Lapas attēli
PDF
ePub

Rather than solving the difficult problems of the hospital treatment of the mentally ill, the availability of a drug such as this introduces grave problems for the conscientious hospital administrator, psychiatrist, and nurse. We believe it will be found that while the burdens of caring for the disturbed are lessened by reserpine, the challenge of providing appropriate additional psychiatric treatment for those no longer disturbed will tax all of our ingenuity, skill, and resources.

It is with some of these problems that the remainder of this paper will deal. By the very nature of the state of our scientific knowledge regarding the etiology of the mental illnesses and the various therapies used to treat them, these problems will have to be dealt with primarily as questions to which answers must be found.

Problems in Widespread Use of Tranquilizing Drugs

Extent of Use

Much has been written about the widespread use of the tranquilizing drugs. However, I know of no study that permits estimation of the proportion of persons who are on these drugs in the various age, sex, and diagnostic groups in mental hospitals, among the general population under treatment in outpatient psychiatric clinics or under the care of private psychiatrists, general practitioners, pediatricians, internists, and obstetricians. It would seem basic to our inquiry to find out how widespread is the use of the drugs, in what branches of medicine they are being used, on whom, and for what purpose.

Safety

Basic questions on safety of the tranquilizing drugs are:

How safe are these agents for the patient? How toxic are these drugs?

What are their immediate as well as their long-range effects?

How are these effects related to dosage?

How should dosage be modified in relation to the various characteristics of patients, such as age, sex, race, type of psychiatric disorder, duration of illness, general physical state of the patient?

How long should patients be kept on these drugs?

Because of their tranquilizing properties, it is important also to know about the psychological effects of the drugs-for example, production of depressive reaction with re

serpine and the characteristics of the individuals in whom these effects are most likely

to occur.

Chlorpromazine

The large variety of toxic effects produced by chlorpromazine in man are well known. Among these are severe hypotension, dermatitis, parkinsonism, jaundice, and agranulocytosis, to name only a few. Because of the way many of the results are reported, it is difficult to compare incidence of complications between studies by age, sex, type of disorder, and so on. However, Freyhan's data on the Delaware State Hospital population (9) give some indication of the frequency of the various complications reported in mental hospital patients. In 237 patients in a variety of diagnostic categories, 9.3 percent developed parkinsonism; 14.3 percent, allergic dermatitis; 0.4 percent, diarrhea; 4.2 percent, constipation; 3.0 percent, jaundice; 12.7 percent, "toxic" reactions; and 2.2 percent, miscellaneous other complications. A problem for the clinicians is determination of the implication of these complications for the selection of patients for treatment with these drugs and the indications for varying dosages and termination of treatment.

Two points merit discussion. The first is that the dosages of chlorpromazine used in man impinge closely upon dosages that have been found to be lethal in animals. The approximate 14-day LD-50 in rats has been reported to be 25 mg./kg. for intravenous administration (10) and 492 mg./kg. for oral administration

(11). With respect to this observation, Evarts,1 in a recent memorandum, made the following comment:

Toxic effects with chlorpromazine at therapeutic dosages in man are numerous, and occur with great frequency. Of interest in this respect is the fact that the dosages used in man impinge closely upon doses that have been found to be lethal in animals. It is not uncommon for human subjects to receive 50 mg./kg. daily for several weeks, either by intramuscular or oral administration, The figures quoted above for the 14day LD-50 in rats indicate that the 50 mg./kg. used in man is between the intravenous LD-50 in rats (25 mg./kg.) and the oral LD-50 in rats (492 mg./kg.). The fact that the human dosage is in this high range may explain the common appearance of numerous toxic manifestations.

To be sure, there are species differences in tolerance to various drugs and in the mortality resulting from them. However, Evarts' comment does raise the question of whether the tranquilizing drugs may have an adverse effect on the expectation of life of persons treated with them.

The second point is that there is a tendency to continue use of chlorpromazine despite the appearance of a complication, such as parkinsonism. For example, several participants in the recent symposium on chlorpromazine and mental health (2) reported that patients who developed basal ganglion symptoms seemed to show "more improvement" and indicated that medication with chlorpromazine was continued in spite of the development of this complication. Goldman (2, p. 93) reported:

... pushing the drug to the point of achieving parkinsonism response and, then treating the parkinsonism with another drug. which relieves the parkinsonism totally or almost totally.

Ayd (2, p. 56) stated he had been debating whether or not he "should deliberately produce basal ganglion symptoms in patients with the object of increasing the improvement rate." These comments raise the question as to whether the appearance of the parkinsonianlike syndrome is a good prognostic indicator and as to whether the drug should be pushed despite the development of this side effect.

1 Unpublished memorandum on psychiatric use of chlorpromazine and reserpine from Edward V. Evarts, M.D., acting chief, Laboratory of Clinical Sciences, National Institute of Mental Health, Bethesda 14, Md.

Reserpine

Reserpine is also known to produce a variety of side effects, such as parkinsonian symptoms, depressive reactions, confusion, loss of appetite, torpor, chilliness, tremulousness, nasal congestion, and diarrhea (1-3). Two of the important side effects are production of parkinsonian symptoms in psychotics and the occurrence of severe depressive reactions in patients on whom the drug has been used as an antihypertensive agent and in whom the primary focus of treatment was not for a psychiatric disorder.

With respect to parkinsonism, Kline and Stanley (12) state that their general attitude has been "to press treatment despite parkinsonian symptoms until the patient appears either on the road to recovery or gives evidence that a good response is unlikely." As indicated above with chlorpromazine, this practice needs further evaluation.

With respect to the development of depressive reactions, three papers in the October 29, 1955, issue of The Journal of the American Medical Association reported on depression, anxiety, and psychosis apparently produced by reserpine and other rauwolfia products in patients being treated for hypertensive vascular disease. Muller and associates (13) reported that 7 of 93 patients (7.5 percent) receiving rauwolfia for periods of 2 to 12 months developed a severe mental illness. Two of the 7 patients responded to reassurance and supportive therapy and 5 required electric shock therapy. Schroeder and Perry (14) reported the occurrence of psychotic behavior with agitated depression in 5 patients receiving reserpine (the total number treated was not mentioned).

Achor and associates (15) reported that emotional upsets developed in 10 of 58 patients (17 percent) during the course of their study, with 3 patients experiencing a "truly major depression." One of these required electroshock therapy, another was under psychiatric care for many months, and the third, who left town abruptly, was later discovered to have been hospitalized and under psychiatric care. These investigators also report that, in the treatment of 70 other hypertensive patients followed since January 1954, they encountered 15 patients (21 percent) with depressed states.

Of these, 1 committed suicide, 1 attempted suicide, 2 required electroconvulsive therapy, and 4, prolonged psychiatric management. The remaining 7 patients had milder manifestations but had to be taken off treatment with rauwolfia. Achor and his colleagues comment:

Because of the seriousness of this problem, nearly all patients with a depressive reaction have had psychiatric evaluation, and this problem is the subject of continuing investigation. We have been advised that all such patients had ample psychological background to render them susceptible to development of a depression. However this may be, it is our present belief that Rauwolfia serpentina increases the vulnerability of these susceptible persons to factors in their environment that may promote a depressive response. We believe that the seriousness and frequency of these reactions constitute a major contra-indication to the indiscriminate and unsupervised use of rauwolfia preparations in persons with essential hypertension. Since these drugs are quite useful in treating hypertension and since other side-effects attending their use are not serious, it would be most worthwhile if some means could be found to recognize, prior to beginning treatment, those patients who might become depressed. It is to be hoped that further study of this problem will shed light on how to avoid such distressing and disabling depressive reactions.

Thus, the fact that the use of rauwolfia products can produce such severe mental disorders with suicidal tendencies as a "side effect" in persons being treated for hypertensive heart disease, another major health problem, does pose a serious question. Furthermore, if these products are being prescribed as a sedative for a significant segment of the persons in the various age, sex, and occupational groups of our population, it is urgent that we learn more about other psychological effects of these drugs as well as their biological effects. For example:

Are many persons in the industrial population on these drugs? If so, how are their reaction times and learning abilities affected? Are such persons subjected to higher accident risks than persons not on these drugs?

ing the drugs will be more susceptible to attack of mental disorders or other types of diseases?

It would appear, therefore, that much more information is needed on the biological, physiological, and psychological effects of the tranquilizing drugs at various dosage levels when they are used to treat psychiatric disorders, hypertensive vascular disease, and other medical problems in the various age, sex, race, and occupational groups of the population. Because of the beneficial effects of these drugs, it is also worth exploring whether homologues can be synthesized which will not produce undesirable side effects.

[blocks in formation]

Is it safe to permit persons to drive automobiles while on these drugs?

[blocks in formation]

Are these drugs being used as a sedative for children? If so, how do the drugs affect "normal" psychological and emotional development of children? What effect do they have on learning processes, and so on?

Do these drugs produce any damage or cause changes either in the central nervous system or in other organ systems so that persons receiv

[blocks in formation]
[merged small][merged small][merged small][graphic][subsumed][subsumed][merged small][subsumed][subsumed][subsumed][merged small][subsumed][merged small][merged small][subsumed][merged small][merged small][merged small][merged small][subsumed][subsumed][merged small]

creates a serious economic problem for the patients themselves, their families, and society in general. The details of this problem have been discussed fully elsewhere (16-18). Some pertinent facts are summarized here.

In the United States, there are 226 State, 47 county, and 324 private hospitals for mental disease, as well as the 39 Veterans Administration neuropsychiatric hospitals. The distribution of these hospitals by average daily resident patient population during 1954 is given in table 1. The median population for the State hospitals is 2,043; for the county hospitals, 267; for the Veterans Administration neuropsychiatric hospitals, 1,343; and for the private hospitals, 30.

As of June 30, 1951, there were 584,000 patients, or 3.9 per 1,000 civilian population, resident in all hospitals for the prolonged care

1925

1930 1935 1940 1945 1950 1955

of the mentally ill in the United States. In a single year, the movement of patients in and out of these hospitals is considerable. For example, as of July 1, 1950, there were 671,000 patients on the books and in the following 12 months there were 266,000 admissions, making a total of over 937,000 patients under the care and supervision of mental hospitals during that year. Discharges in the same 12-month period number 192,000 and deaths, 48,000.

Between the years 1903 and 1951 the number of resident patients in these hospitals increased almost 4 times (from 150,000 to 584,000) whereas the general population only doubled. Thus, the number of patients per 1,000 population doubled, from 1.9 to 3.9 (fig. 1 and appendix table 1).

Figure 2 and appendix table 2 show the geographic differences in the United States in

the age-specific resident patient rates, that is, the proportion of the population in various age groups in a mental hospital as of the last decennial census in April 1950. The agespecific rates for resident patients increase quite rapidly with advancing age, from 34 per 100,000 population in the age group under 15 years to 1,726 per 100,000 in the age group 85 years and over. The rates are consistently higher in the northeastern section of the country, where they rise from a low of 72 per 100,000 population in the age group under 15 years to 1,150 per 100,000 in the age group 55-64 years to 2,282 per 100,000 in the age group 85 years and over.

Figure 3 and appendix table 3 show the first admission rates for patients admitted to State mental hospitals in the United States in the years 1933, 1940, and 1950. During 1950, the first admission rate to the State hospitals rose from a low of 2 per 100,000 for persons under

Figure 2. Number of resident patients per 100,000 civilian population in all mental hospitals, by age and regions of the United States, April 1, 1950.

NORTH EAST

NORTH CENTRAL SOUTH

[blocks in formation]
[blocks in formation]

WEST

1500

1000

500

-15 15- 25-35-45-55-65-75-85+ 24 34 44 54 64 74 84 AGE (IN YEARS)

SOURCE: U. S. Bureau of the Census: United States census of population: 1950, vol. IV, Special Reports, pt. 2, ch. C., Institutional population. Washington, D. C., U. S. Government Printing Office, 1953.

AGE (IN YEARS)

SOURCE: Patients in hospitals for mental disease, 1933. Issued by U. S. Bureau of the Census. Patients in mental institutions. Issued by U. S. Bureau of the Census, 1938-46; by U. S. National Institute of Mental Health, 1947-51.

15 years of age to 87 in the age group 35-44 years, leveled off to between 85 and 90 for persons 45-64 years, and then climbed rapidly to a high of 205 at ages 65 years and over. Between 1933 and 1950, these rates showed no striking variations for the age groups under 65 years. However, in the population 65 years of age and over, the rate per 100,000 increased from 157 in 1933 to 170 in 1940 to 205 in 1950.

Figure 4 and appendix table 4 show the agespecific first admission rates to State hospitals in 1950, by diagnosis. In the age range 15-49 years, schizophrenia and manic-depressive psychosis predominate. During the next decade of life, the involutional, syphilitic, and alcoholic psychoses attain considerable importance. In the sixties, the cerebral arteriosclerotic and senile psychoses assume prominence, and these

« iepriekšējāTurpināt »