MEDICATIONS: PRESCRIPTION DRUGS: ABUSE AND ADDICTION

Although most people take prescription medications responsibly, there has been an increase in the nonmedical use of or, as the National Institute on Drug Abuse, a part of the National Institutes of Health, refers to it in this report, abuse1 of prescription drugs in the United States.

Although many prescription drugs can be abused, there are several classifications of medications that are commonly abused.

The three classes of prescription drugs that are most commonly abused are:

· Opioids, which are most often prescribed to treat pain;

· Central nervous system (CNS) depressants, which are used to treat anxiety and sleep disorders; and

· Stimulants, which are prescribed to treat the sleep disorder narcolepsy and attention-deficit hyperactivity disorder (ADHD).

Opioids are commonly prescribed because of their effective analgesic, or pain-relieving, properties. Medications that fall within this class — referred to as prescription narcotics — include morphine (e.g., Kadian, Avinza), codeine, oxycodone (e.g., OxyContin, Percodan, Percocet) and related drugs. Morphine, for example, often is used before and after surgical procedures to alleviate severe pain. Codeine, on the other hand, often is prescribed for mild pain. In addition to their pain-relieving properties, some of these drugs — codeine and diphenoxylate (Lomotil), for example — can be used to relieve coughs and diarrhea.

Opioids act on the brain and body by attaching to specific proteins called opioid receptors, which are found in the brain, spinal cord and gastrointestinal tract. When these drugs attach to certain opioid receptors, they can block the perception of pain. Opioids can produce drowsiness, nausea, constipation and, depending upon the amount of drug taken, depress respiration. Opioid drugs also can induce euphoria by affecting the brain regions that mediate what we perceive as pleasure. This feeling often is intensified for those who abuse opioids when administered by routes other than those recommended. For example, OxyContin often is snorted or injected to enhance its euphoric effects, while at the same time increasing the risk for serious medical consequences, such as opioid overdose.2

Taken as directed, opioids can be used to manage pain effectively. Many studies have shown that the properly managed, short-term medical use of opioid analgesic drugs is safe and rarely causes addiction — defined as the compulsive and uncontrollable use of drugs despite adverse consequences — or dependence, which occurs when the body adapts to the presence of a drug and often results in withdrawal symptoms when that drug is reduced or stopped. Withdrawal symptoms include restlessness, muscle and bone pain, insomnia, diarrhea, vomiting, cold flashes with goose bumps ("cold turkey") and involuntary leg movements. Long-term use of opioids can lead to physical dependence and addiction. Taking a large single dose of an opioid could cause severe respiratory depression that can lead to death.

Only under a physician's supervision can opioids be used safely with other drugs. Typically, they should not be used with other substances that depress the CNS, such as alcohol, antihistamines, barbiturates, benzodiazepines or general anesthetics, because these combinations increase the risk of life-threatening respiratory depression.

1 A common vocabulary has not been established in the field of prescription drug abuse. Because much of the data collected in this area focuses on nonmedical use of prescription drugs, the definition of abuse used in this report does not correspond to the definition of abuse/dependence listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM).

2 This does not apply only to opioids. Changes in routes of administration also contribute to the abuse of other prescription medications, and this practice can lead to serious medical consequences.

CNS depressants, sometimes referred to as sedatives and tranquilizers, are substances that can slow normal brain function. Because of this property, some CNS depressants are useful in the treatment of anxiety and sleep disorders. Among the medications that are commonly prescribed for these purposes are the following:

· Barbiturates, such as mephobarbital (Mebaral) and pentobarbital sodium (Nembutal), are used to treat anxiety, tension and sleep disorders.

· Benzodiazepines, such as diazepam (Valium), chlordiazepoxide HCl (Librium) and alprazolam (Xanax), are prescribed to treat anxiety, acute stress reactions and panic attacks. The more sedating benzodiazepines, such as triazolam (Halcion) and estazolam (ProSom) are prescribed for short-term treatment of sleep disorders. Usually, benzodiazepines are not prescribed for long-term use.

There are numerous CNS depressants; most act on the brain by affecting the neurotransmitter gammaaminobutyric acid (GABA). Neurotransmitters are brain chemicals that facilitate communication between brain cells. GABA works by decreasing brain activity. Although the different classes of CNS depressants work in unique ways, it is through their ability to increase GABA activity that they produce a drowsy or calming effect that is beneficial to those suffering from anxiety or sleep disorders.

Despite their many beneficial effects, barbiturates and benzodiazepines have the potential for abuse and should be used only as prescribed. During the first few days of taking a prescribed CNS depressant, a person usually feels sleepy and uncoordinated, but as the body becomes accustomed to the effects of the drug, these feelings begin to disappear. If one uses these drugs long term, the body will develop tolerance for the drugs, and larger doses will be needed to achieve the same initial effects. Continued use can lead to physical dependence and — when use is reduced or stopped — withdrawal. Because all CNS depressants work by slowing the brain's activity, when an individual stops taking them, the brain's activity can rebound and race out of control, potentially leading to seizures and other harmful consequences. Although withdrawal from benzodiazepines can be problematic, it is rarely life threatening, whereas withdrawal from prolonged use of other CNS depressants can have life-threatening complications. Therefore, someone who is thinking about discontinuing CNS depressant therapy or who is suffering withdrawal from a CNS depressant should speak with a physician or seek medical treatment.

CNS depressants should be used in combination with other medications only under a physician's close supervision. Typically, they should not be combined with any other medication or substance that causes CNS depression, including prescription pain medicines, some OTC cold and allergy medications, and alcohol. Using CNS depressants with these other substances — particularly alcohol — can slow both the heart and respiration and may lead to death.

As the name suggests, stimulants increase alertness, attention and energy, as well as elevate blood pressure and increase heart rate and respiration. Stimulants historically were used to treat asthma and other respiratory problems, obesity, neurological disorders and a variety of other ailments. But as their potential for abuse and addiction became apparent, the medical use of stimulants began to wane. Now, stimulants are prescribed for the treatment of only a few health conditions, including narcolepsy, ADHD and depression that has not responded to other treatments.

Stimulants, such as dextroamphetamine (Dexedrine and Adderall) and methylphenidate (Ritalin and Concerta), have chemical structures similar to a family of key brain neurotransmitters called monoamines, which include norepinephrine and dopamine. Stimulants enhance the effects of these chemicals in the brain. Stimulants also increase blood pressure and heart rate, constrict blood vessels, increase blood glucose, and open up the pathways of the respiratory system. The increase in dopamine is associated with a sense of euphoria that can accompany the use of these drugs.

As with other drugs of abuse, it is possible for individuals to become dependent upon or addicted to many stimulants. Withdrawal symptoms associated with discontinuing stimulant use include fatigue, depression and disturbance of sleep patterns. Repeated use of some stimulants over a short period can lead to feelings of hostility or paranoia. Further, taking high doses of a stimulant may result in dangerously high body temperature and an irregular heartbeat. There also is the potential for cardiovascular failure or lethal seizures.

Stimulants should be used in combination with other medications only under a physician's supervision. Patients also should be aware of the dangers associated with mixing stimulants and OTC cold medicines that contain decongestants; combining these substances may cause blood pressure to become dangerously high or lead to irregular heart rhythms.

Although prescription drug abuse affects many Americans, some concerning trends can be seen among older adults, adolescents and women. Several indicators suggest that prescription drug abuse is on the rise in the United States. According to the 2003 National Survey on Drug Use and Health (NSDUH), an estimated 4.7 million Americans used prescription drugs nonmedically for the first time in 2002:

· 2.5 million used pain relievers

· 1.2 million used tranquilizers

· 761,000 used stimulants

· 225,000 used sedatives

Pain reliever incidence increased — from 573,000 initiates in 1990 to 2.5 million initiates in 2000 — and has remained stable through 2003. In 2002, more than half (55 percent) of the new users were females, and more than half (56 percent) were ages 18 or older.

The Drug Abuse Warning Network (DAWN), which monitors medications and illicit drugs reported in emergency departments (EDs) across the nation, recently found that two of the most frequently reported prescription medications in drug abuse-related cases are benzodiazepines (e.g., diazepam, alprazolam, clonazepam and lorazepam) and opioid pain relievers (e.g., oxycodone, hydrocodone, morphine, methadone, and combinations that include these drugs). In 2002, benzodiazepines accounted for 100,784 mentions that were classified as drug abuse cases, and opioid pain relievers accounted for more than 119,000 ED mentions. From 1994 to 2002, ED mentions of hydrocodone and oxycodone increased by 170 percent and 450 percent, respectively. While ED visits attributed to drug addiction and drug-taking for psychoactive effects have been increasing, intentional overdose visits have remained stable since 1995.

Persons 65 years of age and above comprise only 13 percent of the population, yet account for approximately one-third of all medications prescribed in the United States. Older patients are more likely to be prescribed long-term and multiple prescriptions, which could lead to unintentional misuse.

The elderly also are at risk for prescription drug abuse, in which they intentionally take medications that are not medically necessary. In addition to prescription medications, a large percentage of older adults also use OTC medicines and dietary supplements. Because of their high rates of comorbid illnesses, changes in drug metabolism with age and the potential for drug interactions, prescription and OTC drug abuse and misuse can have more adverse health consequences among the elderly than are likely to be seen in a younger population. Elderly persons who take benzodiazepines are at increased risk for cognitive impairment associated with benzodiazepine use, leading to possible falls (causing hip and thigh fractures), as well as vehicle accidents. However, cognitive impairment may be reversible once the drug is discontinued.

Data from the 2003 NSDUH indicate that 4.0 percent of youth ages 12 to 17 reported nonmedical use of prescription medications in the past month. Rates of abuse were highest among the 18-25 age group (6.0 percent). Among the youngest group surveyed, ages 12-13, a higher percentage reported using psychotherapeutics (1.8 percent) than marijuana (1.0 percent).

The NIDA Monitoring the Future survey of 8th, 10th and 12th graders found that the nonmedical use of opioids, tranquilizers, sedatives/barbiturates, and amphetamines was unchanged between 2003 and 2004. Specifically, the survey found that 5.0 percent of 12th graders reported using OxyContin without a prescription in the past year, and 9.3 percent reported using Vicodin, making Vicodin one of the most commonly abused licit drugs in this population. Past year, nonmedical use of tranquilizers (e.g., Valium, Xanax) in 2004 was 2.5 percent for 8th graders, 5.1 percent for 10th graders and 7.3 percent for 12th graders. Also within the past year, 6.5 percent of 12th graders used sedatives/ barbiturates (e.g., Amytal, Nembutal) nonmedically and 10.0 percent used amphetamines (e.g., Ritalin, Benzedrine).

Youth who use other drugs are more likely to abuse prescription medications. According to the 2001 National Household Survey on Drug Abuse (now the NSDUH), 63 percent of youth who had used prescription drugs nonmedically in the past year had also used marijuana in the past year, compared with 17 percent of youth who had not used prescription drugs nonmedically in the past year.

Studies suggest that women are more likely than men to be prescribed an abusable prescription drug, particularly narcotics and antianxiety drugs — in some cases, 55 percent more likely.

Overall, men and women have roughly similar rates of nonmedical use of prescription drugs. An exception is found among 12- to 17-year-olds. In this age group, young women are more likely than young men to use psychotherapeutic drugs nonmedically. In addition, research has shown that women are at increased risk for nonmedical use of narcotic analgesics and tranquilizers (e.g., benzodiazepines).

The risks for addiction to prescription drugs increase when the drugs are used in ways other than for those prescribed. Health care providers, primary care physicians and pharmacists, as well as patients themselves, all can play a role in identifying and preventing prescription drug abuse.

· Physicians. Because about 70 percent of Americans (approximately 191 million people) visit their primary care physician at least once every two years, these doctors are in a unique position — not only to prescribe medications but also to identify prescription drug abuse when it exists, help the patient recognize the problem, set recovery goals and seek appropriate treatment. Screening for prescription drug abuse can be incorporated into routine medical visits by asking about substance abuse history, current prescription and OTC use, and reasons for use. Doctors should take note of rapid increases in the amount of medication needed, or frequent, unscheduled refill requests. Doctors also should be alert to the fact that those addicted to prescription drugs may engage in "doctor shopping" — moving from provider to provider in an effort to obtain multiple prescriptions for the drug(s) they abuse.

Preventing or stopping prescription drug abuse is an important part of patient care. However, health care providers should not avoid prescribing or administering stimulants, CNS depressants or opioid pain relievers if needed.

· Pharmacists. By providing clear information on how to take a medication appropriately and describing possible side effects or drug interactions, pharmacists also can play a key role in preventing prescription drug abuse. Moreover, by monitoring prescriptions for falsification or alterations and being aware of potential "doctor shopping," pharmacists can be the first line of defense in recognizing prescription drug abuse. Some pharmacies have developed hotlines to alert other pharmacies in the region when a fraudulent prescription is detected.

· Patients. There also are steps a patient can take to ensure that they use prescription medications appropriately. Patients should always follow the prescribed directions, be aware of potential interactions with other drugs, never stop or change a dosing regimen without first discussing it with their health care provider, and never use another person's prescription. Patients should inform their health care professionals about all the prescription and OTC medicines and dietary and herbal supplements they are taking, in addition to a full description of their presenting complaint, before they obtain any other medications.

About 70 percent of Americans — approximately 191 million people — visit a health care provider, such as a primary care physician, at least once every two years. Thus, health care providers are in a unique position not only to prescribe needed medications appropriately but also to identify prescription drug abuse when it exists and help the patient recognize the problem, set goals for recovery and seek appropriate treatment when necessary. Screening for any type of substance abuse can be incorporated into routine history taking with questions about what prescriptions and over-the-counter medicines the patient is taking and why. Screening also can be performed if a patient presents with specific symptoms associated with problem use of a substance.

Over time, providers should note any rapid increases in the amount of a medication needed — which may indicate the development of tolerance — or frequent requests for refills before the quantity prescribed should have been used. They also should be alert to the fact that those addicted to prescription medications may engage in "doctor shopping," moving from provider to provider in an effort to get multiple prescriptions for the drug they abuse.

Preventing or stopping prescription drug abuse is an important part of patient care. However, health care providers should not avoid prescribing or administering strong CNS depressants and painkillers, if they are needed.

Pharmacists can play a key role in preventing prescription drug misuse and abuse by providing clear information and advice about how to take a medication appropriately, about the effects the medication may have, and about any possible drug interactions. Pharmacists can help prevent prescription fraud or diversion by looking for false or altered prescription forms. Many pharmacies have developed "hotlines" to alert other pharmacies in the region when a fraud is detected.

There are several ways that patients can prevent prescription drug abuse. When visiting the doctor, provide a complete medical history and a description of the reason for the visit to ensure that the doctor understands the complaint and can prescribe appropriate medication. If a doctor prescribes a pain medication, stimulant or CNS depressant, follow the directions for use carefully and learn about the effects that the drug could have, especially during the first few days during which the body is adapting to the medication. Also be aware of potential interactions with other drugs by reading all information provided by the pharmacist. Do not increase or decrease doses or abruptly stop taking a prescription without consulting a health care provider first. For example, if you are taking a pain reliever for chronic pain and the medication no longer seems to be effectively controlling the pain, speak with your physician; do not increase the dose on your own. Finally, never use another person's prescription.

Years of research have shown us that addiction to any drug (illicit or prescribed) is a brain disease that, like other chronic diseases, can be treated effectively. No single type of treatment is appropriate for all individuals addicted to prescription drugs. Treatment must take into account the type of drug used and the needs of the individual. Successful treatment may need to incorporate several components, including detoxification, counseling and in some cases, the use of pharmacological therapies. Multiple courses of treatment may be needed for the patient to make a full recovery.

The two main categories of drug addiction treatment are behavioral and pharmacological. Behavioral treatments encourage patients to stop drug use and teach them how to function without drugs, handle cravings, avoid drugs and situations that could lead to drug use and handle a relapse should it occur. When delivered effectively, behavioral treatments — such as individual counseling, group or family counseling, contingency management and cognitive-behavioral therapies also can help patients improve their personal relationships and their ability to function at work and in the community.

Some addictions, such as opioid addiction, can be treated with medications. These pharmacological treatments counter the effects of the drug on the brain and behavior, and can be used to relieve withdrawal symptoms, treat an overdose or help overcome drug cravings. Although a behavioral or pharmacological approach alone may be effective for treating drug addiction, research shows that, at least in the case of opioid addiction, a combination of both is most effective.

Treating Addiction to Prescription Opioids
Several options are available for effectively treating prescription opioid addiction. These options are drawn from research regarding the treatment of heroin addiction, and include medications such as naltrexone, methadone and buprenorphine, as well as behavioral counseling approaches.

Naltrexone is a medication that blocks the effects of opioids and is used to treat opioid overdose and addiction. Methadone is a synthetic opioid that blocks the effects of heroin and other opioids, eliminates withdrawal symptoms and relieves drug craving. It has been used successfully for more than 30 years to treat heroin addiction. The U.S. Food and Drug Administration approved buprenorphine in October 2002, after more than a decade of research supported by NIDA. Buprenorphine, which can be prescribed by certified physicians in an office setting, is long lasting, less likely to cause respiratory depression than other drugs, and is well tolerated. However, more research is needed to determine the effectiveness of these medications for the treatment of prescription drug abuse.

A useful precursor to long-term treatment of opioid addiction is detoxification. Detoxification in itself is not a treatment. Rather, its primary objective is to relieve withdrawal symptoms while the patient adjusts to being drug-free. To be effective, detoxification must precede long-term treatment that either requires complete abstinence or incorporates a medication, such as methadone or buprenorphine, into the treatment program.

Treating Addiction to CNS Depressants
Patients addicted to barbiturates and benzodiazepines should not attempt to stop taking them on their own. Withdrawal symptoms from these drugs can be problematic, and in the case of certain CNS depressants— potentially life-threatening. Although no research regarding the treatment of barbiturate and benzodiazepine addiction exists, addicted patients should undergo medically supervised detoxification because the treatment dose must be gradually tapered. Inpatient or outpatient counseling can help the individual during this process. Cognitive-behavioral therapy, which focuses on modifying the patient's thinking, expectations, and behaviors, while at the same time increasing skills for coping with various life stressors, also has been used successfully to help individuals adapt to the discontinuation of benzodiazepines.

Often barbiturate and benzodiazepine abuse occurs in conjunction with the abuse of another substance or drug, such as alcohol or cocaine. In these cases of polydrug abuse, the treatment approach must address the multiple addictions.

Treating Addiction to Prescription Stimulants
Treatment of addiction to prescription stimulants, such as Ritalin, is often based on behavioral therapies that have proven effective in treating cocaine and methamphetamine addiction. At this time, there are no proven medications for the treatment of stimulant addiction. However, NIDA is supporting a number of studies on potential medications for treating stimulant addiction.

Depending on the patient's situation, the first steps in treating prescription stimulant addiction may be tapering the drug dosage and attempting to ease withdrawal symptoms. The detoxification process could then be followed by one of many behavioral therapies. Contingency management, for example, uses a system that enables patients to earn vouchers for drug-free urine tests. (These vouchers can be exchanged for items that promote healthy living.) Cognitive-behavioral therapy also may be an effective treatment for addressing stimulant addiction. Finally, recovery support groups may be helpful in conjunction with behavioral therapy.

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