Prescription Drug Abuse

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Unfavorable responses to medical treatments—addiction to prescribed drugs or to those used in treatments—is termed iatrogenic. A wide array of medicines can be associated with addiction or abuse in some people. Such drugs include the OPIOIDS, antihistamines, anticholinergies, and steroids, among others—but the most common are those prescribed for psychological problems.

Some drugs acting on the mind have a low potential for abuse and dependence, for example, the ANTIPSYCHOTICS, antidepressants, and lithium salts. Others, such as the BARBITURATES and AMPHETAMINES, have a high potential.

Although barbiturates are more or less obsolete as tranquilizers and sleeping tablets, addiction to them is still encountered. TOLERANCE AND PHYSICAL DEPENDENCE can rapidly occur during therapy—and abrupt withdrawal can result in a severe and life-threatening withdrawal state. Studies in abusers show them to greatly prefer barbiturates to BENZODIAZEPINES, which have replaced them pharmacologically and are discussed below. MEPROBAMATE, a carbonate used as a tranquilizer, is similar in many ways to the barbiturates, including its abuse potential.

Clinically, patterns of nonmedical use of nonopioids vary greatly; large quantities can be injected into a vein or muscle, often producing abscess formation. Other users take large amounts by mouth, on a binge or spree basis, the most popularbeing pentobarbital, amylbarbital, quinalbarbital, and Tuinal—the amylbarbital/quinalbarbital combination. Some users become permanently intoxicated and totally engrossed in maintaining their supply, licit or illicit. POLYDRUG use in combination with amphetamines or opioids is common.

Withdrawal can be hazardous, with the risk of SEIZURES or psychotic features, when discontinuing chronic usage of 500 milligrams a day or more. Withdrawal DELIRIUM (similar to DELIRIUM TREMENS, DTs) is common and often difficult to treat; a chronic state with HALLUCINATIONS may ensue.

The benzodiazepines supplanted the barbiturates because they seemed to be at least as effective, with few side effects and less likelihood of producing addiction. Benzodiazepines are preferred to placebo by drug abusers but vary in this regard; for example, diazepam (Valium) and lorazepam (Ativan) seem more likely to be taken than is oxazepam (Serax or Serehid). Benzodiazepines have been abused in various countries at various times. They have been injected as the main drug of abuse or as part of a polydrug-abuse pattern. Abusers of alcohol may also abuse benzodiazepines, finding that with drug interaction a potentiation occurs, that is, the combination is particularly powerful. Most benzodiazepine abuse is with drugs obtained legally from a number of complaisant prescribers, but the very heavy user may have to resort to illicit sources of supply. About 50 percent of abusers of benzodiazepines were introduced to the drug within the medical context.

Within polydrug abuse, the benzodiazepine is used to eke out the supply of opioid or to ease the crash from the high euphoria of COCAINE use. Patterns of usage and beliefs about the possible effects of benzodiazepine use vary widely among hard-drug abusers, but, generally speaking, benzodiaze-pines are viewed as potential drugs of dependence in their own right and not as relatively innocuous adjuncts.

It is fairly uncommon for patients started on benzodiazepines for therapeutic purposes to increase their dosage steadily. Nevertheless, since benzodiazepine use is widespread, high-dose users are seen fairly often. It is unclear why some patients escalate their dosage, whereas most remain at therapeutic levels indefinitely.

Amphetamines are stimulants, which raise mood, increase the sense of well-being, energy, and alertness, and decrease appetite. Some few users, paradoxically, become the opposite—drowsy, anxious, and irritable.

Normal-dose usage was typically prescribed; an obese, middle-aged, mildly depressed housewife might have taken two or three doses every day as a pick-me-up, a mild stimulant and appetite suppressant. (Some weak physical dependence ensued from such use, mainly seen as sleep changes on withdrawal.) With the discouragement of such indications, usage by physicians and patients has fallen off. Another obsolete use was as a vigilance-enhancer in those who felt the need to keep awake for excessively long periods, such as medical interns or long-distance truck drivers. Few people progressed from iatrogenic oral misuse to intravenous abuse.

Intravenous amphetamine produces euphoria, similar to but more sustained than that following the use of cocaine. Alter a few hours, the effects wear off, leaving the abuser feeling exhausted, drowsy, and depressed. Clandestine laboratories manufacturing amphetamine are still at work. Their preferred substance is METHAMPHETAMINE, which can be synthesized easily. Since intravenous use of methamphetamine is usual, and tolerance quickly occurs, larger and more frequent doses become required to achieve the desired effect. Toxic effects supervene, with repetitive face and hand movements and stereotyped behavior—for example, the user assembling and dismantling mechanical objects. A full-blown paranoid type of psychosis may develop, with loss of reality and delusions of persecution. Individual susceptibility to these toxic effects varies greatly. Polydrug abuse of amphetamines is common; co-administration of amphetamine with heroin ("speedball") or a barbiturate is believed to optimize the pleasurable effects while minimizing the toxic ones.

Appetite suppressants cover a range of compounds, from the decongestant phenylpropanolamine (often available without prescription), to powerful amphetamine analogues (chemical variants). Most are stimulant, althoughone, fenfluramine, is quite sedative. As with the amphetamines, patterns of use and abuse vary a great deal, from chronic daily ingestion of a therapeutic dose to binge or spree use of large quantities. As a general rule, the more amphetamine-like the appetite suppressant, the more likely it is to be abused.

Trying to stop the use of appetite suppressants may be difficult for abusers, because of withdrawal symptoms such as tiredness, dysphoria (discom-fort), or frank depression. These problems and growing doubts about sustained effectiveness (for their original dietary purposes) have led many doctors to cease prescribing them.

In the early to mid-1990's, two prescription diet drugs, fenfluramine (often taken with phentermine and popularly known as fen-phen) and dexfenfluramine (Redux), grew in popularity. These drugs stimulated production of the brain chemical serotonin, creating a feeling of satiety. Stories in the news media hailed fen-phen and Redux as a miracle cure for obesity. By 1996, millions of prescriptions had been written for the diet pills.

In 1997, reports of heart valve disease in women taking fen-phen or Redux began to surface. The New England Journal of Medicine published a study by doctors at the Mayo Clinic that reported twenty-four women taking fen-phen developed symptomatic heart valve disorders. At the same time, the Food and Drug Administration issued a Public Health Advisory reporting the Mayo Clinic findings and reporting that it had received reports of thirty-six cases of unusual heart valve abnormalities in women ages 30 to 72 taking fenfluramine or dexfenfluramine.

By September 1997, the drugs dexfenfluramine and fenfluramine were withdrawn from the U.S. market by their manufacturer, American Home Products. In December 1999, the company agreed to compensate thousands of people who took either drug in a $3.75 billion dollar settlement of a nationwide class action suit.

Since 1997, subsequent studies have confirmed a causal link between fenfluramines and valve disorders. There is also persuasive evidence of a significant duration effect. In a 1998 study of more than 17,000 obese patients in the United Kingdom, 92 percent of the patients with symptomatic valve disorders had used fenfluramines for more than 3 months. For those who took fen-phen or Redux for less than 3 months, the risk of heart valve disorders appears to be minimal.

Iatrogenic Addiction; Obesity)

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