Meta-analysis confirms common painkillers increase risk of heart problems and death

NSAIDs have been the cornerstone in managing pain in people with inflammatory disorders like rheumatoid arthritis, and are some of the most commonly used drugs worldwide. Earlier research has linked their use with an increased risk of serious gastrointestinal complications, while a new generation of NSAIDs (coxibs) developed to reduce these gastrointestinal side effects have come under scrutiny for increasing the risk of heart attacks and death.

30 may 2013--This new study now shows that higher dose regimens of older NSAIDs, such as diclofenac 150mg and ibuprofen 2400mg daily, are associated with similar risks of heart disease.

As such, for every 1000 individuals with a moderate risk of heart disease allocated to 1 year of treatment with high-dose diclofenac or ibuprofen, about three would experience an avoidable heart attack, of which one would be fatal.

In addition, all NSAIDs double the risk of heart failure and produce a 2-times increased risk of serious upper gastrointestinal complications such as bleeding ulcers.

The Coxib and traditional NSAID Trialists' (CNT) Collaboration combined data on outcomes of over 353 000 patients comparing one NSAID with another NSAID or placebo.

The meta-analysis of patient data from 639 randomised trials shows that the size of these risks can be predicted, which may help physicians decide which types of patient are best suited to which NSAID regimen.

Importantly, the increased risk of heart attacks from individual NSAIDs seemed to be proportional to a patient's underlying risk of such heart attacks, so that the risk is highest in those with a previous history of heart disease or those with cardiac risk factors such as raised blood pressure or cholesterol.

According to lead author Professor Colin Baigent from the Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, UK, "Whilst NSAIDs increase vascular and gastrointestinal risks to a varying extent, our analyses indicate that the effects of different regimens in particular patients can be predicted, which may help physicians choosing between alternative NSAID regimens to weigh up which type of NSAID is safest in different patients."

Writing in a linked Comment, Marie Griffin from Vanderbilt University Medical Center in the USA says, "The meta-analysis offers considerable certainty about relative and absolute major vascular risks of high doses of the most commonly prescribed NSAIDs, but leaves large gaps about risks associated with lower NSAID doses, longer durations of use, and residual effects after stopping treatment."

She adds, "Identification of safe and effective strategies for chronic pain is sorely needed. In the meantime, long-term use of high dose NSAIDs should be reserved for those who receive considerable symptomatic benefit from the treatment and understand the risks."

More information: www.thelancet.com/… 0-9/abstract

Provided by Lancet

Methadone Rises as a Painkiller With Big Risks

By ERIK ECKHOLM and OLGA PIERCE
18 aug 2008--Suffering from excruciating spinal deterioration, Robby Garvin, 24, of South Carolina, tried many painkillers before his doctor prescribed methadone in June 2006, just before Mr. Garvin and his friend Joey Sutton set off for a weekend at an amusement park.
On Saturday night Mr. Garvin called his mother to say, “Mama, this is the first time I have been pain free, this medicine just might really help me.” The next day, though, he felt bad. As directed, he took two more tablets and then he lay down for a nap. It was after 2 p.m. that Joey said he heard a strange sound that must have been Robby’s last breath.
Methadone, once used mainly in addiction treatment centers to replace heroin, is today being given out by family doctors, osteopaths and nurse practitioners for throbbing backs, joint injuries and a host of other severe pains.
A synthetic form of opium, it is cheap and long lasting, a powerful pain reliever that has helped millions. But because it is also abused by thrill seekers and badly prescribed by doctors unfamiliar with its risks, methadone is now the fastest growing cause of narcotic deaths. It is implicated in more than twice as many deaths as heroin, and is rivaling or surpassing the tolls of painkillers like OxyContin and Vicodin.
“This is a wonderful medicine used appropriately, but an unforgiving medicine used inappropriately,” said Dr. Howard A. Heit, a pain specialist at Georgetown University. “Many legitimate patients, following the direction of the doctor, have run into trouble with methadone, including death.”
Federal regulators acknowledge that they were slow to recognize the dangers of newly widespread methadone prescribing and to confront physician ignorance about the drug. They blame “imperfect” systems for monitoring such problems.
In fact, a dangerously high dosage recommendation remained in the Food and Drug Administration-approved package insert until late 2006. The agency has adjusted the label and is now considering requiring doctors to take special classes on prescribing narcotics.
Between 1999 and 2005, deaths that had methadone listed as a contributor increased nearly fivefold, to 4,462, a number that federal statisticians say is understated since states do not always specify the drugs in overdoses. Florida alone, which keeps detailed data, listed methadone as a cause in 785 deaths in 2007, up from 367 in 2003. In most cases it was mixed with other drugs like sedatives that increased the risks.
The rise of methadone is in part because of a major change in medical attitudes in the 1990s, as doctors accepted that debilitating pain was often undertreated. Insurance plans embraced methadone as a generic, cheaper alternative to other long-lasting painkillers like OxyContin, and many doctors switched to prescribing it because it seemed less controversial and perhaps less prone to abuse than OxyContin.
From 1998 to 2006, the number of methadone prescriptions increased by 700 percent, according to Drug Enforcement Administration figures, flooding parts of the country where it had rarely been seen.
But too few doctors, experts say, understand how slowly methadone is metabolized and how greatly patients differ in their responses. Some prescribe too much too fast, allowing methadone to build to dangerous levels; some fail to warn patients of the potential dangers of mixing methadone with alcohol or sedatives, or do not keep in contact during the perilous initial week on the drug. And some patients do not follow the doctor’s orders.
“Those problems were not soon recognized,” said Dr. Bob Rappaport, a division director at the Food and Drug Administration. He added: “Methadone is an extremely difficult drug to use, even for specialists. People were using it rather blithely for several years.”
Dr. James Finch, an addiction specialist in Durham, N.C., said, “In the clinical and regulatory communities, everyone is trying to run and catch up with and deal with the causes of methadone overdoses.”
This year the federal government started sponsoring voluntary classes that teach doctors the elaborate precautions they should take with methadone, like inching upward from low starting doses and screening patients for addictive behavior. (While Robby Garvin’s doctor could argue that the dosage he was taking was reasonable — one to two 10-mg tablets, three times a day — and he was cleared by his state medical board, many specialists would have started him on a lower dose.)
In what critics call a stunning oversight, the F.D.A-approved package insert for methadone for decades recommended starting doses for pain at up to 80 mg per day. “This could unequivocally cause death in patients who have not recently been using narcotics,” said Dr. Robert G. Newman, former president of Beth Israel Medical Center in New York and an expert in addiction.
The F.D.A. says that in the absence of reports of problems by doctors or surveillance systems, “we would have no reason to suspect that the dosing regimen” might need to be adjusted.
In November 2006, after reports of overdoses and deaths among pain patients multiplied and The Charleston Gazette reported on the dangerous package instructions, the F.D.A. cut the recommended starting limit to no more than 30 mg per day. “As soon as we became aware of deaths due to misprescribing for pain patients, we began the process of instituting label changes,” Dr. Rappaport said.
Methadone, which is made by Roxane Laboratories Inc. of Columbus, Ohio, and Covidien-Mallinckrodt Pharmaceuticals of Hazelwood, Mo., creates dependency and is sometimes sought by abusers who say they experience a special buzz when mixing it with Xanax.
While the greatest numbers of methadone-related deaths have occurred among the middle-aged, the fastest growth — an elevenfold jump between 1999 and 2005, to 615 — occurred among those age 14 to 24, which experts say may be mainly a result of pill abuse.
Pain experts say the country is seeing a reprise of the abuse and tragedies that followed the introduction of OxyContin, a time-release form of oxycodone that was heavily marketed in the late 1990s. It became a factor in hundreds of deaths and a focus of law enforcement.
OxyContin is still widely prescribed, but a survey of Medicare plans in 2008, by the research firm Avalere Health LLC, found that many did not even include OxyContin on the list of reimbursable drugs. Critics like Dr. June Dahl, professor of pharmacology at the University of Wisconsin, fault the insurance companies for favoring methadone simply because of its monetary cost. “I don’t think a drug that requires such a level of sophistication to use is what I’d call cheap, because of the risks,” Dr. Dahl added.
Yet for the right patients, methadone can be a godsend. Alexandra Sherman, a patient of Dr. Heit’s at his Fairfax, Va., clinic, suffered for years from hip and shoulder pain that “felt like somebody stabbing me with a knife,” she said. Pain began to rule and ruin her days.
Dr. Heit gave her OxyContin and later, because it seemed to work better and because of the expense, switched her to methadone. Her insurance at one point covered only $500 in prescriptions, which paid for just one month’s worth of OxyContin, compared with methadone’s cost of $35 a month.
Methadone “has given me my life back,” Ms. Sherman said.
But Dr. Heit did not just throw drugs at her problem. He told her that she would also have to try physical therapy as well. They signed a contract listing mutual obligations — she would follow directions, he would be on call. He starts patients at low doses, makes them bring in their pill bottles so he can count how many are left, and may give urine tests to deter mixing drugs.
Some doctors, like Dr. Theodore Parran of Case Western Reserve University, also require methadone patients to give them the names of relatives or friends they can call from time to time.
But not all doctors have taken such precautions. Tony Davis, a contractor in Victorville, Calif., had just turned 38 in 2004 when, after years of migraines and back pain, he saw a new pain doctor in his Kaiser Foundation Health Plan. The doctor, who had already given him the sedative Xanax, prescribed methadone because of his continued pain.
The second day on the two medications, Mr. Davis said, “I’m feeling really weird,’ ” recalled his wife, Pebbles Davis. The two lay down for a nap and when she woke up, her husband was dead.
Ms. Davis recalled that the coroner had told her, “Given the medicines he was on, his brain forgot to tell his heart to beat and his lungs to pump.” The case went to an arbitrator, who ruled that although Mr. Davis had overused his drugs in the past, the doctor had failed to warn him about the new risks of starting methadone together with Xanax and that the care was substandard. Ms. Davis was awarded more than $500,000. “I never had any idea of the risk nor did my husband,” she said.
Another source of danger has been the conversion tables that doctors use when switching patients from one opioid to another — telling, for example, how many milligrams of methadone would be equivalent to the level of morphine a patient had been taking. These charts, until recently, indicated dangerously high doses for methadone. Newer ones suggest lower levels but many experts say these may be useless because methadone affects patients so variably.
Now, as the government is making new efforts to teach methadone’s challenges, some officials and doctors would go further, requiring prescribers to take a course before using methadone.
But many physicians and patient groups are wary of any steps that would slow access to pain treatments.
As early as 2003, alarmed by the rise in methadone-related deaths, the Substance Abuse and Mental Health Services Administration made an urgent call for more systematic and detailed state and national reporting about opioid deaths — a call that still goes unanswered.
Misuse by abusers was first seen as the problem, but now, said Dr. H. Westley Clark, director of the Center for Substance Abuse Treatment of SAMHSA, “We know that a significant share of the methadone deaths involve doctors making well-intended prescriptions.”
A majority of victims also used large quantities of alcohol or benzodiazepine sedatives but few would have died without an opioid as the primary culprit. “You can take a lot of benzodiazepines without dying,” said Dr. Charles E. Inturrisi of Weill Cornell Medical Center, who said they strengthen the depressive effect of methadone.
Some doctors prescribe to patients who may be expected to court danger, like Anna Nicole Smith, who died from a drug cocktail including methadone.
Last February, Margaret Moore, 54, who lived alone in South Pasadena, Fla., with a history of alcoholism, depression and chronic back pain from a car accident, was found dead at home. Her doctor had prescribed methadone and valium and, he told investigators, warned her to stop drinking.
Her body was surrounded by empty vodka bottles and a host of pills including bottles of methadone tablets and sedatives. Her death was declared an accident from methadone toxicity.
Since April, SAMHSA has sponsored nine voluntary training courses on the safe prescribing of opioids, and many more are planned, though they will only reach a fraction of prescribers. The agency is also contracting with the American Society on Addiction Medicine to set up a mentoring program, through which prescribing physicians can receive expert advice. The State of Utah has a plan to educate every doctor and pain patient in the state about safe use of methadone and other opioids.
Nancy Garvin, Robby’s mother, is one of many relatives of victims who, in the absence of a national registry, have started educational and pressure groups to fight bad prescribing and abuse of the drug.
Still, the death rate appears to be rising, raising the question of what more may be necessary, in law enforcement and in doctor training.
“Methadone can be important for patients when other drugs don’t work,” said Dr. Inturrisi, ”but unless the doctor has the training and resources to manage the patient properly, he’s going to get in trouble at a rate that’s unacceptable.”

Pain Medicines and Immunomodulators Top List of Drugs With Adverse Events

HUNTINGDON VALLEY, Pa., Sept. 10 -- Reports of drug-related injury, disability, and death sent to the FDA nearly tripled during an eight-year period beginning in 1998, according to an analysis of agency data.
A minority of drugs-usually painkillers and immune modulators-- accounted for a majority of adverse events reports, according to a study in the Sept. 10 issue of Archives of Internal Medicine, but only a modest number were related to drugs such as rofecoxib (Vioxx), which were withdrawn because of safety concerns.
Thomas J. Moore, A.B. of the Institute for Save Medication Practices here, and colleagues at Wake Forest analyzed all serious adverse drug events and medication errors reported to the FDA from 1998 through 2005. During that time the reports of serious adverse events increase from 34,966 to 89,842 and reports of fatal events increased form 5,519 to 15,107.
Among the most frequently reported drugs there was a disproportionate contribution of pain medications and drugs that modify the immune system, they reported.
For example, oxycodone was suspected in 5,548 deaths, ranking it number one of 15 drugs linked to mortality. By contrast, rofecoxib was suspect in 932 deaths and ranked number 14.
Estrogen, which was linked to 11,514 reports of serious injury or disability, earned the number one rank in that category followed by insulin with 9,597 reported adverse events. Inflixmab (8,754 events), interferon beta (8,320), and paroxitine (8,095) were ranked third, fourth, and fifth followed in sixth place by rofecoxib, which was linked to 7,766 events.
The authors sought to limit the impact of well-publicized drug withdrawals by excluding adverse event reports received more that 14 days after events such as the withdrawal of rofecoxib in September 2004.
But even if the authors had included those reports, they would have accounted for fewer than 10% of all reported events and the number of reports associated with recalled drugs declined since 1999, they wrote.
The rate of increase in reports of adverse events and deaths actually outstripped the growth in prescriptions-growing at a rate that was four times faster than the growth in prescriptions, Moore and colleagues wrote.
Among the findings:
A minority of reports, 19.1% were made directly to the FDA, while 67.2% came to the FDA via the drug makers.
Doctors and other health professionals filed more than 70% of all adverse event reports and 82% of the fatal event reports.
17.3% of reports involved a death outcome, 7% indicated permanent disability or birth defect and 75.7% represented serious outcomes.
Most of the reports involved women (55.5%) and 33.6% of reports involved adults ages 65 or older.
A total of 1,489 drug products were named in adverse event reports, but 298 drugs accounted for 87.1% of reported events.
The number of serious adverse events associated with anti-tumor necrosis factor, interferon alpha, and interferon beta products rose 15.8 -fold from 1998 through 2005.
The study was limited by its reliance on the Adverse Event Reporting System, which is a collection of voluntary reports. Moreover, the submission of a report "does not establish causality," the authors cautioned.
Additionally, the authors "focused on only the primary suspect drug even though a median of two drugs per case were names and one quarter of the cases identified five or more drugs."
The authors concluded that rapid increase in the number of reports of drug-related adverse events "shows that the existing system is not adequately protecting patients and underscores the importance of recent reports urging far-reaching legislative, policy, and institutional changes."
Moore and his co-authors disclosed no financial conflicts and no funding source was disclosed. Primary source: Archives of Internal MedicineSource reference: Moore TJ "Serious Adverse Drug Events Reported to the Food and Drug Administration, 1998-2005" Arch Intern Med 2007; 167:1752-1759

Pain patients at risk for sleep apnea

Opioids associated with increased apnea risk
Opioid-based pain medications may cause sleep apnea, according to an article in the September issue of Pain Medicine, the journal of the American Academy of Pain Medicine.
“We found that sleep-disordered breathing was common when chronic pain patients took prescribed opioids,” explains lead author Lynn R. Webster, MD, from Lifetree Clinical Research and Pain Clinic in Salt Lake City, Utah. “We also found a direct dose-response relationship between central sleep apnea and methadone and benzodiazepines, an association which had not been previously reported.”
Opioids, effective medications for chronic pain treatment, are often used for cancer patients, but are now gaining widespread acceptance as long-term therapy for chronic pain unrelated to cancer. An increasing number of patients with nonmalignant chronic pain are receiving around-the-clock pain relief through opioid therapy.
The researchers studied sleep lab data on 140 patients taking around-the-clock opioid therapy for chronic pain to assess the potential and prevalence sleep apnea in opioid treated pain patients. All patients were on opioid therapy for at least six months with stable dosing for at least four weeks.
The investigators say that their results show a higher than expected prevalence of sleep disordered breathing in opioid treated chronic pain patients. Obstructive and central sleep apnea syndromes occurred in the studied population at a far greater rate (75%) than is observed in the general population, where obstructive sleep apnea is known to be underdiagnosed but has been estimated at roughly 2% to 4%. Central sleep apnea is estimated at 5% in people older than 65 years and from 1.5% to 5% in men less than 65 years old.
People who stop breathing during sleep because of faulty brain control have central sleep apnea as opposed to obstructive apnea, which is triggered by obesity and other health problems and accompanied by loud snoring.
The investigators comment that the absence of crescendo-decrescendo breath size commonly associated with central sleep apnea suggests that the central sleep apnea mechanism is different for people taking opioids than the general public. They suggest it could be related to the direct effects of opioids on the part of the brain that controls respiration.
The authors also note that if opioid medications increase sleep apnea risk as their research suggests, then chronic pain patients who are prescribed opioids have a higher risk of morbidity and mortality.
“The challenge is to monitor and adjust medications for maximum safety, not to eliminate them at the expense of pain management,” Dr. Webster concludes.
“The recent flurry of news reports of deaths associated with methadone use, and the synergy of opioids and benzodiazepines in causing respiratory depression, highlight the importance of Dr. Webster’s research. Clearly we need more studies of these mechanisms as well as ways of identifying those at risk. Doctors and patients who are considering opioid medication for pain control, must balance this risk against the potential for improved quality of life,” comments Rollin M. Gallagher, MD, Editor-in-Chief of Pain Medicine.

World of hurt: Painkiller use skyrockets

By Frank Bass, Associated Press
MYRTLE BEACH, S.C. — People in the United States are living in a world of pain and they are popping pills more than ever to cope with it.
The amount of five major painkillers sold at retail establishments rose 88% between 1997 and 2005, according to an Associated Press analysis of statistics from the Drug Enforcement Administration.
More than 200,000 pounds of codeine, morphine, oxycodone, hydrocodone and meperidine were purchased at retail stores during the most recent year represented in the data. That total is enough to give more than 300 milligrams of painkillers to every person in the country.
Oxycodone, the chemical used in OxyContin, is responsible for most of the increase. Oxycodone use jumped nearly six-fold between 1997 and 2005. The drug gained notoriety as "hillbilly heroin," often bought and sold illegally in Appalachia. But its highest rates of sale now occur in places such as suburban St. Louis; Columbus, Ohio; and Fort Lauderdale
The world of pain extends beyond big cities and involves more than oxycodone.
In Appalachia, retail sales of hydrocodone — sold mostly as Vicodin — are the highest in the nation. Nine of the 10 areas with the highest per-capita sales are in mostly rural parts of West Virginia, Kentucky or Tennessee.
Suburbs are not immune to the explosion.
While retail sales of codeine have fallen by one-quarter since 1997, some of the highest rates of sales are in communities around Kansas City, Mo., and Nashville, and on New York's Long Island.
The DEA figures analyzed by the AP include nationwide sales and distribution of drugs by hospitals, retail pharmacies, doctors and teaching institutions. Federal investigators study the same data trying to identify illegal prescription patterns.
An AP investigation found these reasons for the increase:
•The population is getting older. As age increases, so does the need for pain medications. In 2000, there were 35 million people older than 65. By 2020, the Census Bureau estimates the number of elderly in the U.S. will reach 54 million.
•Drugmakers have embarked on unprecedented marketing campaigns. Spending on drug marketing has gone from $11 billion in 1997 to nearly $30 billion in 2005, congressional investigators found. Profit margins among the leading companies routinely have been three and four times higher than in other Fortune 500 industries.
•A major change in pain management philosophy is now in its third decade. Doctors who once advised patients that pain is part of the healing process began reversing course in the early 1980s; most now see pain management as an important ingredient in overcoming illness.
James Fernandez, 54, of Fredericksburg, Va., survived two helicopter crashes and Gulf War Syndrome over 20 years in the Marine Corps. The retired staff sergeant remains disabled from his service-related injuries and takes the equivalent of nine painkillers containing oxycodone every day.
"It's made a difference," he said. "I still have bad days, but it's under control."
Such stories should hearten longtime advocates of wider painkiller use, such as Russell Portenoy, head of New York's Beth Israel pain management department. But they have not.
"I'm concerned and many people are concerned," he said, "that the pendulum is swinging too far back."
Consider:
• More people are abusing prescription painkillers because the medications are more available. The vast majority of people with prescriptions use the drugs safely. But the number of emergency room visits from painkiller abuse has increased more than 160% since 1995, according to the government.
• Spooked by high-profile arrests and prosecutions by state and federal authorities, many pain-management specialists now say they offer guidance and support to patients but will not write prescriptions, even for the sickest people. The increase in painkiller retail sales continues to rise, but only barely. There was a 150% increase in volume in 2001. Four years later, the year-to-year increase was barely 2%.
• People who desperately need strong painkillers are forced to drive a long way — often to a different state — to find doctors willing to prescribe high doses of medicine. Siobhan Reynolds, the widow of a New Mexico patient who needed large amounts of painkillers for a connective tissue disorder, said she routinely drove her late husband to see an accommodating doctor in Oklahoma.
Doctors eyed
Perhaps no place illustrates the trends and consequences for the world of pain better than Myrtle Beach, a sprawling community of strip malls, hotels and bars perched along a 60-mile strip of sand on the Atlantic Ocean. The metro area, which includes three counties, is home to 350,000 people but sees more than 14 million tourists annually, drawn to its warm water, golf courses and shopping.
During the eight-year period reflected in government figures, oxycodone distribution increased 800% in the area of Myrtle Beach, partly due to a campaign by Purdue Pharmaceuticals of Stamford, Conn. The privately held company has pleaded guilty to lying to patients, physicians and federal regulators about the addictive nature of their drug.
Use of other drugs soared in the area, too: Hydrocodone use increased 217%; morphine distribution went up 180%; even meperidine, most commonly sold as Demerol, jumped 20%.
It is no small wonder that federal authorities suspected the area was home to a notorious "pill mill," or a clinic that dispenses prescription medication without verifying that it's needed.
The U.S. attorney for South Carolina secured a 58-count indictment in June 2002 against seven physicians and one employee of the Comprehensive Care and Pain Management Center, a nondescript storefront on Myrtle Beach's main drag.
Tipped off by local pharmacists concerned about an increase in the volume of painkiller prescriptions, the federal investigation created a furor in the medical profession. The owner, D. Michael Woodward, was sentenced to 15 years in the case and has relinquished his license.
A second physician, Deborah Bordeaux, had worked at the clinic less than two months before quitting in disgust. Bordeaux, now serving a two-year prison term, was threatened with a 100-year sentence if she did not help the prosecution.
Officials with the Justice Department and the DEA would not discuss what some activists say is a "war on doctors."
Reynolds, the widow who drove her late husband hundreds of miles for his pills, became an activist after the Myrtle Beach indictments. She contributed money to appeal some of the criminal convictions in South Carolina and started the Pain Relief Network, an advocacy organization for people living in pain. She believes the doctors sent to prison were railroaded.
"It was a witch hunt," she said.
Bordeaux's husband, Edworth Swaim, agrees. A retired U.S. Postal Service employee, Swaim believes his wife was sentenced to two years because she would not turn on her former colleagues. Even though Bordeaux had worked at the clinic less than two months and eventually sued over what she alleged was rampant Medicare fraud, he said she did not stand a chance of avoiding prison.
"She wasn't guilty of anything, so she wasn't going to plead to anything," Swaim said. "She was absolutely railroaded, made an example of. I can't tell you how angry I am."
Myrtle Beach physicians are not convinced that the "Myrtle Beach Eight," as they became known, were innocent.
A Myrtle Beach internist who also works in addiction medicine, Brian Adler, said physicians were flooded with patients seeking pain medicine after the clinic was shut down.
The community has a slightly higher-than-average number of older people and relatively high numbers of people between 21 and 64 who describe themselves as disabled.
"There's a significant problem with narcotics in this area," Adler said. After the pain management clinic closed, "all those folks were like rats, scurrying from a burning building, trying to get their fix."
Other physicians were concerned about patients with legitimate needs for painkillers. The federal bust raised the stakes.
Abuse metrics lacking
When radio commentator Rush Limbaugh settled a federal case charging him with illegally obtaining painkillers, he did not get prison time. Neither did NFL star Brett Favre, who publicly acknowledged an addiction to Vicodin that he obtained legally.
To pain management specialists, they were being blamed for everyone's addiction.
The DEA cites 108 prosecutions of physicians during the past four years; 83 pleaded guilty or no contest, while 16 others were convicted by juries. Eight cases are pending, and one physician is being sought as a fugitive.
In congressional testimony, the agency's deputy assistant administrator, Joseph T. Rannazzisi, estimated that fewer than 1% of the nation's physicians — under 9,000 — illegally provide prescription drugs to patients. He told lawmakers it is far more common for people to illegally obtain prescription drugs from friends and family members.
"It is not merely illegal but could feed or lead to an addiction and place that loved one in a life-threatening situation," Rannazzisi said.
It is impossible to reliably measure painkiller abuse.
A 2004 government study estimated between 2 million and 3 million doses of codeine, hydrocodone and oxycodone are stolen annually from pharmacies, distributors and drug manufacturers. The AP's analysis only included retail sales and did not include estimates of diverted pharmaceuticals.
John Charles, director of medical affairs at the Grand Strand Regional Medical Center in Myrtle Beach, practices pain management. A few years ago, Charles said, he took a drastic step to reduce his potential legal risks: He stopped prescribing painkillers.
The decision gave him peace of mind, but he does not expect there to be less of a need for painkillers or physicians who prescribe them.
"People with cancer are surviving longer, elderly people are living longer," Charles said. "So, physicians are walking a fairly fine line. We're walking a narrow path. And I think we'll continue to see it for a while."

Pain medicine use has nearly doubled

By FRANK BASS, Associated Press WriterMon Aug 20, 10:33 PM ET
Retail sales of five leading painkillers nearly doubled from 1997 to 2005, reflecting a surge in use by patients nationwide who are living in a world of pain, according to a new Associated Press analysis of federal drug prescription data.
The analysis reveals that oxycodone usage is migrating out of Appalachia to areas such as Columbus, Ohio, and Fort Lauderdale, Fla., and significant numbers of codeine users are living in many suburban neighborhoods around the country.
The amount of five major painkillers sold at retail establishments rose 90 percent between 1997 and 2005, according to Drug Enforcement Administration figures.
More than 200,000 pounds of codeine, morphine, oxycodone, hydrocodone and meperidine were purchased at retail stores during 2005, the most recent year represented in the data. That is enough to give more than 300 milligrams of painkillers to every person in the country.
Oxycodone, the chemical used in OxyContin, is responsible for most of the increase. Oxycodone sales jumped nearly six-fold between 1997 and 2005. The drug gained notoriety as "hillbilly heroin," often bought and sold illegally in Appalachia. But its highest rates of sale now occur in places such as suburban St. Louis and Fort Lauderdale.
"What we're seeing now is the rest of the nation catching up to where we were," said Robert Walker, a researcher at the University of Kentucky Center on Drug and Alcohol Research.
The world of pain extends beyond big cities and involves more than oxycodone.
In Appalachia, retail sales of hydrocodone — sold mostly as Vicodin — are the highest in the nation. Nine of the 10 areas with the highest per-capita sales are in mostly rural parts of West Virginia, Kentucky or Tennessee.
Dr. Jeffrey Gordon, director of the blood and cancer center at Day Kimball Hospital in Putnam, Conn., said Vicodin is a popular painkiller to give patients after surgery, and many doctors are familiar with it.
"Over the past 10 years, there has been much better education in the medical community to ... ask if people are having pain and to better diagnose and treat it," Gordon said.
Suburbs are not immune to the explosion.
While retail sales of codeine have fallen by one-quarter since 1997, some of the highest rates of sales are in communities around Kansas City, Mo., Nashville, Tenn., and on New York's Long Island.
The DEA figures analyzed by the AP include nationwide sales and distribution of drugs by hospitals, retail pharmacies, doctors and teaching institutions. Federal investigators study the same data trying to identify illegal prescription patterns.
An AP investigation found these reasons for the increase:
_The population is getting older. As age increases, so does the need for pain medications. In 2000, there were 35 million people older than 65. By 2020, the Census Bureau estimates the number of elderly in the U.S. will reach 54 million.
_Drugmakers have embarked on unprecedented marketing campaigns. Spending on drug marketing has zoomed from $11 billion in 1997 to nearly $30 billion in 2005, congressional investigators found. Profit margins among the leading companies routinely have been three and four times higher than in other Fortune 500 industries.
_A major change in pain management philosophy is now in its third decade. Doctors who once advised patients that pain is part of the healing process began reversing course in the early 1980s; most now see pain management as an important ingredient in overcoming illness.
Retired Staff Sgt. James Fernandez, 54, of Fredericksburg, Va., survived two helicopter crashes and Gulf War Syndrome over 20 years in the Marine Corps. He remains disabled from his service-related injuries and takes the equivalent of nine painkillers containing oxycodone every day.
"It's made a difference," he said. "I still have bad days, but it's under control."
Such stories should hearten longtime advocates of wider painkiller use, such as Russell Portenoy, head of New York's Beth Israel pain management department. But they have not.
"I'm concerned and many people are concerned, that the pendulum is swinging too far back," he said.
Consider:
_More people are abusing prescription painkillers because the medications are more available. The vast majority of people with prescriptions use the drugs safely. But the number of emergency room visits from painkiller abuse has increased more than 160 percent since 1995, according to the government.
_Spooked by high-profile arrests and prosecutions by state and federal authorities, many pain-management specialists now say they offer guidance and support to patients but will not write prescriptions, even for the sickest people. The increase in painkiller retail sales continues to rise, but only barely. There was a 150 percent increase in volume in 2001. Four years later, the year-to-year increase was barely 2 percent.
_People who desperately need strong painkillers are forced to go long distances — often to a different state — to find doctors willing to prescribe high doses of medicine. Siobhan Reynolds, widow of a New Mexico patient who needed large amounts of painkillers for a connective tissue disorder, said she routinely drove her late husband to see an accommodating doctor in Oklahoma.
Perhaps no place illustrates the trends and consequences for the world of pain better than Myrtle Beach, S.C., a sprawling community of strip malls, hotels and bars perched along a 60-mile strip of sand on the Atlantic Ocean. The metro area is home to 350,000 people but sees more than 14 million tourists annually, drawn to its warm water, golf courses and shopping.
During the eight-year period reflected in government figures, oxycodone distribution increased 800 percent in the area of Myrtle Beach, partly due to a campaign by Purdue Pharmaceuticals of Stamford, Conn. The privately held company has pleaded guilty to lying to patients, physicians and federal regulators about the addictive nature of the drug.
Use of other drugs soared in the area, too: Hydrocodone use increased 217 percent; morphine distribution went up 180 percent; even meperidine, most commonly sold as Demerol, jumped 20 percent.
It is no small wonder that federal authorities suspected the area was home to a notorious "pill mill," or a clinic that dispenses prescription medication without verifying that it's needed.
The U.S. attorney for South Carolina secured a 58-count indictment in June 2002 against seven physicians and one employee of the Comprehensive Care and Pain Management Center, a nondescript storefront on Myrtle Beach's main drag.
Tipped off by local pharmacists concerned about an increase in the volume of painkiller prescriptions, the federal investigation created a furor in the medical profession. The owner, D. Michael Woodward, was sentenced to 15 years in the case and has relinquished his license.
A second physician, Deborah Bordeaux, had worked at the clinic less than two months before quitting in disgust. Bordeaux, now serving a two-year prison term, was threatened with a 100-year sentence if she did not help the prosecution.
Officials with the Justice Department and DEA would not discuss what some activists say is a "war on doctors."
Reynolds, the widow who drove her late husband hundreds of miles for his pills, became an activist after the Myrtle Beach indictments. She contributed money to appeal some of the criminal convictions in South Carolina and started the Pain Relief Network, an advocacy organization for people living in pain. She believes the doctors sent to prison were railroaded.
"It was a witch hunt," she said.
Bordeaux's husband, Edworth Swaim, agrees. A retired U.S. Postal Service employee, Swaim believes his wife was sentenced to two years because she would not turn on her former colleagues. Even though Bordeaux had worked at the clinic less than two months and eventually sued over what she alleged was rampant Medicare fraud, he said she did not stand a chance of avoiding prison.
"She wasn't guilty of anything, so she wasn't going to plead to anything," Swaim said. "She was absolutely railroaded, made an example of. I can't tell you how angry I am."
Myrtle Beach physicians are not convinced that the "Myrtle Beach Eight," as they became known, were innocent.
A Myrtle Beach internist who also works in addiction medicine, Brian Adler, said physicians were flooded with patients seeking pain medicine after the clinic was shut down.
The community has a slightly higher-than-average number of older people and relatively high numbers of people between 21 and 64 who describe themselves as disabled.
"There's a significant problem with narcotics in this area," Adler said. After the pain management clinic closed, "all those folks were like rats, scurrying from a burning building, trying to get their fix."
Other physicians were concerned about patients with legitimate needs for painkillers. The federal bust raised the stakes.
When radio commentator Rush Limbaugh settled a federal case charging him with illegally obtaining painkillers, he did not get prison time. Neither did NFL star Brett Favre, who publicly acknowledged an addiction to Vicodin that he obtained legally.
To pain management specialists, they were being blamed for everyone's addiction.
The DEA cites 108 prosecutions of physicians during the past four years; 83 pleaded guilty or no contest, while 16 others were convicted by juries. Eight cases are pending, and one physician is being sought as a fugitive.
In congressional testimony, the agency's deputy assistant administrator, Joseph T. Rannazzisi, estimated that fewer than 1 percent of the nation's physicians — under 9,000 — illegally provide prescription drugs to patients. He told lawmakers it is far more common for people to illegally obtain prescription drugs from friends and family members.
"It is not merely illegal but could feed or lead to an addiction and place that loved one in a life-threatening situation," Rannazzisi said.
It is impossible to reliably measure painkiller abuse.
A 2004 government study estimated between 2 million and 3 million doses of codeine, hydrocodone and oxycodone are stolen annually from pharmacies, distributors and drug manufacturers. The AP's analysis only included retail sales and did not include estimates of diverted pharmaceuticals.
John Charles, director of medical affairs at the Grand Strand Regional Medical Center in Myrtle Beach, practices pain management. A few years ago, Charles said, he took a drastic step to reduce his potential legal risks: He stopped prescribing painkillers.
The decision gave him peace of mind, but he does not expect there to be less of a need for painkillers or physicians who prescribe them.
"People with cancer are surviving longer, elderly people are living longer," Charles said. "So, physicians are walking a fairly fine line. We're walking a narrow path. And I think we'll continue to see it for a while."
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Associated Press writers Dave Collins in Hartford, Conn., and Samira Jafari in Pikeville, Ky., contributed to this story.
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On the Net:
Pain Relief Network, http://www.painreliefnetwork.org
Drug Enforcement Administration, http://www.usdoj.gov/dea
Drug Abuse Warning Network, http://dawninfo.samhsa.gov/
American Academy of Pain Management, http://www.aapainmanage.org/