Public health officials have focused attention on the staggering increase in opioid overdoses and abuse of prescription painkillers, but little has been said about another growing threat -- abuse of drugs used to treat attention deficit/hyperactivity disorder (ADHD) in adults.
Since 2013, the FDA has received 19,000 reports of complications from ADHD drugs, most of which are stimulants like Adderall (amphetamine and dextroamphetamine), Concerta (methylphenidate), Ritalin (methylphenidate), and Vyvanse (lisdexamfetamine), according to a Milwaukee Journal Sentinel/MedPage Today analysis.
Of those, adults were far more likely than children to suffer severe complications, such as death and hospitalization.
Among those age 26 or older, recreational use of Adderall, rose almost four-fold, from 345,000 people in 2006 to 1.4 million in 2014, according to the latest available federal data.
In emergency departments around the country, the number of cases involving two common ADHD drugs -- Adderall and Ritalin -- quintupled over 7 years.
In Florida, a bellwether state for drug abuse problems, overdose deaths involving stimulants increased more than 450% between 2008 and 2014.
Taken together, the data show the drugs -- which have been heavily promoted by the pharmaceutical industry -- left a trail of misuse, addiction and death, a Journal Sentinel/MedPage Today investigation found.
Something Happening Here
Twenty years ago, adult ADHD was a seldom-diagnosed disorder.
But this diagnosis is now common in mainstream medicine, a paradigm shift that appears to be driven by two factors: reworked -- many say less stringent -- diagnostic criteria, and marketing by makers of these drugs, one of which helped fund a study that claimed 1 out of 23 adult Americans are affected by the condition, which would put the adult ADHD population at roughly 10 million.
"The streets are awash with Adderall," said Nicolas Rasmussen, PhD, MPH, a medical historian who has studied the history of amphetamines in the U.S. "Amphetamines are grossly overused."
Other critics question whether adult ADHD truly is truly a widespread condition requiring treatment with potent drugs.
It is among several conditions identified by Journal Sentinel and MedPage Today in which diagnostic definitions were expanded -- the bar lowered -- to create a larger market for treatment with expensive, often dangerous drugs. In many instances the "evidence" proffered to expand those definitions came from research funded in whole or part by the pharmaceutical industry.
In the case of adult ADHD, the definition was relaxed in 2013 by the American Psychiatric Association. Under the new definition, adults need to have five of nine possible symptoms from either of two categories, down from six of nine, and the symptoms must have been present before age 12. The earlier definition required symptoms to be present prior to age 7.
Of the experts on the panel that approved the changes, 78% had financial ties to drug companies, according to a 2012 analysis published in the journal PLoS Medicine.
In a Journal Sentinel/MedPage Today investigation published in May, Darrel Regier MD, MPH,an APA spokesman said financial conflicts of interest among panel members were limited to $10,000 a year, which included funds received for work as industry speakers and consultants. The $10,000 limit is one commonly used -- and just as commonly criticized -- by organizations promulgating guidelines.
Regier also defended inclusion of the adult ADHD definition in the APA's diagnostic manual, saying that even though ADHD once was thought to be a childhood condition, for some, it remains in adulthood.
Industry Responds
Spokespersons for drug companies say adult ADHD is a real and treatable medical condition affecting millions of Americans.
Jessica Castles Smith, a spokesperson for Janssen Pharmaceuticals, which makes the ADHD drug Concerta, said the company continually monitors the safety and effectiveness of its drug in cooperation with the FDA. She said any new data are incorporated into the product's label so that doctors and patients can make informed decisions.
"All medicines, including Concerta, have both benefits and risks," she said.
Charlie Catalano, a spokesman for Shire, which makes the ADHD drugs Adderall and Vyvanse said it has been approved by regulators around the world based on an acceptable benefit-risk profile.
"Our medications are proven to be effective when used according to prescribing practices of a licensed, trained healthcare professional," he said.
Eric Althoff, a spokesperson for Novartis, which makes Ritalin, said their drug "has been used safely and effectively for more than 60 years." Given that Ritalin has been used "for decades, the labeling [information] reflects the safety data gathered over years of experience," he said.
He noted that "if used inappropriately, the results could be serious, just like with the misuse of any other medication."
"Soft" Symptoms
The symptoms of the condition typically involve an inability to focus on tasks, fidgeting, or interrupting others. Experts note the symptoms are vague, can be caused by other conditions, and are easy to fake.
One study published in 2010 found that 22% of adults tested for ADHD had exaggerated their symptoms.
For years, the legitimacy of adult ADHD was based on the belief that for some it was a condition that started in childhood and persisted into adulthood.
But that belief was undermined last year, when researchers published the results of a long-term study that began in the early 1970s and followed more than 1,000 New Zealand children until age 38. The study found little overlap between those who had ADHD as children and those who were diagnosed as adults.
While none of the symptoms are life-threatening, the drugs approved by the FDA to treat adult ADHD can raise heart rates and blood pressure, and have been linked to sudden cardiac death. They also carry a high potential for abuse and dependence.
The long-term risks and benefits in adults are not known. Drugs often are tested for a year or more, but rigorous clinical trials of ADHD drugs on adults have not lasted more than a few weeks or months.
Among the adverse events reported to the FDA:
- A 41-year-old woman was hospitalized with kidney failure after abusing methylphenidate, the stimulant in Ritalin.
- A fatal heart attack in a 41-year-old man with known heart disease who was taking two ADHD drugs as well as atorvastatin and losartan.
- A 33-year-old man on the ADHD drug Vyvanse was hospitalized after suffering a panic attack, an increased heart rate, chest pain, and dizziness.
The Journal Sentinel/MedPage Today analysis of the FDA data focused only on adverse event reports from healthcare professionals and drug companies, both of which are required to file adverse event reports. The FDA also collects patient reports, but this analysis does not include patient reports.
James Stein, MD, a cardiologist at the University of Wisconsin, said he has treated adult patients who developed serious problems after being misdiagnosed with ADHD and put on prescription stimulants.
One patient developed extremely high blood pressure; another developed an irregular heartbeat, he said.
Stein said he worries about the increase in prescriptions and marketing of ADHD drugs to patients.
"I don't think these are the kinds of drugs that should be thrown around willy nilly," Stein said.
More Prescriptions, More Problems
Between 2010 and 2015, sales of ADHD drugs jumped from $7.9 billion to $11.2 billion, according to data from IMS Health, a drug market research firm. Prescriptions increased from 67 million to 87 million.
The surge came on the heels of a pattern starting in 2008 in which prescriptions written for adults jumped 53% over 4 years, according to Express Scripts, a national prescription benefit plan provider.
Those numbers only tell part of the story:
- In the last decade, the U.S. Drug Enforcement Administration authorized increased production of legal methylphenidate, the stimulant in Ritalin, from 38 tons to nearly 106 tons.
That's enough to provide every man, woman and child in America with 30 tablets of Ritalin -- a month's supply.
- In Tacoma, Wash., the presence of amphetamines in wastewater samples collected near college dormitories was eight times higher during final exams week than the first week of classes, according to a 2013 study.
- On the user-driven website Reddit, nearly 5,000 readers share tips on abusing the drug Adderall, ranging from how to convince doctors to write a prescription to dealing with skin outbreaks from snorting the drugs.
Rasmussen, the medical historian who has studied amphetamines, said the drugs are prone to abuse because "people often feel it makes their lives better. It's an antidepressant, it offers weight loss, and it improves confidence."
"Someone might start out with methylphenidate or Vyvanse, but then their tolerance builds and they want more," he said.
While opioids are more lethal than prescription stimulants, some experts see parallels between the opioid epidemic and the increase in problems tied to stimulants.
In the opioid epidemic, users switched from prescription narcotics to heroin and illicit fentanyl. With the ADHD drugs, patients are switching from legally prescribed stimulants to illicit ones, such as methamphetamine and cocaine.
Some say the similarities extend to loose criteria for diagnosing the underlying condition and the large number of prescription drug options -- more than a dozen in the case of ADHD. The relaxed definition of adult ADHD also has played a role.
"Doctors get more patients; patients have their symptoms 'medically explained,' and pharma has a new group of people to use their medications," said Lewis Nelson, MD, chair of emergency medicine at Rutgers New Jersey Medical School. "Clearly it becomes a cat and mouse game of new diagnoses begetting new drugs."
Petros Levounis, MD, chair of psychiatry at Rutgers, said he saw an increase in people seeking help for stimulant addiction when he opened a treatment center aimed at college students.
Levounis said he believes ADHD is poorly understood, which leads to both under- and over-treatment.
In some cases, people who need treatment don't seek help, he said. Other times, doctors are quick to diagnose ADHD when other conditions are causing the problems.
"Medicine has a huge responsibility with what happened with the prescription opioid epidemic," Levounis said. "If there is something brewing with prescription stimulants, we should be doubly, triply concerned about it."
Overdoses and deaths involving prescription stimulants are not tracked by any one government entity. To assess the scope of the adult ADHD drug problem, the Journal Sentinel and MedPage Today examined data from federal, state, and municipal authorities.
Reports to the FDA
The analysis of FDA adverse event reports showed most problems occurred in children, for whom ADHD has long been a common diagnosis. But when adults did report problems, they were more likely to be the most serious.
Adults accounted for just over one-third of reports, but made up more than half of all hospitalizations and nearly 85% of deaths.
Users reported several psychological problems. Hallucinations, suicidal thoughts, and depression show up in hundreds of reports. Quitting the drugs also posed a problem, as several reports indicated withdrawal symptoms.
Except for atomoxetine (Strattera), nearly all adult ADHD drugs are stimulants. That drug has not been shown to lead to abuse, but carries the FDA's most stringent warning because it can create suicidal thoughts in children and adolescents.
Adults are warned that it can cause serious cardiovascular problems, including strokes, heart attacks, and sudden death.
Emergency Department Visits
In 1972, the Drug Enforcement Administration set up a system to monitor emergency room visits caused by drug abuse. Though the program, known as the Drug Abuse Warning Network, stopped collecting data in 2011, in its final years a rise in stimulant-related visits stood out.
In 2004, just two ADHD drugs played a role in 10,800 emergency department visits. By 2011, the figure jumped to 42,000, a nearly fourfold increase in less than a decade.
The increase involved methylphenidate, the stimulant in Ritalin, and amphetamine/dextroamphetamine, the stimulant in Adderall.
Increasingly, adults were affected. In 2004, the number of emergency amphetamine/dextroamphetamine-related visits in those age 25 and older was so low it couldn't be estimated. By 2011, 10,000 25- to 44-year-olds went to emergency rooms after using the drug.
In the 5 years since the tracking program ended, the U.S. Drug Enforcement Administrationapproved a 60% increase in amphetamine production and the number of prescriptions for ADHD drugs jumped 20%.
The tracking ended due to a lack of funding, said Elizabeth Crane, an analyst at the Substance Abuse and Mental Health Services Administration, which last oversaw the program.
"It was unfortunate timing," she acknowledged.
Death Reports
The CDC does not separate overdose deaths caused by prescription stimulants from those due to illicit stimulants.
Still, the number of deaths in the overall category increased by 22%, on average, every year since 2008. In 2014, the most recent year available, there were 5,100 deaths.
Other data suggest that deaths attributed to prescription stimulants demonstrated a significant spike. While a few of the drugs can be used to treat conditions such as narcolepsy and binge-eating disorder, the most stimulants are prescribed for ADHD.
In Florida, medical examiners cited amphetamine use in 1,318 cases from 2008 to 2014, ruling that prescription amphetamines contributed to 277 deaths.
In 2008, the drugs led to 12 deaths. In 2014, reports peaked at 67 deaths.
Final Analysis
If that rate were applied to the nation, it would mean there were more than 1,000 deaths from prescription stimulants in 2014.
Preliminary data indicate a substantial increase in deaths in Florida again in 2015.
"It looks to me like it's an under-the-radar epidemic," said psychiatrist Ken Duckworth, MD, medical director of the National Alliance on Mental Illness. "It's a real phenomenon."