Wednesday, July 26, 2006
Mr. Chairman and Members of the Subcommittee:
What is the Scope of Prescription Drug Abuse in this Country?
Prescription Drugs with Abuse Liability
(1) stimulants, which are prescribed to treat attention-deficit hyperactivity disorder (ADHD) and narcolepsy and include drugs such as Ritalin and Adderall; (2) opioids, which are mostly prescribed to treat moderate to severe pain and include drugs such as OxyContin and Vicodin; and (3) CNS depressants, typically prescribed for the treatment of anxiety, panic, sleep disorders, acute stress reactions, and muscle spasms and include drugs such as Valium, Librium, and Xanax.
To understand how these drugs can have both beneficial effects in patients and serious abuse and health liabilities in people taking them for non-medical reasons requires knowledge of how drugs exert their effects in the brain. As noted above, there can be substantial overlap between the brain systems that mediate the therapeutic effects of psychotropic medications and those responsible for the reinforcing effects of drugs of abuse. However, while the molecular targets in the brain for some medications may be the same ones as those for some of the drugs of abuse, differences in how much of the drug gets into the brain and how fast it gets there determine whether desirable (therapeutic) or undesirable (abuse and addiction) effects will follow. Factors such as drug dosage, route of administration (which regulates the speed of drug delivery to the brain), and user expectations are crucial. For example, the stimulant methylphenidate (Ritalin) has much in common with cocaine-they bind to similar sites in the brain and they both increase the brain chemical dopamine through the same molecular targets. And when both drugs are administered intravenously, they cause a rapid and large increase in dopamine, which a person experiences as a rush or high. However, when methylphenidate is taken orally, as prescribed, it elicits a gradual and sustained increase in dopamine, which is not perceived as euphoria and instead produces the expected therapeutic effects seen in many patients.
Scientists and physicians are learning how to exploit such differences to develop formulations and dosage regimens for optimal therapeutic value and minimal abuse and addiction potential. Unfortunately, these strategies can sometimes be undermined by sophisticated abusers. Consider OxyContin, a pain medication originally marketed as having a low potential for abuse because it was formulated to ensure a slow and gradual release of the drug. Abusers quickly learned that the pills could be crushed and their contents injected or snorted, releasing the entire dosage at once. What abusers do not realize is the great risk of overdose and other devastating consequences that may result from this practice. Now widespread in its abuse, OxyContin is the only commonly prescribed opioid analgesic that comes with a "black box" warning.
Why is this happening now?
Notably, between 1987 and 1996, a nearly four-fold increase occurred in the prevalence of stimulant prescriptions among youth; this increase has persisted, but has since remained near the 1996 levels. Similarly, the number of oxycodone and hydrocodone prescriptions has more than doubled between 1994 and 2001. While such increases in psychoactive drug prescriptions reflect improved diagnostic practices and treatment options, it would be naive not to also consider the contribution of market forces in the emergence of these trends. For example, sales of ADHD medications in the United States reached $3.1 billion in 2004. But even at this robust level of sales, the number of prescriptions for ADHD medications is less than 20 percent when compared to the 120 million prescriptions written in 2005 for pain medications containing hydrocodone or oxycodone. Such high exposure rates suggest that we need to discover the potential abuse consequences for youth and other populations at risk for addiction.
Special populations, specific risks and consequences
Today we know that the last part of the brain to fully mature is the prefrontal cortex, a region that governs judgment and decision-making functions. This may help explain why teens are prone to risk-taking and why high rates of risky behaviors, including abuse of alcohol and other drugs, have been reported among those who abuse prescription drugs. The 2001 NSDUH survey reveals that youth who had used prescription drugs non-medically in the past year were almost four times more likely to have also used other illicit drugs.
We are also particularly concerned about older Americans, who currently make up only 13 percent of the population but who receive approximately one-third of all medications prescribed in the Nation. For practical reasons, older patients are sometimes prescribed long-term and multiple prescriptions, which could lead to abuse or unintentional misuse. These medications can interact with over-the-counter medicines and dietary supplements, which older adults tend to consume in significant quantities. Older adults also experience higher rates of other illnesses, normal changes in drug metabolism, and increased susceptibility to toxic effects. It is hardly surprising then that abuse or unintentional misuse of prescription drugs by elderly persons could lead to more severe health consequences. For example, elderly persons who take benzodiazepines such as Valium, Librium, and Xanax are at increased risk for cognitive impairment, leading to possible falls as well as vehicular accidents. Moreover, not all physicians know that prescribing benzodiazepines to elderly people is contraindicated for these reasons. Therefore, physician education is a necessary part of any effort to curb the abuse of prescription medications.
Prescription drug abuse must also be carefully tracked among women because of their combined vulnerabilities. First, women are more likely than men to suffer from depression, anxiety, trauma, and victimization, all of which frequently appear with substance abuse in the form of comorbidities. Second, girls and women report using drugs to cope with stressful situations in their lives. Third, studies suggest that women are significantly more likely than men to be prescribed an abusable drug, particularly in the form of narcotics and anti-anxiety medications. These cumulative risks notwithstanding, adult men and women have roughly similar rates of non-medical use of prescription drugs; 12-17-year-old girls, however, are more likely than boys to abuse psychotherapeutic drugs, including stimulants.
In addition to the risk to women is the potential for harm to the developing fetus. Therefore, more research is needed on the extent and patterns of prescription drug abuse during pregnancy. National projections from survey data collected between 2002 and 2004 suggest that 109,000 pregnant women abused pain relievers in the past year. And past-year abuse of any stimulants (including methamphetamine) or sedatives/tranquilizers was reported by 32,000 and 56,000 pregnant women, respectively. However, there is overall less non-medical abuse of prescription psychotherapeutics among pregnant than among non-pregnant women (6% and 9.3%, respectively), although this is not the case in pregnant adolescent girls (15-17 years), in whom the rate of prescription drug abuse is higher than in those who are not pregnant.
What Abuse of Prescription Drugs Does to the Brain and Body
What is NIDA doing about it?
Epidemiology and surveillance
Another important initiative pertains to the development of new pain medications or formulations with minimum abuse potential. We have witnessed some remarkable advances in this area of research recently with the introduction of buprenorphine/naloxone, a combined formulation for the treatment of opiate addiction with dramatically reduced abuse liability. Compounds that act on a combination of two distinct opioid receptors (mu and delta), have been shown in preclinical studies to induced strong analgesia without producing tolerance or dependence. Researchers are also getting closer to developing a new generation of non-opioid-based medications for severe pain that would circumvent the brain reward pathways, greatly reducing abuse potential. Included are compounds that work through a cannabinoid receptor subtype located primarily in the peripheral nervous system.
Treatment and Prevention
Although scientifically validated prevention programs have been shown to be effective in curbing the prevalence of substance abuse and addiction in general, non-medical use of prescription drugs in some ways presents a more difficult scenario than illicit drugs. Because prescription drugs are safe and effective when used properly and are broadly marketed to the public, the notion that they are also harmful and addictive when abused can be a difficult one to convey. Thus, we need focused research to discover targeted communication strategies that effectively address this problem. Reaching this goal may be significantly more complex and nuanced than developing and deploying effective programs for the prevention of abuse of illicit drugs, but good prevention messages based on scientific evidence will be hard to ignore and will make their mark in time.
In the meantime, the centerpiece of our strategy to curtail the prevalence of prescription drug abuse must center around our efforts to disseminate accurate information about the serious health consequences involved, with particular focus on addiction potential. Our messages aim to reach not only the general public and populations at heightened risk, such as adolescents, but also physicians and other health care providers, whose training on proper diagnostic and monitoring practices is vitally important. We will continue our close collaborations with physicians' organizations, the Office of National Drug Control Policy (ONDCP), SAMHSA and other Federal agencies, as well as professional associations with a strong interest in preserving public health. We regard these preventive efforts an integral part of NIDA's mission.
Perhaps one of the most challenging aspects of this trend is that prescription drug abuse affects individuals of all ages. On the other hand, we are fortunate to have in place an efficient warning system that has helped us to spot this problem at a relatively early stage and to quickly implement activities designed to keep it in check. Consistent with one of NIDA's most important goals, our response has been framed by our commitment to translate what we know from research to help the public better understand drug abuse and addiction, and to develop more effective strategies for their prevention and treatment.
The emerging nature of the prescription drug abuse problem, combined with our substantial but still growing knowledge of its underlying causes and resulting consequences, make us optimistic about our chances to rationally and successfully address this challenge.
Thank you for allowing me to share this information with you. I will be happy to answer any questions you may have.
1 See, e.g., Zacny et. al., College on Problems of Drug Dependence taskforce on Prescription Opioid Non-Medical Use and Abuse: Position Statements, Drug and Alcohol Dependence 69 (2003) 25-232; and Compton and Volkow, Major Increases in Opioid Analgesic Abuse in the U.S.: Concerns and Strategies, Drug and Alcohol Dependence 81 (2006) 103-107. These citations include information from IMS Health's National Prescription Audit.
Last Revised: July 27, 2006