Facing the Prescription Drug Abuse Epidemic

EDs see big increase in overdoses, putting strain on clinical labs

By Gary Tufel

In recent years, the growing number of Americans addicted to prescription pain medications has become staggering. And when obtaining such highly addictive drugs becomes difficult, addicts are turning to heroin in massive numbers because it’s a cheap and often readily available substitute. The result of these trends is an enormous and rapidly growing health problem, as well as a huge law enforcement challenge.

During 2012, heroin deaths increased sharply in many states, according to a study of death certificate data from 28 states published by the Centers for Disease Control and Prevention.¹ Despite these findings, still more than twice as many people died from prescription opioid overdoses as died from heroin in these states in 2012. (For more information, see “Study Findings.”)

Though not directly addressed by the CDC study, two things appear to be driving the increase in heroin overdoses: widespread prescription opioid exposure and increasing rates of opioid addiction; and an increased heroin supply. While the majority of prescription opioid users do not become heroin users, previous research found that approximately 3 out of 4 new heroin users report having abused prescription opioids prior to using heroin. This relationship between prescription opioid abuse and heroin is not surprising; heroin is an opioid, and both drugs act on the same receptors in the brain to produce similar effects. Heroin often costs less than prescription opioids and is increasingly available.

The most recent studies published by CDC confirm these grim statistics. In 2014, more people in the United States died from drug overdoses than during any previous year on record. Opioids—primarily prescription pain relievers and heroin—were the main drugs associated with such deaths, and were involved in 28,647 overdose deaths, or 61% of all overdose deaths in 2014.²

“Reducing inappropriate opioid prescribing remains a crucial public health strategy to address both prescription opioid and heroin overdoses,” says CDC Director Tom Frieden, MD, MPH. “Addressing prescription opioid abuse by changing prescribing is likely to prevent heroin use in the long term.”¹

MONITORING PRESCRIPTION DRUG USE

Across the country, labs are doing their part to detect and reduce the abuse of prescription opioid painkillers and the consequent rise in associated fatalities. It’s a big battle, because pain—now the fifth vital sign—has become top-of-mind for patients and healthcare providers. Hospital labs, reference labs, specialized pain management labs, and clinical labs are all addressing the issue, says Marilyn Huestis, PhD, chief of chemistry and drug metabolism at the intramural research program of the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.

“Primary care doctors need to be thinking more about potential substance abuse and prescreening practices,” says Huestis. “Labs should be talking with physicians about the best ways to monitor people’s drug use to improve identification of those who need treatment. Pain management labs have a responsibility to monitor their patients for signs of abuse. It shouldn’t begin with forensic labs reporting overdoses.”

Adequate testing to monitor a patient’s drug use is usually difficult for doctors because they see most patients only once every few months. In pain management, the patient may be asked to sign a behavioral contract agreeing to be tested for prescription and illicit drugs—for the drugs the patient has been prescribed to take, and those for which they don’t have a prescription.

“A positive test can reveal that a patient has been doctor-shopping; that is, going from doctor to doctor to obtain the painkiller they want,” says Huestis. “If a patient refuses to agree to periodic testing, the doctor can refuse to prescribe the drug.”

Huestis notes that new legislation will require that federally mandated workplace drug testing include urine testing for additional synthetic opioids. And new guidelines are in place for oral fluid testing that will include tests for such synthetic opioids as hydrocodone and oxycodone. Immunoassays exist for many such synthetic opioids, and more are being developed. (For more information, see “New Testing Standards on the Way.”)

In October 2015, FDA granted premarket notification (510(k)) clearance to the DRI Hydrocodone assay by Thermo Scientific, Fremont, Calif, a homogeneous enzyme immunoassay that specifically detects hydrocodone and is said to offer excellent cross-reactivity to the major metabolites hydromorphone and hydromorphone-glucuronide. The assay utilizes liquid, ready-to-use reagents, which can be run in both qualitative and semiquantitative modes. Calibrators and controls are sold separately.

According to the company, the DRI Hydrocodone assay has the requisite sensitivities to meet the newly proposed 300 ng/mL detection cut-off guidelines proposed by the Substance Abuse and Mental Health Administration (SAMHSA), which oversees the testing of federally regulated employees. Many other organizations also follow SAMHSA guidelines.

“Hydrocodone is a semisynthetic opiate that is widely prescribed in the United States to treat moderate to severe pain,” says Kevin J. Barta, senior manager for clinical diagnostics and niche products management at Thermo Fisher Scientific. “However, the potential for illicit use of prescription opiates is high, making hydrocodone also very popular as an abused substance. Pain management physicians are therefore faced with a challenge when treating patients: to determine whether their prescription is actually needed, and whether it will be used by the patient as intended.”

Barta suggests that there is a need to differentiate assays used for therapeutic drug monitoring from those used to test for the presence of drugs of abuse in a sample. “Therapeutic drug monitoring assays provide valuable information for the physician, to determine the effective dosage for an individual patient,” he notes. “In contrast, drugs-of-abuse assays can inform the physician about both prescription medications and illicit substances the patient may be using.”

According to Thermo Fisher, the new DRI Hydrocodone assay demonstrates good correlation with liquid chromatography–tandem mass spectrometry (LC-MS/MS) and has excellent assay precision. It has excellent specificity and sensitivity, making it an easy-to-use screening tool for hydrocodone in urine samples, with applications for a variety of clinical chemistry analyzers.

But in the long run, says Huestis, it won’t be enough to use only immunoassays to detect synthetic opioids, because there aren’t enough tests in that format to cover all the prescription drugs of interest, or their cutoffs are too high. Huestis believes that it will take testing via LC-MS to adequately screen for and confirm patient abuse of pain prescription drugs, and she points out that many labs are already utilizing LC-MS testing for initial screening, because they can test with high sensitivity and specificity for many analytes at one time.

But a big factor is that as the government clamps down on prescription drug abuse, many addicted users turn to heroin, which has a different potency, is cheaper and easier to obtain, and works with the same receptors in the body to produce the desired high. And heroin can be smoked as well as injected; it goes right to the brain and offers a nearly instantaneous high.

“It’s not generally understood how addictive opioids are. There’s a very high abuse factor,” says Huestis. “Poverty and other difficulties often breed opioid use. The United States uses 98% to 99% of the world’s hydrocodone, and often the entry point for young people is raiding their parents’ drug cabinet for painkillers. They’re looking to forget their problems and don’t realize how addictive these drugs are. Many transfer to heroin use when prescription opioids are unavailable or too expensive.”³

Huestis says that every federal agency is trying to address the problem of opioid abuse—including NIDA, which recently helped support the development of a nasal spray designed to rapidly reverse opioid overdose. In 2013, NIDA entered into a partnership with Lightlake Therapeutics Inc, New York City, a biopharmaceutical company developing novel treatments for addiction, to apply new technology toward developing a lifesaving intervention for opioid overdose. The resulting technology, an intranasal formulation of naloxone, has recently received FDA approval, and will be marketed under the brand name Narcan by Lightlake partner Adapt Pharma Ltd, Dublin, Ireland. Anyone can quickly administer the nasal spray, Huestis says, and then call 911 for additional help.⁴

“Pain management is a huge industry, and there are many pain management labs,” says Huestis. “But the government is running behind in determining appropriate charges for the LC-MS testing that is needed. LC-MS testing can simultaneously conduct many assays, but it’s much more expensive than immunoassays. The government is assessing how to fairly reimburse for these new tests, and how to reduce overcharging by some laboratories.”

BIG CHALLENGE FOR LABS

This is a big challenge for the clinical lab, says Kelli Mogush, senior marketing manager at Siemens Healthcare Diagnostics, responsible for Siemens’ Syva line of drug testing products.

“Because of prescription drug abuse, the Drug Enforcement Administration (DEA) is cracking down on prescribed medications. Now people can’t get their pain meds—and remember these are very addictive opioids. So someone who can’t get their Vicodin, for example, ends up turning to street drugs, and either buying Vicodin on the street (at the going rate of $10 per pill), or worse, turning to heroin.

“Because of all this, heroin is now a growing problem again worldwide,” says Mogush. “The heroin that is available now is very pure. It can be inhaled instead of being injected, and it is very cheap. This process is creating a new profile for the typical heroin addict. It could be anyone.”

Clinical laboratories often see the end result of this process, when newly minted addicts end up in the emergency department of the local hospital. “This is a whole new type of user—people who are not usually familiar with drug abuse,” says Mogush. “Consequently, they overdose on their pain meds; they buy stuff on the street that may or may not be what they think it is; or they overdose on heroin.”

Those who don’t die encounter other difficulties. “There are health issues that arise from heroin use or long-term prescription opioid use,” says Mogush. “Vicodin and Percocet have Tylenol in them, and Tylenol use is one of the leading causes of liver transplants. And there are other issues, not to mention AIDS-related issues.

“Eventually, even those who begin by inhaling or snorting heroin will have to start injecting once their tolerance reaches a certain point. This is why SAMHSA is going to implement guidelines for pain management clinics,” says Mogush. “These are clinics designed to treat people for chronic pain, and they occupy a borderline between clinical and forensic functions. While they are clinics with pain management doctors, they also perform testing to make sure their patients are not diverting their drugs. Someone could sell their Vicodin on the street for the going rate, for instance, and make enough money to buy a lot more heroin.”

Such testing has been one of the drivers of Siemens’ success with its Syva instrument and reagent sales. “We have seen sales of our opiate tests skyrocket,” says Mogush. “And the same holds true for our clinical chemistry colleagues who use Syva reagents on their Advia, Beckman Coulter, or Dimension systems—all of which are in clinical labs.”

WHY PRESCRIPTION DRUG ABUSE HAS SKYROCKETED

The abuse of prescription drugs has changed American culture like no drug abuse before ever has, says Bob Stutman, who served as a special agent with DEA for 25 years and is now principal of the Stutman Group, Boca Raton, Fla, a substance abuse consultancy. “It’s been more of a change than even the LSD days of 1967–1978, or the crack cocaine culture that began in the mid-1980s,” he says. (For more information, see “How Abuse of Prescription Drugs Has Changed American Culture.”)

During his last 6 years with DEA, Stutman headed the administration’s New York office, the DEA’s largest. He points to several historical factors that have contributed to the enormous increase in prescription drug use and abuse:

• In 1993, drug manufacturers began advertising prescription drugs heavily, a practice allowed only in the United States and New Zealand.
• The rise in Oxycontin use due to fraudulent marketing by the manufacturer that ignored the drug’s addictive potential.
• In 1995, American medical schools introduced pain as a fifth vital sign, opening the door to large-scale prescribing of pain medications based mostly on subjective factors.
• Many physicians receive bonuses based not on patient outcomes, but on whether patients like them.

THE ROLE OF THE CLINICAL LAB

Stutman decries the use of the term “heroin epidemic.” “People usually use heroin—which is similar to Oxycontin, Percocet, and Vicodin—when they can’t get their prescription drugs. Heroin is also 70% cheaper than prescription drugs, and about 90% of heroin addicts start with prescription drugs,” he says. “My problem is that these drugs are killing about 48,000 people a year in the United States.”

A major challenge is making sure that patients take the medications they’ve been prescribed and that the medications don’t go to a third party, Stutman says. The clinical lab has a major role to play in this.

“Before a patient starts prescription drug therapy it is recommended to check if drug abuse could be an issue,” says Randy Pritchard, life cycle leader for core reagents with Roche centralized and point-of-care solutions, Rotkreuz, Switzerland. “Many state medical boards and healthcare regulatory agencies have already adopted drug testing before and within therapy as part of their pain management guidelines.

“Therapeutic drug monitoring to set an individual dose for prescription drugs would not provide much benefit, while increasing treatment costs,” says Pritchard. “However, the identification of abuse and compliance monitoring testing have become an important part of therapy to ensure a safe and efficient pain treatment with prescription drugs.”

Additionally, despite appropriate education, some patients—especially among the elderly—become confused by their dosage plan and take more than one dose at the same time. A drug test with the ability to provide a rough quantification can determine overdose.

“Doctors don’t want to be cops, but they should have every patient who is prescribed opioids or benzodiazepines sign a consent form to be tested for prescription drugs on a random basis,” says Stutman. “It’s voluntary; but if a patient refuses, the doctor can refuse to rewrite their prescription.”

“Prescription drug monitoring in the clinical lab is much more effective than forensic testing,” Stutman adds. Such monitoring tests for many more drugs, and for lower levels of such drugs. “It’s the only way doctors should go,” he says.

Drugs-of-abuse tests by Roche provide the ability to use high and low concentration cut-offs and a rough quantification mode of the drug concentration in a patient sample, notes Pritchard. “These test features allow the laboratory to identify acute intoxication indicated by high concentrations, as well as abuse that has taken place a few hours or days before the test, as indicated by low concentrations. In this context, drug abuse tests are used to identify the consumption of the drug.

“In combination with other information about current prescriptions, and the individual’s behavior, the physician has the information needed to diagnose addiction and, together with the patient, initiate further treatment,” says Pritchard.

Stutman notes that doctors can be open to criminal prosecution and civil liability for not making good faith efforts to prevent diversion by monitoring their patients’ prescription drug use. Doctors should also check state databases for evidence of patient drug abuse. “That protects the doctor, the patient, and the community—and clinical labs are a huge part of that effort.”

Gary Tufel is a contributing writer for CLP. For further information, contact CLP chief editor Steve Halasey via [email protected].

REFERENCES

1. Increases in heroin overdose deaths: 28 states, 2010 to 2012. Morbidity and Mortality Weekly Report. Atlanta: Centers for Disease Control and Prevention, October 3, 2014. Available at: www.cdc.gov/media/releases/2014/p1002-heroin-overdose.html. Accessed January 13, 2016.
2. Rudd RA, Aleshire N, Zibbell JE, Gladden RM. Increases in drug and opioid overdose deaths; United States, 2000-2014. Morbidity and Mortality Weekly Report. Atlanta: Centers for Disease Control and Prevention, January 1, 2016. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/mm6450a3.htm?s_cid=mm6450a3_w. Accessed January 13, 2016.
3. Parker M, Gleason S. Opioid dependency peaks among younger age group. MSU Today. East Lansing, Mich: Michigan State University, December 22, 2015. Available at: http://msutoday.msu.edu/news/2015/opioid-dependency-peaks-among-younger-age-group/?utm_source=weekly-newsletter&utm_medium=email&utm_campaign=standard-promo&utm_content=text. Accessed January 13, 2016.
4. FDA approves naloxone nasal spray to reverse opioid overdose [press release]. Rockville, Md: National Institute on Drug Abuse, November 18, 2015. Available at: www.drugabuse.gov/news-events/news-releases/2015/11/fda-approves-naloxone-nasal-spray-to-reverse-opioid-overdose. Accessed December 22, 2015.