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Historical Article   |    
The New Drugs (Chlorpromazine & Reserpine): Administrative Aspects
Addison M. Duval, M.D.; Douglas Goldman, M.D.
Psychiatric Services 2000; doi: 10.1176/appi.ps.51.3.327
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Editor's Note: The article on the new drugs reprinted below appeared in the February 1956 issue of Mental Hospitals. It is based on a discussion held during the Seventh Mental Hospital Institute in October 1955 in Washington, D.C. Chlorpromazine and reserpine had been available in the United States less than two years when the institute participants met to discuss how their hospitals were coping with the demands of the new treatments. In a commentary and analysis beginning on page 333, Robert Cancro, M.D., considers the broader impact of the introduction of neuroleptics and examines the concerns of the 1956 institute participants in the context of today.

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Our task this morning is to exchange information about the effects of the use of the "new drugs"—chlorpromazine and reserpine have been the most effective so far—for relatively large numbers of patients in large hospitals. A larger proportion of patients are being treated with them than we have so far been able to treat by other means. This is something which we have all encountered in our daily work with patients, and it seems as if not only the whole service, but the whole hospital has to be reorganized.

First of all we need a new kind of doctor in a psychiatric hospital—one who is not afraid of medicine; who is not alarmed by seeing an eruption which is the result of medication, but who can handle it properly; one who is not afraid if Parkinsonism occurs from either reserpine or chlorpromazine, but who will evaluate it as an index of the activity of the drug, and understand how to control it. Such problems require a new kind of attitude in addition to the psychiatric point of view, and this new attitude we might perhaps call a medical or pharmacologic understanding of what is going on.

This new kind of understanding cannot be confined to physicians. The nursing service also faces a huge new responsibility, because instead of looking after a couple of hundred patients receiving somatic therapy, it is now caring for thousands. How can 20 nurses supervise this kind of nursing? How can they even supervise the attendants?

The administrative aspects of the use of the new drugs may for convenience be divided essentially into the clinical administrative and the business administrative points of view.

Clinically, in addition to educating more medically and pharmacologically sophisticated physicians and nurses, we have to consider how many patients and what kind of patients should be treated by the new drugs because they are likely to benefit. What proportion of our patients can we treat? Can we give 100 patients one pill a day with only two attendants working on a ward? And is it possible to extend this treatment to the night shift with only one man on?

What effect does it have on the ward and on the hospital when many patients suddenly improve as a result of the drugs? A patient who has been in restraint for two or three years continuously, only out for the legal number of minutes per day under very close supervision, does not need restraint any more, and yet he is not a well individual. He needs a great deal of extra attention from the occupational therapy department, from the rehabilitation service, possibly from teachers and other people who can reeducate him into useful channels. Vocational rehabilitation may come into existence in many hospitals for almost the first time; the problems of social service in arranging for the patient to leave the hospital have to be considered. Then multiply this patient by hundreds or thousands. The nursing service, the rehabilitation services, the activities personnel and social service face a monumental task—a task to which they have not been accustomed.

Moving to the business administrative problems, we are all aware there is a huge rumble to be heard concerning the budgetary aspects. An ordinary, modest drug budget for a state hospital of say 3,000 patients is suddenly increased from its normal $15,000 a year to twenty times that figure! Instead of giving drugs to two or three hundred patients in small doses, we find ourselves giving massive dosages to one thousand or fifteen hundred; we would like to expand it to two thousand or more because we feel they would benefit. Yet at the same time we are asking money for additional staff.

How can we justify it? At our hospital, for instance, the number of patients in residence on July 1, 1955 was 80 less than on the previous July 1st. There is no other explanation except the effect of this increased treatment.

Another hint was given me by our Social Service Department recently. "There is something very curious going on," they told me. "Like every other hospital we have had patients coming back who have been out on convalescent leave or even on full discharge. Yet in the first eight months of the use of this medication, 93 patients went on convalescent status who had been treated by chlorpromazine or reserpine and whose medication was continued while on parole. Of these, six have returned to the hospital. During the same period 137 patients were on convalescent leave without the benefit of this outpatient drug therapy, and of this number 57 have returned."

This means that instead of coming back into the hospital the patient is given medication as an outpatient, is supervised once a week, then every other week, then once a month and finally every three months like any other patient on convalescent status. This reflects in the per capita daily and yearly cost.

According to some figures I have, using the most expensive kind of drug treatment, the lowest figure for treating a patient with chlorpromazine would be $12.24 a month—for 800 milligrams a day. If reserpine works the figure would be about $9.50 or $10. This is very much cheaper than even the lowest per capita cost, and if you treated a man as an outpatient for a year it would be cheaper than keeping him in a hospital.

The decrease in destruction of the physical plant, of soiling sheets and so on is more difficult to express in dollars and cents, but it could be done. Then the decrease in restraints—in our hospital restraints dropped from an average 14 and 15 a day to less than one a day during the last three or four months—cuts the cost of supervision, destruction of clothes, windows, benches, and so on.

I will now open this subject for discussion, and we will try to teach one another as much as possible.

Participitants:Freeman H. Adams, M.D., Calif.; Anthony K. Busch, M.D., Mo.; Charles K. Bush, M.D., D.C.; Philip N. Brown, M.D., Mich.; M. D. Campbell, M.D., Wash.; George W. Davis, M.D., La.; Mr. Mike Gorman, D. C.; Walter M. Gysin, M.D., Ky.; Daniel Haffron, M.D., Ill.; Franz X. Hasselbacher, M.D., Conn.; John R. Howitt, M.D., Ont., Canada; Granville L. Jones, M.D., Va.; Daniel Lieberman, M.D., Calif.; Rev. Moody A. Nicholson, Okla.; Arthur P. Noyes, M.D., Pa.; Miss Elsie C. Ogilvie, R.N., D.C.; Benjamin Pollack, M.D., N.Y.; Mrs. R. R. Tamargo, N.Y.; Robert R. Yoder, M.D., Mich.

Early in the discussion, questions were raised about dosages, selection of patients, possible risks, side effects and other clinical matters. In his capacity as internist, Dr. Goldman undertook to pass on his experience in these areas. The question of the maximum dose has been investigated in a number of places, one of the most important studies being conducted by Dr. Vernon K. Wright of Houston, at the Baylor Medical Center, who has given doses up to 4,000 and 5,000 milligrams a day. Certain patients do require doses in that range, although there is a greater tendency to produce organic confusion with large doses. At Longview, the maximum dose used is about 2,000 milligrams, and if larger, patients are put into the medical and surgical wards for closer and more continuous observation. Dr. Campbell of Washington spoke of a patient who received 3,000 milligrams a day and became tractable, but did not lose her delusions. She reverted on a lesser dose.

Reducing the frequency of doses, it was suggested, might solve some of the problems of ward administration. Dr. Pollack said that in long term cases, with small dosages, one dose a day was sufficient, but for larger amounts, twice a day was necessary. Dr. Gysin had tried twice a day doses of chlorpromazine to lighten the load of the nurses, but the patients did not do so well, and they reverted to a thrice daily dose. With reserpine, said Dr. Goldman, since there is a cumulative effect, medication once or twice a day is frequently quite therapeutically effective.

Dr. Jones of Virginia raised the question of side effects. He had a patient with marked agranulocytosis. Although it occurs rarely, should every patient taking the drug have a blood count every week? This would raise quite an administrative problem.

Dr. Goldman said that agranulocytosis occurs only with chlorpromazine. It occurred in four of his patients; one who had had a lymphosarcoma died. A study to be published in the October issue of the Archives of Internal Medicine outlines the kind of treatment to be used. It consists of intensive antibiotic therapy to prevent the infections to which patients with agranulocytosis are subject, and the use of ACTH in fairly large doses to stimulate bone marrow. With this treatment it is not such a threatening condition, although it is important to recognize it early. This emphasizes the need for doctors who are more medically oriented than many psychiatrists are at the present time. Dr. Goldman said he has found that this complication was practically limited to women, but Dr. Jones said that his patient was a man.

Dr. Brown said that he had two cases of agranulocytosis, both of whom died. Both were women, one 62 and the other about 57. The earliest symptoms were glossy throat, fever and lassitude; they were given massive blood transfusions, and antibiotics. They were not however given ACTH or cortisone.

Dr. Goldman said that in all illnesses such as pernicious anemia, agranulocytosis, and so on, blood transfusions suppress bone marrow activity. The condition apparently occurs only in patients who are getting at least 40 milligrams a day. He does not do blood counts, although he does watch his patients' closely during the first six weeks, particularly the women, and all other patients on fairly large doses.

A question was asked about the period of sleepiness which follows with both chlorpromazine and reserpine. Dr. Goldman said he considered this of no importance. He thinks it will still be a number of years before we have learned the very best procedure for handling patients after drug treatment. We are, however, in the process of developing this knowledge. He spoke of the other side effects to be expected from the use of the new drugs, of which Parkinsonism was the most serious. If this was carefully managed, however, it should not be too difficult. Reserpine can produce certain cardiovascular effects, but any reasonably competent clinician can handle these by adjusting dosages and giving other drugs. The agranulocytosis from chlorpromazine was found predominantly in middle-aged women; they have found no cases among children or patients over seventy. This latter might be because old people have been given lesser doses of this fairly potent drug. They had been given up to 900 milligrams a day of Frenquel, however, with no appreciable side effects.

Dr. Haffron asked whether chlorpromazine could be put up in spansules for the smaller maintenance doses of 50 to 150 milligrams a day. This would help solve the problem of dispensing the medication b.i.d. or t.i.d. Dr. Goldman said he thought that the biggest dose to be put out in a spansule would be 100 milligrams. It was not yet available, be thought, but was under consideration.

The fact that many patients threw away their pills instead of swallowing them was mentioned by several discussants. This would introduce a variable into the results, if you could not be sure who got the medication. It was said that this difficulty could be partially solved by enthusiastic and conscientious ward personnel. Dr. Haffron said that possibly others beside himself had had the unhappy experience of having a patient, after ward personnel had reported medication actually placed in his mouth, accumulate an almost lethal dose of a barbiturate and later take it at one gulp.

He also raised the question of the selection of patients, asking if we had yet reached the stage of being able to apply reliable criteria. He recalled that initially metrazol had been used only for schizophrenics, but later it developed that the indications were better in a depression than in schizophrenia. Many hospital physicians have had the experience of being pressured by relatives to use chlorpromazine where it did not seem to be indicated. To hold off relatives, he would say "If you will buy it, we will give it," being sure that they would not do so. But they always obtained the money somehow, and so it was used on passive, withdrawn schizophrenics where presumably it was not indicated. Some rather startling results occurred.

The drug is certainly not a panacea for all mental illness, said Dr. Pollack. Our expectations as to its effects vary according to the type of patient. Many physicians in private practice say these drugs are just a flash in the pan, yet when they see the results obtained in a hospital with carefully selected patients, they want to use them indiscriminately on their own patients.

Dr. Lieberman said that we should be cautious in ascribing all dramatic improvements to the use of the tranquilizing drugs alone. Many unknown factors, such as changes in attitude on the part of staff members, undoubtedly enter in. At Agnews State Hospital a control group was established and nobody treating the patients knew who the controls were. The study showed great improvement in both groups—those who had received chlorpromazine and those who had received placeboes. After the experiment was completed various clinicians, psychiatrists and psychologists endeavored to name those patients who had been on chlorpromazine. They were 58% right.

In Illinois a small double-blind study was also carried out on a small group of patients. The final conclusions cannot yet be drawn, but tentative conclusions indicate that it is quite possible to reduce the amount of chlorpromazine and reserpine and still obtain the same therapeutic results. The use of tranquilizing drugs for so many patients in so many hospitals leads to the need for better teaching of the basic therapeutic techniques so that everybody can participate in the program, whether with a simple or an advanced skill. The enthusiasm of the employees should be utilized and channelled into activities which are helpful to the patients. Not only the relatives get hopeful for the patients' recovery (and incidentally more people are coming into the hospital, said Dr. Pollack, because they are beginning to think of it as a medical instead of a custodial institution), but certainly the nurses and attendants will feel that they are accomplishing something. They are therapists—they are helping the patient. They are not just cleaning, feeding and so on. Miss Ogilvie said that it pointed up the need for more qualified nurses in the hospitals, if only because of the need for more in-service education for the non-professional people who are working on the wards where the new drugs are being given. This can only be done as it should be done under good supervision by nurses working in the team approach and with consistent teaching of the non-professional personnel. Neither nurses nor attendants must be turned into pill pushers who do nothing else but give medicine to the patients. These nurses can watch for the complications, especially acute appendicitis, bowel obstruction and so on, which may be masked by the use of the drugs. Some patients on chlorpromazine become very constipated. There are more fecal impactions than before; in one case, the bowel was perforated by giving an enema. This was not attributable directly to the drug, of course, but in a sense it was almost a direct result of its use. We must again improve our medical knowledge, from the doctors and nurses down to the attendants.

Dr. Hasselbacher raised the question of chronic schizophrenics who had not held or maintained their improvement, and relapsed very quickly when taken off the drug. What about sending such patients home? Should they go with prescriptions to take the drug at home under the supervision of a clinic or their local physician, or should we endeavor to have patients drug-free by the time they leave the hospital? If we know a patient to be assaultive without the medication, but fairly docile and acceptable at home under the medication, we must ask if he will continue to take it once he leaves the hospital.

Dr. Goldman said he thought the best answer was to continue treatment indefinitely just as you would continue insulin for a diabetic or Vitamin B12 or liver extract for pernicious anemia, anti-convulsants in epilepsy and so on. In sending patients home we should be careful to try to develop judgment as to how soon it is safe to discontinue and how much medication must be continued.

Dr. Pollack said that at present they have 250 patients being treated with drugs outside the hospital, most of whom had been inpatients. Some had applied for voluntary admission, but it was felt they could be better treated at home. Others were patients who had not been treated with the drugs in the hospital, but who after discharge had had symptoms of relapse and so were put on the drug. His normal return rate from convalescent care is between 30 and 35% without treatment; of the treated group, only 5% of the first 150 that he analyzed had returned. Only 7% of another group of 250 have returned, and this shows that there is a marked advantage in the treatment of patients after they leave. These patients may have to be treated forever, but this is a small price to pay for keeping them well and out of the hospital.

Dr. O'Donnell said it was extraordinary how one was always asked the question "How many patients are you getting out of the hospital?" Yet we all know that in all types of disease there are cases which will remain chronic in spite of everything we do. All the stress is put on how many patients may go out and very little consideration is given to how much comfort can be given to those who will never get well; the budget people never seem to be interested in whether or not the new drugs or the shock treatment will make life more pleasant and more livable for those patients who will have to remain in the hospital for the rest of their days.

Dr. Gysin said that every possible means should be used to get money for this new program; it would even be justifiable to stop other valuable programs and projects if you must to get over the hump, so that every patient who could benefit can continue to receive medication.

Dr. Goldman agreed that our enthusiasm was based on pretty objective concepts. He believes that the new drugs are as big or even a bigger advance than insulin or electric shock. Yet those people who were horrified at electroshock are now unwilling to give it up to use drugs!

Dr. Adams asked whether, since the general feeling is that there is ultimately going to be a reduction in hospital population, anyone has attempted to establish a base line from which the law of diminishing returns might operate to our disadvantage? In one sense, he said, we are talking out of both sides of our mouth. We want more money; we want more capital outlay; we want more staff—but we expect a reduced population.

Have we any experience to enable us to say how far we can hope to reduce the hospital population? Dr. Goldman said that answering that question would be essentially pitting human beings versus dollars. It is not too much to spend millions of dollars to save human lives and to make human lives more effective, when we already spend billions for the potential capacity to kill. However, the practical answer is something like this: for five or ten years we are not going to change the fundamental quantitative aspects of the problem much, because it will take that long to develop enough clinical understanding and experience of the usefulness and the nature of these drugs and their reactions and all the things that go with them. This means that we will need rehabilitation, social service and activities in increased measure—everything we know of that can be added to the drugs to make them effective. We do not know what will happen when we are no longer treating psychotics with the residual of ten, fifteen or twenty years hospitalization. Nor has any legislator, any Governor or anyone else a right to ask this question, because the real problem is that we do not have the right to put dollars against human beings.

Dr. Bush pointed out that the main theme of this [the seventh Mental Hospital] Institute was the freedom of patients. Certainly the use of these drugs has enhanced this program of freedom. We need both drugs and personnel to get patients out of the hospital more quickly; consequently, while the cost per day may increase, the cost per patient illness will decrease. This is certainly true with the use of the drugs. Therefore, more money for personnel and more money for drugs will ultimately result in a saving to the taxpayer.

There are some practical aspects regarding the architectural designs of new buildings which will certainly result from the use of these drugs and of other drugs not yet discovered if they continue to prove out as we think they will, he continued. There will be need for fewer detention rooms—indeed the need for any at all may be practically eliminated. There will be need for more activity rooms, more recreational and occupational therapy facilities; there will be need for less areas for electroshock and for more outpatient and day care facilities.

Most people believe that psychotherapy must be continued with the use of the tranquilizing drugs, said Dr. Campbell. However, with a very limited staff, he sends out a great number of patients who have not had any opportunity to experience psychotherapy and they seem to get along all right. Dr. Goldman agreed that it was difficult to evaluate psychotherapy, or any other kind of readaptation work, which may be a better general term. Patients who have been admitted only recently have not lost all the elements of social and industrial adaptation. Once they get well they can quickly pick up the threads again. The hole that was left in society by extracting them and putting them into the hospital has not yet been overgrown by weeds or filled in. But when patients have been in the hospital for five, ten or fifteen years, and yet reach the point where they can be rehabilitated, it is going to take a great deal of activity by a great many people to make the patient himself capable of readapting usefully to society.

Psychotherapy is not the formal matter of what happens between the doctor and patient in a face to face relationship; it includes much that is indefinable and will be required more by those who have lost their relationship to society than by those whose illness is of more recent origin. With such long term patients, we must first treat the illness and then rehabilitate the patient. That is the technique which is now in the process of development.

Dr. Goldman called upon Mr. Mike Gorman to speak briefly on the question of the budget in relation to the new drugs.

Mr. Gorman said it wasn't difficult to go to a Legislature which was already cognizant of the public pressure for these new drugs. They would certainly ask "How many people will you get out? Will you reduce your patient population? Can you cut your capital construction?" These questions were academic and fairly nonpsychiatric.

What is needed is a real, solid, statistical and financial evaluation, instead of the usual testimonial. It is right and incumbent on a public body which is spending public money to ask these questions, and they have a right to clear answers, not obfuscations and controversies. They are not simple questions to answer. We cannot say tomorrow that some such answers can be given. But we must try to establish norms and standards, to show that we realize our responsibility to the taxpayer. We cannot make false promises. We cannot say that we will reduce our population by one thousand or some such figure. But we can say that we hope to do this within five or ten years, and that here is our broad experience so far to support these hopes.

This year we have managed to persuade the Senate to set up a special chemotherapeutic panel through the National Institute of Mental Health. This panel is to select ten or twelve of the larger hospitals and establish controls and standards—tough statistical and biostatistical standards. This work is to go on for a year or two, and will be in a sense an epidemiological study, in depth, rather like the studies of Malzberg in New York State—the kind of thing that you can look at and not groan after the first two pages. Since 96% of our burden is a tax one, and we have to meet annually with budget directors, those people have a right to be a little surly if we cannot give them the figures they justly request.

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