FDA urges tighter controls for prescribed opioid painkillers

It's a common scenario.

A barely-used bottle of Vicodin, prescribed for your teenage son when his wisdom teeth were extracted, sits in your medicine cabinet for months - until your son's friend finds and steals it.

Abuse and diversion of opioid painkillers have become a public health crisis, experts agree. The number of overdose deaths has risen relentlessly from 4,000 in 1999 to nearly 17,000 in 2010 - more than 100,000 people in a decade, federal figures show.

That's why, after anguished debate, the U.S. Food and Drug Administration last month recommended making it harder for people to get refills of products like Vicodin. These products combine the opioid hydrocodone with over-the-counter analgesics such as acetaminophen or ibuprofen.

The change, which the Drug Enforcement Administration advocated, is expected to take effect next year. "The reason we approve these drugs is for people in pain," said Janet Woodcock, director of the FDA's center for drug evaluation and research. "But we can't ignore the epidemic on the other side."

Yet the tighter controls are just one step toward curbing that epidemic. Experts say that changing problematic medical and marketing practices - and deterring diversion of unused pills in medicine cabinets - will take more work.

"There are lots of reasons we got to where we are," said Michael Ashburn, a pain and palliative care specialist at the University of Pennsylvania. "There was a perception 15 years ago that a lot of people were needlessly suffering pain. But we didn't know the risks and benefits of using opioids to treat chronic non-cancer pain. The more we study it, the more we realize the limits."

Long before Dorothy fell asleep in a field of opium poppies on the way to Oz, the plant was known for its ability to induce sedation, pain relief, and euphoria.

Morphine, derived from poppies, is still the gold standard of pain medicine. The potency of synthetic "opioids" such as hydrocodone is measured in "morphine equivalent" doses.

These drugs act on receptors in the brain and body, triggering relaxation and a sense of pleasure, while suppressing pain perception - and breathing. With daily opioid use, physical dependence and tolerance can develop in mere days or weeks, studies show.

The DEA classifies drugs and their prescribing rules into categories, or "schedules," based on their potential for abuse.

Products with the opioid oxycodone, such as OxyContin and Percocet, are schedule II. Patients can get only a 90-day supply before seeing a doctor for another prescription, and the doctor cannot call or fax it in. A written script must be given to the pharmacy, which is under strict product storage and record-keeping requirements.

In the 1970s, drug companies successfully lobbied to have products that combine hydrocodone with over-the-counter pain-relievers classified as less-restrictive schedule III. Patients can get as many as five called-in refills of schedule III drugs over six months.

The companies argued - with little scientific evidence - that combination products were more effective and less prone to abuse than hydrocodone alone.

Since then, combination products have proliferated - the FDA says 93 are now on the market - and sales have soared. In 2011, 131 million prescriptions for combo hydrocodone products were filled by 47 million patients, compared with 35 million scripts for oxycodone-containing products filled by 15 million patients, according to IMS Health, a health information company.

This boom was bolstered by changes in the prevailing wisdom about treating pain.

"When I was in medical school in the 1990s, these drugs were reserved for cancer patients in the hospital," said Jeanmarie Perrone, an emergency medicine physician and opioid researcher at the University of Pennsylvania. "But there was a huge push to treat pain of all kinds more aggressively. Drug companies told doctors that if the pain was bad, you couldn't get addicted.

"Gradually," she said, "there has been a push to prescribe opioids for all pain indications," from terminal cancer to sprained ankles.

Many pain specialists now say the effectiveness of opioids has been oversold, while dangers such as respiratory arrest have been downplayed.

"There are lots of side effects, and these drugs are not the incredibly potent agents we think they are," said Eugene Viscusi, director of the pain management center at Thomas Jefferson University. "A whole variety of pain tends not to respond well to opioids."

Those types, he said, include headaches (especially migraines), muscle spasms, uterine cramping, pancreatitis, and nerve-related pain such as diabetic neuropathy and genital herpes ulcers.

"You see a lot of senseless dose escalation with modest benefit," he said.

Patients with chronic pain typically require escalating doses because they build a tolerance. Between 4 and 26 percent of patients on chronic opioid therapy become addicted, studies estimate.

Chronic pain can also be a mysterious mix of inflammation, misfiring nerves, scarring, and physical deterioration, all intensified by depression. "It becomes challenging to know how to treat it," Perrone said.

As the pendulum swings back toward more judicious use of opioids, some trends may help, experts say.

Recent guidelines for treating chronic pain agree that clinicians should assess patients' propensity for drug abuse, have them sign treatment agreements, conduct regular urine drug tests, and set upper dosing limits. Although pain specialists have routinely used such safeguards, primary care doctors are now embracing them.

"The standards of care are changing," and upper doses once considered safe are now recognized as too risky, said Teryl K. Nuckols, a UCLA physician who has evaluated the guidelines.

About 36 states have also developed prescription monitoring programs that doctors can check before writing orders for addictive painkillers. A Pennsylvania bill that would allow doctors to access a pharmacy database passed in the state House and is now before a Senate committee.

Consumers, meanwhile, can help curb abuse by disposing of, rather than stockpiling, leftover painkillers.

"We need to have an easy, proper way for patients and their families to return unused drugs for destruction," Ashburn said. "Surveys show that our children are as often reaching into our medicine cabinets as smoking marijuana" when they want to experiment with drugs.

Myth: prescribing opioids for chronic pain is backed by strong evidence.

Fact: Evidence of long-term efficacy is limited. Opioids are effective for short-term but not for long periods.

Myth: Physical dependence occurs only with high doses over long periods.

Fact: With daily use, opioid dependence and tolerance can develop in days or weeks.

Myth: Addiction is rare in patients prescribed opioids.

Fact: Estimates vary. From 4 to 26 percent of patients have an opioid use disorder. Among others, more than one in ten misuse opioids by: intentional over-sedation; adding alcohol; hoarding pills, raising dose on their own; and obtaining opioids from friends.

Myth: Addiction is the main risk of opioids.

Fact: Opioids' risks include respiratory depression and unintentional overdose, serious fractures from falls, hypogonadism, and other endocrine effects that can cause: increased pain sensitivity, chronic constipation, serious fecal impaction, and chronic dry mouth which can lead to tooth decay.

Source: Physicians for Responsible Opioid PrescribingEndText

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