COVER STORY

PAINKILLERS AND PILL POPPING

Profession mounts counteroffensive against the growing problem of opioid abuse

Among the remedies which it has pleased Almighty God to give man to relieve his suffering, none is so universal and so efficacious as opium.

Thomas Sydenham (1624-1689)

Opium's long and bizarre history dates back to ancient times, when it was used to induce euphoria, banish pain, and stimulate creativity. By the 1870s, this glamorized narcotic was an ingredient in many popular medicines touted as cures for every ill. These days, our fascination with opium and its derivatives continues.

Reports from Hollywood abound with celebrities seeking treatment for painkiller abuse—Matthew Perry and Melanie Griffith both recently checked into rehab after publicly acknowledging their addiction to prescription painkillers. The folks in Washington, D.C., are not immune, with Newsweek reporting on Arizona Sen. John McCain's wife, Cindy, and her battle with addiction to painkillers.

And unless you've been hiding your head in the sand, you are aware how aggressive the media have been in the coverage of the recent increase in narcotic abuse, particularly of OxyContin (oxycodone HCl controlled­ release, Purdue Pharma). The spotlight on OxyContin has intensified as the Drug Enforcement Administration recently announced a national strategy to contend with the painkiller's growing illegitimate use.

Climbing on board is the National Community Pharmacists Association, which, together with the National Institute on Drug Abuse (NIDA) and others, had heralded a new public initiative, Prescription Drugs: Misuse, Abuse, and Addiction.

"Our members are on the front lines in the war against drug abuse," said NCPA executive v.p. Calvin Anthony in a prepared statement. "We know the power of prescription medications to heal and improve life. We also know that, if abused or misused, those same medications can be agents of destruction."

Many community pharmacists have a long history as drug abuse educators, but all this media attention has raised many concerns. It has gotten so bad that one major supermarket pharmacy chain in Maine decided it would no longer stock OxyContin on its shelves. But is this in the patients' best interest?

Does all this media attention perpetuate the paranoia already felt by pharmacists and physicians when it comes to dispensing and prescribing opioids? Pharmacists are a critical link in the chain of drug distribution to the patient. If the practicing R.Ph. does not have adequate knowledge on pain management, that chain may break, leaving patients with valid Rxs unable to obtain their pain medications. It's important to distinguish between appropriate pain management and abuse. It is hoped the information that follows will allay the fears, misconceptions, and concerns associated with opioid use and address what's being done to curb the abuse.

Opiophobia

Pain is the single most common reason patients seek medical care, yet studies show it is widely undertreated in this country. It is estimated that more than 50 million Americans suffer from chronic pain. Arthur Lipman, Pharm.D., believes "the adverse outcomes of undertreated pain are more serious, more profound than the adverse outcomes of most of the medications used to treat pain." He is the director of clinical pharmacology, Pain Management Center, University of Utah Health Center, Salt Lake City.

Chronic pain is now considered to be a public health problem of major proportions, with one study reporting that more than 40% to 50% of patients in routine practice settings fail to receive adequate relief. Unremitting pain is associated with anxiety, depression, loss of independence, and interference with work and relationships. The annual cost of chronic pain, including medical expenses, lost income, and lost productivity, is an estimated $100 billion.

Many healthcare providers underprescribe painkillers because they overestimate the potential for patients to become addicted to opioids. This largely unfounded fear of prescribing opioid pain medications is known as opiophobia. Other factors that may interfere with effective pain management include fear of legal consequences, low priority of proper pain management in our healthcare system, and lack of current knowledge regarding pain management. Table 1 lists some reasons for the underutilization of opioids.

Table 1
REASONS FOR OPIOID UNDERUTILIZATION

In what was said to be the first case of its kind, a California jury recently found a physician liable for reckless neglect in undertreating pain in a terminally ill patient. "It should send a wake-up call to all providers that failing to adequately treat pain can result in accountability and substantial risk," said Kathryn Tucker, director of legal affairs for Compassion in Dying, a nonprofit patient advocacy group, which helped the family bring the case.

"The great majority of professional schools of medicine, nursing, and pharmacy do not spend adequate time (if any) on training practitioners to treat acute and/or chronic pain," noted Jeffrey Fudin, Pharm.D., DAAPM, clinical pharmacist at the Stratton VA Medical Center in Albany. And this is not just indicative of past years but still applies today. "The pharmacy students I've worked with are not sure of the role of opioids in any kind of pain," commented Scott Strassels, Pharm.D., BCPS, of the University of Washington department of pharmacy.

Dependence vs. addiction

Concerns about tolerance, physical dependence, and addiction have contributed to the reluctance among physicians, nurses, and pharmacists to utilize opioid analgesics in pain management.

"Physical dependence is often associated with addiction, but it's not the same thing as addiction," said Sidney Schnoll, M.D., Ph.D. He is an addiction specialist at the Medical College of Virginia, Richmond.

Physical dependence is described as the occurrence of withdrawal symptoms following abrupt discontinuation of narcotics. Dependence is nearly universal among patients receiving continual opioid therapy for a week or more. Schnoll called attention to the fact that physical dependence is not unique to opioids, but we use different terminology to define it. As an example, he cited the abrupt discontinuation of an antihypertensive medication. When adverse outcomes result from this disruption in therapy, it is called a "rebound effect," but, according to Schnoll, it is really the same as withdrawal.

Schnoll emphasized that addiction should be recognized as a disease. "There is now some evidence that about 8% to 10% of the population actually have some genetic underpinning that causes [addiction]," he continued.

The American Academy of Pain Management (AAPM), American Pain Society (APS), and American Society of Addiction Medicine (ASAM) adopted the latest definition for addiction this year. It is considered "a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its developments and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving."

Studies have consistently shown that iatrogenic addiction from opioid analgesia in patients experiencing pain is extremely rare. One study, published in the Journal of the American Medical Association, concluded that the trend of increasing the medical use of opioid analgesics to treat pain does not appear to contribute to increases in the health consequences of opioid analgesic abuse.

Tolerance is defined by the need for increasing doses of the medication to maintain analgesic effects. Tolerance can develop to both the analgesic effects of opioids and the unwanted side effects, such as respiratory depression, sedation, and nausea. "Much of what we learned in pharmacy school about tolerance is a myth," noted Lipman. Tolerance is a normal and expected outcome of opioid therapy and has not proven to be a limitation to long-term opioid use.

Another term that is gaining in popularity is pseudoaddiction. Strassels defined pseudoaddiction as "when someone acts like they have a substance abuse problem, but the problem is really that their pain is being undertreated." Once the patient's opioid dose is increased to a therapeutic level, then the "addiction" behaviors go away as well. Strassels advises pharmacists not to interpret requests for more medication as drug-seeking behavior and recommends carefully reassessing the patient's pain regimen in order to adequately manage the pain. Table 2 summarizes a pain treatment strategy that can be used by all healthcare providers.

Table 2
ABCs OF PAIN TREATMENT

Results from a survey of phar-macists conducted recently by researchers at the University of Wisconsin, confirmed the need for further education about pain, opioid analgesics, addiction, and controlled-substances policy. Eighty-eight percent of the respondents said addiction means physical dependence and two-thirds (68%) were aware of situations in which pharmacists suspected that patients with inadequately treated pain were "drug seekers" because they had requested additional pain medications.

Dosing appropriately

Unlike the non-opioid analgesics, opioid analgesics do not exhibit a ceiling effect; therefore, the dose can be increased until the desired analgesic effect is obtained or until side effects become intolerable.

"Additional pain requires additional analgesia," said Lipman, adding, "We need to treat patients with a regular schedule [around the clock] to prevent recurrence of pain." He cited that the benefits of long-acting opioids for chronic pain include continuous pain relief, less peak-and-trough effect than is found with short-acting opioids, less sleep disturbance, fewer problems with patient compliance, and fewer reported side effects.

So, if the pharmacist sees a patient is getting a prescription filled for a short-acting agent such as Percocet (oxycodone/acetaminophen) or Vicodin (hydrocodone/acetaminophen) on a continuous basis, Fudin said this would be a good time to confer with the physician about switching the patient to a long-acting formulation of oxycodone or morphine. He also cautioned about the toxicity that can arise from the chronic use of acetaminophen, though these medications should be made available to the patient for breakthrough pain.

Lipman also stressed the need for physicians and pharmacists to know how to appropriately increase the opioid dose to get an appropriate effect. He has seen many physicians give up on opioids because they failed to reach an appropriate level or had increased the opioid dose inadequately.

If the pain is not controlled, then the dose of the opioid should be increased by 50%, said Lipman. For example, if the patient is receiving 20 mg of morphine every four hours and complains of inadequate relief, the next recommended dose is 30 mg every four hours. By the same token, if the patient is on 500 mg morphine every 24 hours and continues to suffer, the next recommended dose is 750 mg. If the physician increases this patient's dose by only 50 mg, Lipman called it "homeopathy."

It is essential for every pharmacist to educate both the patient and physician about appropriate pain management as well as to have a good pain specialist in his or her referral base, which may be necessary if a physician is reluctant to increase the opioid dose appropriately.

How often can you increase the dose by 50%? Every five half-lives, according to Lipman. That could translate to twice a day with oral morphine or every 100 hours with the fentanyl patch.

Balancing act

While the original idea behind polymer formulations of oxycodone was to reduce the likelihood of misuse with high-dose formulations, opiate addicts quickly learned the ease of extracting the molecule from the polymer formula. On the streets, it's known as Oxy or OC, and abusers are crushing and snorting or injecting the drug to get an intense narcotic rush, which sometimes causes death.

The areas hardest hit include Florida, Kentucky, Maine, Virginia, and West Virginia. Lawsuits in Kentucky, Ohio, Virginia, and West Virginia have been filed against Purdue Pharma. Many of the suits claim the drug was deceptively marketed and overprescribed. In statements, Purdue officials have said the claims are "baseless" and have vowed not to let them "deter us from our mission: to ensure patients in pain have the medications they need."

The major source of oxycodone, according to DEA, has been through forged prescriptions and professional diversion through unscrupulous pharmacists, doctors, and dentists. In Tampa, Fla., a pre-pharmacy student pleaded guilty to a manslaughter charge in the OxyContin overdose death of another student. In New Jersey, authorities arrested two Purdue Pharma employees accused of possessing a supply of oxycodone powder with the intent to sell.

Though DEA's tactic to restrict access to the medication may be understandable to some, it has attracted criticism from many in the healthcare community. "Our goal is to help treat pain more effectively, and restricting medication access is not in the best interest of the patient," noted Strassels.

The pharmacists contacted by Drug Topics all agreed that preventing or stopping prescription drug abuse is an important part of patient care. But, they said, it needs to be done in a balanced way that blocks illegal abuse without discouraging the positive, safe, and legal use of opioid medications.

In an editorial, James Campbell, M.D., president and chairman of the board of the American Pain Foundation, wrote "Doctors and pharmacists do need to be diligent in taking security measures to keep opioid medications out of improper hands. Regulators and law enforcement officers should be tough in combating the diversion of opioids into street traffic. But the 'war on drugs' should not be turned into a 'war on patients.' "

Strassels hopes all the sensational media coverage will become the "silver lining in the cloud" by getting everyone to pay more attention to the problem overall. But Rebecca Snead, R.Ph., executive director of the Virginia Pharmacists Association (VPA), cautioned that we have to keep all of this in perspective. "The media and the frequency in which they latched onto this issue have made OxyContin a household word," she commented. "But the drug of today is not going to be the drug of tomorrow."

Instead of limiting access to the drugs, Snead would like to see the money being used to look into this issue go to community services. She pointed out that most of the news reports are coming from economically depressed areas where people are realizing they have a commodity on their hands. These patients are selling their painkillers to bored teenagers, and, in exchange, the patients can pay their rent or put food on the table.

It's been reported that OxyContin abuse first exploded in rural Maine and Appalachia because of the poor economy, a scarcity of cocaine and heroin, and a large population of elderly people who use the drug to relieve the pain of cancer or other illnesses.

The National Association of Attorneys General is assembling a prescription drug abuse task force to develop strategies to stop abuse, particularly of OxyContin. The attorney general of Virginia is exploring instituting a tracking system such as the one already in place in Kentucky. However, Snead said, outcomes of the monitoring system in Kentucky have not resulted in fewer problems, and it doesn't address the root cause of the problem. In addition, privacy rights advocates see the use of a database infringing on the patient's rights, thus making the information vulnerable to unwanted scrutiny.

Pharmacists have also gotten very hesitant about stocking Schedule II drugs, and the increased media attention has led to an increase in the number of robberies. An initiative proposed by VPA involves the ability to electronically order Schedule II drugs, ensuring faster delivery and minimizing the need to overstock these medications.

Purdue Pharma has met with DEA to discuss mutual concerns about the diversion and abuse of OxyContin. In response, Purdue has been rolling out its 10-Point Plan to Reduce Prescription Drug Abuse. Some of the key points include distribution of tamper-resistant prescription pads in problematic areas, such as Maine and Virginia; mailing educational brochures to physicians and R.Ph.s on ways to prevent drug diversion; and sponsoring educational programs for law enforcement officials and continuing medical education programs for healthcare professionals.

The manufacturer has also suspended shipments of the 160-mg dosage of OxyContin, citing concerns about the possibility of illicit use in a dose of that magnitude. Purdue is also looking into ways to reformulate oxycodone as well as developing new painkillers that would be less subject to abuse.

Officials around the country are working with pharmacists, doctors, and hospitals to devise better prescribing systems, such as electronic prescribing, though law enforcement officials acknowledge that no system will ever be foolproof. Lawmakers in Maine have passed a bill that will establish security requirements for written prescriptions for Schedule II drugs, primarily through the use of tamper-proof Rx forms.

The bill also makes it easier to bring forgery charges when bogus forms are used. Failure to disclose recent narcotic prescriptions from other physicians or use of a false name ("doctor shopping") will fall within the definition of deception and will result in serious penalties. Laws in place now tend to give lesser penalties to abusers of prescription drugs than to those who use illegal drugs.

Addiction is a treatable disease

Substantial progress has been made in our knowledge of drug abuse treatment. Research has shown that drug abuse treatment is both effective and cost-effective in reducing not only drug consumption but also the associated health and social consequences.

First and foremost, Schnoll said, "in order to differentiate an addict from someone who is undermedicated, you have to treat the pain aggressively." Addiction is a major, chronic disorder characterized by remission and exacerbations. He added that a pharmacist may be one of the first people to see this problem.

One of the major obstacles in treating addiction, according to Schnoll, is the distribution of federal and state substance abuse funds. "We take the most costly approach to treating the problem—incarceration," he declared. Only 3.7% of the money spent by states on substance abuse goes to prevention, treatment, and research, with the majority going to the criminal justice system. It costs the criminal justice system almost $40,000 a year to incarcerate an addict. The cost of treating the addict in a residential treatment center is about $12,000 per year.

Schnoll feels we need to do a better job of spending the money, by shifting the ratio toward prevention, treatment, and research. "What we are reading in the papers is anecdotal," he said. He has seen an unpublished report that states that of the deaths attributed to OxyContin in Kentucky, only two were actually solely due to the narcotic. All of the others were mixed substance abuse cases. The media, he declared, don't report the abuse in a balanced way and only foster fears and stigmas.

Pharmacological treatment options

Two opiate agonist medications, methadone and LAAM (levo-alpha-acetylmethadol, Orlaam, Roxane Laboratories), have been approved for the treatment of opiate addiction. Methadone was approved for use in 1972, and there are currently an estimated 650 methadone maintenance programs throughout the country.

In 1993, LAAM was approved, and it has the advantage of requiring three doses per week rather than daily doses, thus freeing patients from daily clinic attendance. However, both of these options may present problems pertaining to eventual withdrawal and detoxification. Roxane recently modified the labeling for Orlaam after receiving reports of severe cardiac arrhythmia and has indicated that the drug should not be used as first-line therapy. Experts are beginning to recognize the need for new treatment options for opiate addicts.

Naltrexone (ReVia, DuPont), an orally effective and long-acting opiate antagonist, has been shown to be effective in preventing relapse to opiate addiction in highly motivated patients (e.g., healthcare providers, probationers, parolees) who are under strong external pressure to remain opiate-free. It is not approved for opiate addiction.

DrugAbuse Sciences is developing a controlled-release version of naltrexone (Naltrel) that requires only a monthly injection. The firm hopes that will help overcome the hurdle of addicts failing to follow a drug regimen. Naltrel is in phase III trials.

Buprenorphine (Subutex, Reckitt Benckiser), a partial opiate agonist that produces less physiological dependence than methadone or LAAM, is currently in clinical trials. It has been shown to be effective in maintenance therapy, in retaining patients in treatment, and in facilitating abstinence from illicit opiates. Buprenorphine is being tested in combination with naloxone (Suboxone), a pure narcotic antagonist, in a sublingual preparation to avoid diversion of the product for intravenous abuse. The company already markets the agent under the branded name Buprenex for the treatment of moderate to severe pain.

The new medicines are emerging as federal officials prepare to give physicians more authority to dispense drugs that help addicts. Under the Drug Addiction Treatment Act, "a state may not preclude a practitioner from dispensing or prescribing drugs in Schedule III, IV, or V, or combination of such drugs, to patients for maintenance or detoxification treatment." Opiate-addicted patients would be permitted to fill an Rx for buprenorphine in a pharmacy once the drug receives Food & Drug Administration approval for that use.

By shifting the focus of treatment from methadone clinics, health officials hope to better serve the addict population, who often are reluctant to visit the clinics. Both the Reckitt Benckiser buprenorphine products are "approvable" at FDA, pending resolution of labeling and chemistry/ manufacturing issues.

Pharmacist's responsibilities

"Your responsibilities [as a pharmacist] are first and foremost as a healthcare provider," reflected Snead. Her recipe for successful pain management includes providing optimum patient care, increasing communication time with the prescribing physicians, documenting pertinent information, and educating oneself on the pain guidelines in one's state. The Federation of State Medical Boards has published Model Guidelines for the Use of Controlled Substances for the Treatment of Pain, and many states have adopted the guidelines in whole or in part.

One of the cardinal rules repeated by all the experts is to trust the patient. "If a patient comes in with a story of pain, unless the red flag comes up early, I tend to believe the patient," commented Schnoll. "If the patient is addicted, the patient will reveal the overuse at some point."

DEA has a Web site devoted to its Diversion Control Program; it's available at www.deadiversion.usdoj.gov . The site offers vital information for pharmacists, such as how to recognize the drug abuser, what to do when confronted by a suspected drug abuser, characteristics of forged prescriptions, and types of fraudulent Rxs. Table 3 outlines some of the behavioral characteristics of a drug abuser. It is important to point out that some of the less predictable behaviors may be signs of undertreatment of pain.

Table 3
RECOGNIZING THE DRUG ABUSER

The president of VPA, Timothy Lucas, R.Ph., urged pharmacists to use this approach in his association's April newsletter. "Don't get caught off guard!" he wrote. "We have an inherited skepticism when filling any narcotic prescription, we look for irregularities, we scrutinize, and we do our best to ward off would-be abusers. So, allow your professional judgment to question irregular prescribing, yet also feel comfortable when dispensing for relief of chronic pain."

Remember, advised Strassels, "pharmacists are in a great position to help reinforce the message that [opioids] are good drugs, but, like everything else, they have to be used appropriately."

Tammy Chernin, R.Ph.

Tammy Chernin. PAINKILLERS AND PILL POPPING.

Drug Topics

2001;15:31.