without inducing the degree of drowsiness which other agents such as barbiturates cause. While at first they were not thought to produce physiological dependence and true addiction, it is now clear that with prolonged usage and/or high dosage, physiological dependence of the type known to occur with barbiturate drugs is produced. This is most clearly seen with several compounds of the substituted diols subclass.

The antidepressant class of drugs was introduced a few years after the major and minor tranquilizers. Imipramine, a drug from the tricyclic series, was first investigated as a potential major tranquilizer but instead was found to be effective in the treatment of depression, especially of the endogenous type. Side effects are generally mild and include dry mouth, blurred vision, and orthostatic hypotension. If tricyclic antidepressants are given concurrently with drugs from the MAO (monoamine oxidase inhibitor) subclass, there have been occasions when there was a marked drug interaction and a toxic state leading to death occurred. It is also known that eating foods which are high in certain amines such as tyramine while receiving MAO inhibitors can lead to a marked hypertension resulting in a cardiovascular accident and death. Physiological dependence does not occur with this class of drugs.

The stimulant class of drugs of which amphetamines constitute the bulk are primarily used in the treatment of obesity but have marked central nervous system effects in increasing activity and reducing fatigue and are used to some extent in the treatment of symptoms of depression. These drugs have recently been subject to marked illicit use and when taken in high enough quantities lead to a psychotic paranoid state. Psychological deper.dence and minor physiological dependence have been demonstrated.

The sedative class of drugs is primarily composed of the long- and intermediate-acting barbiturates. They have been available for a long period of time and were used extensively as antianxiety and calming agents before the introduction of the major and minor tranquilizers. Drowsiness is a common side effect and physiological and psychological dependence does

occur.

The hypnotic class of drugs is used for the treatment of sleep disturbances. Both the barbiturate and non-barbiturate subclasses, when taken in large amounts, produce marked intoxication and depression of respiration which can result in death. Likewise, they produce marked psychological and physiological dependence. The withdrawal syndrome seen after stopping these drugs in physiologically-dependent

individuals is extremely severe and can also lead to death.

These briefly are the classes of drugs we will deal with in today's presentation.

A Model and Sources of Data Necessary to
Characterize the Nature and Extent of
Psychotropic Drug Use

At the time we were invited to testify, it was indicated that a major focus of these hearings was to try to ascertain whether psychotropic drugs were being over-prescribed and over-used in the United States. Certainly this concern has been expressed frequently in the mass media and is an important issue to consider. Unfortunately, this issue is more easily raised than answered if conclusions are to be documented and factual rather than opinionated and judg. mental. For the past 3 years Dr. Mitchell Balter, Chief of the Special Studies Section of the Psychopharmacology Research Branch, has been formulating precise questions about the extent and character of psychotropic drug use and has been collecting the extensive data that are required to provide accurate and comprehensive answers to these questions at the national level. The work is still in progress but some answers are currently available and will be presented today.

The critical questions are fairly simple: To whom are psychotropic drugs being prescribed? By whom are psychotropic drugs being prescribed? For what purposes are psychotropic drugs being prescribed? In what manner are they being prescribed? And, finally, in what manner are they being used by the patient? Several sources of data and types of infor mation are needed to answer these questions satisfactorily. In our working model the physician is viewed as a gatekeeper who issues a prescription to a patient who then has a number of options. He may go on and fill that prescription at a drugstore or elsewhere, or he may not. He may not use all the medication provided in the original prescription or he may not obtain all the refills permitted. Given the range of possibili. ties, it becomes necessary to study the prescribing behavior of the physician and to gather accurate information on drugstore outflow. It is also crucial to obtain information directly from patients, former patients, and others in the general population who are using psychotropic drugs, whatever the source. This requires a broadly based survey approach because the individual can move about from place to place, can change physicians, can borrow drugs, or buy them

Icitly or licitly without consulting a physician. Without obtaining information on the pattern of use directly from the individual, the true significance and character of the drug use cannot be assessed. Through a series of studies supported by contracts and grants and analyses conducted within the Institute, a large body of information on physicians' prescribing, drugstore outflow and patients' and others' use of drugs is being steadily developed. It is from these carefully coordi nated ongoing activities that the data to be presented today have been derived.

Extent Use of Psychotropic Agents

Initially let us consider a representative period and characterize prescription drug use during a single year. In 1967 i is estimated that a total of 1.1 billion prescriptions for drugs of all types were filled in drugstores throughout the United States at a retail cost of $3.9 Lillion. Psychotropic drugs, as previously classified, made up about 17 percent of this total or 178 millia prescriptions at a consumer cost of $692 million. Forty percent of this total was accounted for by new prescriptions; 60 percent by refills. These figures for psychotropic drugs do not include those preparations which are mixtures of a psychotropic drug plus a non-psychotropic drug such as an antispasmodic agent, or a coronary vasodilating agent. If these combinations were added, the percentage accounted for by psychotropic drugs might rise to almost 25 percer.t of all prescriptions. Parenthetically, I might add that at this point we are not considering drugs sold over the counter (OTC) for the same indications as prescription psychotropic agents. We will return to these OTC preparations later.

Chart 2 shows the percentage of all psychotropic prescriptions filled in U.S. drugstores attributable to each of the major drug classes in the year 1967. The left bar in each case refers to the percentage of all new prescriptions accounted for by the class and the right bar shows the percent of new and refill prescriptions for the class. In that year there were 54.1 new prescriptions for psychotropic drugs filled for every 100 of adult population. The analogous figure for total psychotropic drug prescriptions, both new and refill, was 133.1. It should be pointed out that these acquisitions are obviously not equally distributed per person. From this chart it is clear that the minor tranquilizers and hypnotic drugs are the classes acquired most frequently.

'In this and subsequent charts and analyses prochlorperazine is not included in the major tranquilizer class since it is mainly prescribed for treatment of gastrointestinal dysfunction.

Let us now turn our attention to trends in drug acquisitions over the past 10 years.

Between 1958 and 1967 the number of new psychotropic drug prescriptions filled in U.S. drugstores rose from 42.7 to 70.6 million, an increase of 65 percent. During that same period, new prescriptions for all other drugs increased by 35 percent. However, it should be pointed out that a marked increase in new psychotropic drug prescriptions observable in 1966 is largely artifactual due to the passage of the Drug Abuse Control Amendments of 1965. These amendments set limitations on the number of refills for sedative, stimulant, and hypnotic drugs and this resulted in a sharp increase in new prescriptions.

From 1958 to 1965, in the 8-year period preceding the legislation, the rate of increase for new psychotropic drug prescriptions was 31 percent as opposed to 21 percent for all other drugs.

When trends for new psychotropic drug prescriptions are broken down by major drug class, it becomes apparent that the large overall increase (31 percent) that occurred between 1958 and 1965 is mainly attributable to minor tranquilizers (Chart 3). By 1967, the last year on which we have complete data, the number of new prescriptions for minor tranquilizers filled in U.S. drugstores had risen to 20.4 million. From 1958 to 1965, the 8-year period preceding enforcement of the drug abuse legislation, new prescrip tions for minor tranquilizers were advancing at the expense of the sedatives, mainly the barbiturates.

Because of the passage of the Drug Abuse Control Amendments of 1965, current trends for psychotropic drugs are better represented by the combined total for new and refill prescriptions. Between 1964 and 1967, the years for which we have data available, the total number of psychotropic prescriptions filled increased by 16 percent, from 149.1 to 173.6 million, while those for all other drugs rose by 26 percent. Thus, in recent years, prescriptions for psychotropic drugs have advanced at a slower pace than for all other drugs.

Growth rates for the individual classes of psychotropic drugs were also different between 1964 and 1967. In terms of new and refill prescriptions, minor tranquilizers have shown the greatest rise, from a total of 45.1 million in 1964 to 59.7 million in 1967 (Chart 4). Total prescriptions for antidepressants also rose sharply from 9.4 to 14.8 million, but their per centage of all psychotropic drug prescriptions remains small. The total number of acquisitions for the stimu lant and sedative classes has actually declined while major tranquilizers have remained relatively stable.

PERCENT

Hypnotics have shown a small increase in total acquisitions over these years.

Let us now turn our attention from the number of prescriptions filled to estimates of the actual number of adults (over 18 years of age) who have used psychotropic drugs in the United States. Information of this type is mainly available from probability-based survey studies in the general population. In one such study, performed in October 1967 by the Social Research Group of the George Washington University, respondents were asked the following:

Here are three questions about the types of pills that people use. For each of the three types of pills listed below, circle bow recently you have used that type.

CLASS

(a) Pills that help you sleep at night, like Sleep-Eze, phenobarbital, and the like;

(b) Pills to calm you down and keep you from getting nervous and upset-pills that often are called tranquilizers, like Equanil, Compoz, and the like;

(c) Pills that pep you up, help you stay awake, make you more alert and less tired, that help you lose weightpills that are often called stimulants, like Dexedrine, Dexamyl, No-Doz, Preludin, and the like.

Results of this national survey indicate that approximately one out of four adults have taken a psychotropic agent in the past 12 months and about one out of two have taken a psychotrope at some time in their lives. Similar surveys performed in 1967, both national and regional, have yielded almost

identical results. It is important to point out that the results of this survey include the use of over-thecounter (OTC) preparations as well as prescription psychotropes.

In evaluating figures for psychotropic drug usage in the general population, both prescription and overthe-counter, it is important to make a distinction between use of a drug, at one time or another, and fairly regular or frequent use. Data collected in a recent statewide survey in California indicated that 51 percent of the adults had used a tranquilizer, sedative, or stimulant-either a prescription or over-thecounter drug-at some time in their lives, but only 17 percent had done so frequently. In a more detailed study of 1,104 respondents in San Francisco, investigators from the Family Research Center of the Langley-Porter Neuropsychiatric Institute found that 54 percent of those who had used a prescription psychotrope at any time had done so only on an irregular or occasional basis or for periods of less than 1 month. At the other extreme, only 21 percent of the drug users reported regular daily use of a prescription drug for a period in excess of 5 months. Ninety

percent of those reporting use of over-the-counter psychotropic agents had either used them on only a few occasions or a number of occasions of short duration.

During the coming year a much more comprehensive national survey than any previously carried out will be undertaken by the Social Research Group of George Washington University with NIMH grant support to pinpoint in detail the extent and character of psychotropic drug use in the United States.

So much for the extent of psychotropic drug use. Now let us try to answer some of the more detailed critical questions posed earlier.

To Whom Are Psychotropic Drugs Prescribed?

This question has as many answers as the ways in which it is possible to characterize people. Today we will only talk about two of the more important characteristics related to psychotropic drug usage: namely, age and sex.

The large bulk of psychotropic drug prescribing occurs in the over-20 age group, principally for ages 40 to 59. Further, it is clear that stimulant drugs

42-121 O 70 pt. 1 17

NO. OF RX (IN MILLIONS)

are used much more extensively during young adulthood while the sedatives and hypnotics are most fir quently used in advanced ages. Use of minor tranquilizers and antidepressants is greatest in the age range 40 to 59. These data coincide with clinical knowledge that somatic disorders with stress components such as cardiovascular and gastrointestinal disorders, which are frequently treated with sedative drugs, occur in later life as do general problems of insomnia. The use of stimulants at an earlier age is strongly related to their use as appetite suppressants and anti-obesity agents.

Shifting our attention now to the sex distribution, females receive a much higher proportion of psycho

1967

tropic drugs than do males. On an overall basis they account for approximately 67 percent of all psychotropic drug usage, whereas on non-psychotropic drugs they account for 60 percent. Exactly why this differential exists is not clear and it certainly deserves closer study. It is interesting to note that stimulants and antidepressants are overwhelmingly "female drugs" and account for 82 and 74 percent of the use, respectively. Cross-tabulation of the age and sex variables indicates that with increasing age the male-female imbalance in receipt of psychotropic drugs tends to diminish.