drugmakers each year based on what the agency
considers to be the country's legitimate medical need.
Increasingly that estimate is coming into conflict with what companies
themselves say they need to meet demand for the drug, which is reaching
all-time highs. In 2010, more than 18 million prescriptions were written for
Adderall, up 13.4 percent from 2009, according to IMS Health, which tracks
prescription data.
Concerns are now rising among patient groups and doctors that the shortages
seen in 2011 will continue into this year. Many orders remain unfilled,
manufacturers say, and it may take several months before ingredient authorized
under the new 2012 quota can be turned into new product.
"I am very concerned about the future," said Ruth Hughes, chief executive of
Children and Adults with Attention Deficit/Hyeractivity Disorder (CHADD). "No
one seems to have much inventory to get us through the months ahead."
ADHD is one of the most common childhood disorders. An average of 9 percent of
children between the ages of five and 17 are diagnosed with ADHD per year,
according to the Centers for Disease Control and Prevention.
Symptoms include difficulty staying focused, hyperactivity and difficulty
controlling behavior. If they are not properly medicated, children with ADHD
may act out and be held back in class; adolescents might engage in impulsive,
risky behavior; adults are at greater risk of being fired from their jobs.
"There are real major life impacts for people not having access to medication,"
Hughes said. "Someone needs to own this problem and take the initiative to fix
it."
RIPPLE EFFECT
Adderall is made in several dosages and formulations. Shire Plc makes Adderall
XR, a more expensive extended release version of the drug. Authorized generic
versions of Adderall XR are sold by Teva Pharmaceutical Industries and Impax
Laboratories Inc.
Shorter-acting instant release forms are made by Sandoz, a unit of Swiss
drugmaker Novartis AG, as well as by CorePharma LLC and Teva. It is the
shorter-acting versions of the drug that are currently in shortest supply.
The full scope of the shortage is unclear. Patients have been scrambling since
mid-year to find pharmacies carrying the drug. Some have been switched to other
medications such as Adderall XR or Ritalin, a rival drug known also as
methylphenidate. But companies do not always track which pharmacies have their
product at any given time.
"We don't monitor the distribution system, but we do know that all our
customers are on back order right now," said Teva spokeswoman Denise Bradley.
Teva sells to wholesalers and distributors as well as to some hospitals and
specialty pharmacies - and all have orders placed but not filled.
Hughes said CHADD, along with the American Academy of Child and Adolescent
Psychiatry, another advocacy organization, has recently started to track where,
geographically, the calls about shortages are coming from.
Quantifying the problem is particularly urgent since the Adderall shortage is
now also spilling over and causing shortages of Ritalin. Sandoz, which makes
generic forms of both drugs, is straining to meet increased demand for both
products.
"There is currently not enough product to fill all of our customer orders at
the wholesaler level," said Julie Masow, a spokeswoman for Novartis, in an
email.
TENSIONS FLARE
The problem is particularly troublesome since no one really agrees on its
cause.
Under the quota system, drugmakers receive enough material to meet what the DEA
estimates will meet the legitimate needs of American patients, but not enough
to build inventory. The DEA says recent shortages were not caused by an
insufficient quota but by marketing decisions taken by the companies.
"Any shortage of these products is therefore a result of decisions made by
industry regarding manufacturing or distribution," Barbara Carreno, a DEA
spokeswoman said, though she declined to specify those decisions.
She noted that there are currently more than 200 drugs in short supply in the
United States, most of which do not contain controlled substances and have
nothing to do with the DEA.
"There is no reason to think that the same market forces that are causing those
shortages are not playing a part in these," Carreno said.
President Barack Obama recently issued an executive order demanding that the
Food & Drug Administration address these shortages, which mostly affect generic
injectable drugs that companies are no longer making as they are not as
profitable as newer products.
For their part, Adderall manufacturers say they are working flat out to meet
demand, and say the DEA does not always approve enough material in time for
them to supply customers.
"Our production facilities are currently running at maximum capacity for
Adderall utilizing all available API," said Teva's Bradley. "The catalyst for
the problem is the quota system, not the business."
The DEA sets its aggregate quota at the beginning of each year, taking into
account past quota levels, inventory levels and company sales forecasts. But
the DEA's assessment of what a company needs may not be the same as the
company's own estimates. It is an ongoing process of negotiation.
"DEA can come back and say, 'we agree with your forecast and issue everything
you want,' or they may come back and say 'we don't think you need that much,'
and they give you 75 percent," said Matt Cabrey, a spokesman for Shire.
Early last year, Shire suffered shortages of Adderall XR. "It was directly
related to the API quota," Cabrey said. In June 2010, Shire calculated that API
was running too low. It applied to the DEA for more, but did not receive the
additional supply until December. It typically takes Shire three months to then
make the product and get it to customers.
As a result, Cabrey said, there were shortages of Adderall XR in January and
February last year and supplies did not return to normal until March and April.
The company said there are no shortages of Adderall XR, though some patients
say even that is now hard to get hold of.
Amy Alkon, 47, who writes a syndicated column on dating and manners, began
taking Adderall for her ADHD about five months ago after Ritalin stopped
working for her. This week she spent hours on the phone trying to find a
pharmacy that could fill her prescription - and she couldn't find Adderall or
Adderall XR.
"I have gone to the biggest medical centers in the Los Angeles area, I've
called countless pharmacies and they have no pills," she said. "Nobody has
anything."
For Alkon, the prospect of the shortage continuing is alarming. Adderall, she
said, has changed her life, allowing her to organize her thoughts and tamp down
what she calls a "tornado" of activity in her brain.
CONTROLLED SUBSTANCES
The DEA, while insisting its quota for 2011 was sufficient, nonetheless revised
it upwards in December.
"We increase the aggregate so that we will have enough to respond to specific
companies if their requests for more amphetamine salts are justified and
needed," said Carreno. "The companies can and do request more amphetamine
salts, and we can and do respond to those requests throughout the year."
Simply increasing the overall national quota, however, does not address company
complaints that it takes DEA months to approve individual requests for new
product.
Asked why it might take the agency months to approve a company's request, the
DEA said it is required by law to balance providing enough API to meet the
legitimate needs of patients while protecting the public from any diversion of
potentially lethal substances.
"We do our best to accomplish both missions, and the quota system is part of
the process for achieving this," Carreno said.
That is not good enough for CHADD's Hughes or other advocacy groups, who plan
to lobby both the DEA and drugmakers to find a solution to the shortages.
"When you have a controlled substance problem, the DEA has to be involved in
fixing it," said Hughes. "It is not sufficient to say it is an industry
problem. We need to figure out how to build more flexibility into the system."
The DEA controls roughly 400 basic substances, in addition to derivative
products such as salts and ethers.
The chemicals are divided into five schedules. Schedule 1 drugs include illegal
substances such as heroin. Scheduled II drugs, such as Adderall and other
stimulants, have a medical use but a high potential for abuse. Schedule III
drugs have a somewhat lower abuse potential and include the painkiller Vicodin,
while Schedule IV drugs include the tranquilizers Klonopin and Ativan. Schedule
V substances include cough medicines such as Robitussin.
Adderall is popular on college campuses, even among those who do not have ADHD
but want a performance boost. Students may trade the drug or get it from their
siblings or parents.
Stimulants appear to work in patients with ADHD by increasing the availability
in the brain of the chemicals dopamine and norepinephrine, which both appear to
help regulate attention and executive function. Their effects differ slightly
depending on the drug, and some people respond better to one than another.
"In every suburban high school and in colleges there is a significant
underground economy around stimulants," said Harry Tracy, a psychologist and
publisher of NeuroPerspective, a monthly publication focusing on central
nervous system disorders. "Adderall can go for $5 to $10 a pop."
Physicians say it can be challenging to sort out who is a legitimate patient
and who might seek the drug simply to enhance performance.
"Trying to determine the best thing to do can be a quandary at times because
there is this question of whether the person is trying to get the medication
for nonmedical reasons," said Steven Cuffe, a child psychiatrist and Chairman
of the Department of Psychiatry at the University of Florida College of
Medicine.
Right now patients are trying to scrape by, either by traveling long distances
to fill prescriptions or switching to other products even if they don't work as
well or are more expensive. But these are temporary workarounds and without a
structural change manufacturers and advocate groups fear the problem will
linger or even worsen.
"This does not seem to be a short-term solvable problem," Hughes said.
(Additional reporting by Ransdell Pierson and Lewis Krauskopf in New York,
Jessica Wohl in Chicago; Editing by Michele Gershberg, Martin Howell in New
York.)