Drug overdose deaths spike among middle-aged women

From USA Today:

More women are dying from prescription painkiller overdoses than ever before, highlighting what the Centers for Disease Control and Prevention calls a growing public health epidemic.

The CDC study shows that while men are still more likely to die of overdoses, the number of deaths among women increased five-fold in the last decade, four times more than deaths in women from cocaine and heroin combined, says CDC director Tom Frieden. About 12% of these deaths were suicides, CDC experts said.

The rate of prescription drug overdose deaths of women increased 400% from 1999 to 2010, compared with an increase of 250% for men. More men die of prescription painkiller overdoses — about 23,000 in 2010, compared with 15,300 for women.

Women may be more prone to overdoses because they're more likely to have chronic pain, be prescribed painkillers, have higher doses, and use them longer than men, said Linda Degutis, director of CDC's National Center for Injury Prevention and Control.

Overdose deaths from prescription painkillers skyrocketed over the past decade despite no major increases in the need for prescription painkillers over the last 20 years, said Chris Jones, a health scientist at CDC. Doctors are prescribing medications more frequently for patients who may not need them, a trend in the medical profession that needs to be reversed, Frieden said.

Women between 45 and 54 had the greatest increases in drug overdose deaths, likely because of dependence on prescription drugs to ease chronic pain, experts said.

Posted: 7/3/2013 1:45:00 PM

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Hope for chronic pain sufferers as new drug becomes available

From The Telegraph (UK):

Many people on opiate-based drugs for chronic pain suffer unpleasant side effects from them including constipation and vomiting.

A new drug called Palexia becomes available for doctors to prescribe today, which trials show could be tolerated by many more.

Pain management experts hope it will mean more patients sticking with their medication and getting the relief they need.

Palexia, the brand name of the drug tapentadol, works in two ways. First, it works as a traditional opioid, stopping pain signals getting through nerve junctions in the spinal cord called synapses, and reducing the perception of pain in the brain itself.

Secondly, it works to stop pain messages being transmitted by reducing levels of a neurotransmitter called noradrenaline.

It is the first such painkiller on the British market to work in both these ways.

Posted: 5/17/2011 8:32:00 AM

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Pain Management Failing as Fears of Prescription Drug Abuse Rise

From ScienceDaily:

Millions of Americans with significant or chronic pain associated with their medical problems are being under-treated as physicians increasingly fail to provide comprehensive pain treatment -- either due to inadequate training, personal biases or fear of prescription drug abuse.

A pharmaceutical expert in pain management in the College of Pharmacy at Oregon State University says the issue is reaching crisis proportions, and in two new professional publications argues that health consumers must be aware of the problem and in many cases become more informed, persistent advocates for the care they need and deserve.

Adequate pain treatment has always been a concern, said Kathryn Hahn, a pharmacist, affiliate faculty member at OSU and chair of the Oregon Pain Management Commission, in part because it's not a major part of most physician's medical training. Even though they will often see a stream of patients with pain problems throughout their careers, they may only get a few hours of education on the use of opioids in medical school.

In recent years, the problems have dramatically increased due to concerns about prescription drug abuse, in which drugs such as oxycodone are often stolen from homes or otherwise misused. In a 2006 survey of teenagers, 62 percent said prescription pain relievers were easy to get from their parents' medicine cabinet. One analysis concluded that admissions to federally supported treatment programs for prescription opioid abuse increased 342 percent from 1996 to 2006 -- a comprehensive problem that is also estimated to cost insurance companies tens of billions of dollars a year.

"Surveys show that at least 30 percent of patients with moderate chronic pain and more than 50 percent of those with severe chronic pain fail to achieve adequate pain relief," she wrote in one article. "The economic impact of acute and chronic pain exceeds $100 billion per year in the U.S. alone."

Community pharmacists, she said, are often on the front lines of this issue and constantly see individuals with pain concerns and inadequate pain management by their health care providers. They can often help serve as advocates, improve lines of communication between patients and their doctors, and help patients manage their prescribed drug therapies.

Health insurers also have an important role to play in reducing prescription drug abuse, Hahn said. They can help educate physicians on appropriate use, advocate for universal precautions in use of pain medicines, restrict off-label uses of readily diverted opioids, pay for multidisciplinary pain management programs, and take other steps.

Posted: 1/6/2010 9:11:00 AM

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Probing the nuances of pain management

From CAP Today:

People who develop chronic physical pain often require a combination of the art and science of medicine to reclaim or maintain a normal life. And the clinical laboratory is increasingly weighing in on the scientific side of the pain management equation with testing that can improve the safety and efficacy of opioid and other pain medications.

The lab’s role in pain management includes verifying that patients are taking their prescribed medications as directed and providing therapeutic drug monitoring (drug concentrations) to help determine if the medication is doing what it’s intended to do—“give people relief from pain,” says Paul Jannetto, PhD, assistant professor of pathology and director of clinical chemistry toxicology at the Medical College of Wisconsin in Milwaukee.

The No. 1 reason urine opiate drug screening is done by pain management physicians is to monitor patients for compliance, said Dr. Jannetto in a presentation at the 2008 American Association for Clinical Chemistry meeting. But some clinicians are also using therapeutic drug monitoring and pharmacogenomic testing as part of pain management, especially in difficult cases.

While statistics show that pain testing is underused, says Robert Middleberg, PhD, laboratory director at NMS Laboratories in Willow Grove, Pa., and a consultant to the CAP Toxicology Resource Committee, more and more physicians are interested in it. That’s evident, he adds, by the growing number of pain management labs “sprouting up.” In addition, “insurers are covering the testing at profitable rates for laboratories,” he says, which tells you they see an actuarial benefit to anteing up.

Yet pain management testing is no slam-dunk in terms of always providing easy yes or no answers, even in the realm of urine drug screening, which many physicians require patients who take opioids to undergo continually, Dr. Jannetto said.

On the upside, urine drug screening, which provides a two- to three-day detection window for most opiates, is “fast, automated, inexpensive, and noninvasive” for monitoring patients, he noted. But “screening” is the operative word. The screening tests are typically competitive immunoassays based on competition between drug in the patient’s sample and labeled drug for the antibodies’ binding sites. The antibodies are directed against drug groups or classes—opiates, for example. Thus, they can’t be used to identify or quantitate the concentration of a specific opiate such as morphine, codeine, or heroin. A more specific alternative chemical method (GC/MS) must be used to obtain a confirmed analytical result.

A patient taking prescribed hydrocodone who tests positive on the urine opiate screening assay could have sold that medication and used heroin, morphine, codeine, or even oxycodone, all of which can turn the screening test positive, Dr. Jannetto cautions.

He advises physicians to order confirmatory testing to pinpoint what the patient is really taking in cases, for example, where the person displays erratic behavior in the office or is suspected of diverting the medication.

Confirmatory testing uses mass spectrometry, which, as NMS’ Dr. Middleberg explains, provides “a molecular fingerprint of a compound based on structural characteristics of the substance.” The testing identifies not only the parent drug but also its metabolites, which can be tricky for physicians to interpret without guidance from the laboratory.

Physicians sometimes also receive unexpected negative results from urine drug screens for patients who are supposed to be taking an opioid or other medication. To prevent false-negatives, Dr. Jannetto said, clinicians and labs have to understand what the assays they are using will detect. Interpretation of results must also take into account that urine concentrations can vary extensively with fluid intake and other biological variables. In addition, they should realize that cross-reactivity varies among test manufacturers’ kits.

Oxycodone urine screening assays...cause confusion for the physicians, Dr. Jannetto said, because the lab’s urine opiate screening assay may not cross-react with oxycodone at all or very well. “So doctors will say, ‘My patient is on oxycodone and sometimes tests positive and sometimes not on your assay—what’s going on?’ The answer is that whether the person tests positive may have to do with his or her hydration state and the level of oxyco­done in the urine. The lab actually has a separate oxycodone screen with a lower cutoff that specifically detects oxycodone and its metabolite [oxymorphone],” he said.

Of course, says Gwen McMillin, PhD, the most common reason a drug screen comes back negative is that the patient is not taking the drug or taking it less frequently than prescribed. But “perhaps the patient didn’t realize he had to produce a urine sample until he got to the office, and then drank a lot of fluids to produce the sample,” says Dr. McMillin, assistant professor in the University of Utah Department of Pathology and medical director of toxicology at ARUP Laboratories. “Or the patient could have accelerated metabolism or drug elim­ination, or have an enzyme inducer that’s ramped up his metabolism. In rare cases, a person with Celiac disease or Crohn’s disease might not absorb a medication.”

Some pain patients adulterate their urine samples so they’ll test negative for illicit drugs. Dr. Jannetto sees such samples about five percent of the time in his laboratory. The patient can drink a lot of water to dilute the urine, which drops the drug below the cutoff on a screening assay. The alternative is to add products to the urine that contain acid, nitrites, and various other compounds that interfere with the immunoassays, he said. Third, patients can buy drug-free urine on the Internet.

Pain management physicians typically do not do witnessed urine collections, Dr. Jannetto noted. But simple countermeasures can help flag potentially adulterated samples. You can test the urine-specific gravity to identify very dilute urine, and look at the pH to make sure the patient hasn’t added acid to the sample. “If the pH is less than 3, that’s suspicious.”

Dr. Jannetto routinely advises physicians doing pain management testing to run creatinine on urine samples, which is very cost-effective.

“If the creatinine is less than 20 mg/dL, that person is well hydrated,” which the physician might consider when interpreting negative results, he advised. Some samples his labor­atory receives “have no creatinine [<5 mg/dL], urea, no nothing ...” And that, of course, isn’t human urine.

Urine screening is most vulnerable to sample tampering that affects results. But some forms of adulteration, Dr. Middleberg says, can also affect mass spectrometry results, even when the lab is using state-of-the-art technology. That’s one reason labs do adulteration testing in the form of pH, nitrites, oxidants, and creatinine, he says. Nitrites, which are in products used to adulterate urine testing, “tend to have a particular effect on the ability to measure can­nabinoids in urine by mass spectrometry,” he says, “especially depending on the pH of the urine.”

Urine drug monitoring using mass spectrometry won’t detect patients taking a higher dose of a drug than prescribed, Dr. Middleberg says. The clinician could “attempt to get at that with blood or serum testing, but even there you have to consider [pharmacogenomics] and other pharmacokinetic differences, so it’s never easy.”

While not widely used, therapeutic drug monitoring on blood samples can help physicians manage more complex cases. “Great candidates” for TDM, says Loralie Langman, PhD, associate professor at Mayo College of Medicine and director of the toxicology and drug monitoring laboratory at Mayo Clinic in Rochester, Minn., are patients who are “atypical”—that is, requiring higher or lower doses of a drug or experiencing significant adverse drug reactions.

Physicians who use TDM to troubleshoot, however, will be somewhat in the dark without the patient’s baseline because “what’s toxic in one person may be therapeutic in another,” she notes. Yet that can change for an individual patient as the person develops tolerance to the opioid. “Performing TDM is not a bad idea” when dealing with a drug that doesn’t have a well-established therapeutic range or is known to have a large interpatient variability, especially when compliance is an issue, Dr. Langman says.

As for pharmacogenomic testing, Dr. Jannetto says physicians rarely test for CYP2D6, an enzyme responsible for metabolizing 20 to 25 percent of prescription medication and over-the-counter products. “And in the case of opioids/opiates—oxycodone, hydrocodone, and codeine —it’s an important player.”

A poor metabolizer of CYP2D6, which two to 10 percent of most ethnic groups are, says Dr. Jannetto, will build up higher concentrations of the parent drugs oxycodone or hydro­codone, and may end up with more side effects. “In the case of co­deine, poor metabolizers of CYP2D6 won’t get any pain relief because the analgesic properties of codeine come from its CYP2D6 metabolite morphine.”

As an alternative to doing CYP2D6 genotype testing, the clinician can also identify poor metabolizers by doing TDM. But even if clinicians identify a poor metabolizer, says Dr. Jannetto, there are no formal guidelines for how to adjust the person’s pain medication dosages. Thus, “option B,” he adds, may be to start the person on a low dose of an opioid and titrate it up until the person gets pain relief. Or the clinician could put the person on a medication metabolized by a different enzyme. “Fentanyl is one option, as it’s metabolized by 3A4 and 3A5. Methadone is metabolized by multiple pathways, so that’s another option.”

Other medications a patient is taking can also inhibit CYP2D6, causing the patient to function as a poor metabolizer. For that and other reasons, pain management physicians or those prescribing pain medications should always ask the patient for a complete list of the medications he or she is taking, including over-the-counter medications and herbals, Dr. Jannetto says.

TDM and PGx testing combined not only optimize pain management in some cases but also increase safety for patients and for clinicians medico­legally when prescribing opioids.

The bottom line in pain management, she says, is to treat pain safely and adequately so patients no longer have to do what some in her care have described: “expend a huge amount of energy trying to isolate the pain into a corner of their day or life ... like a lion-tamer having to keep the lion at a distance.”

Posted: 4/30/2009 10:55:00 AM

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