By Toni Clarke
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."
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.
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.
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.)