-Caveat Lector-
http://www.erowid.org/pharms/chlorpromazine/chlorpromazine.shtml
BRAND NAMES Chlorpromazine; Thorazine
(manufacturer SmithKline Beecham)
http://www.mentalhealth.com/drugrs/f33-c01.html
http://ps.psychiatryonline.org/cgi/content/full/51/3/327?view=full&pmid=10686237
Psychiatr Serv 51:327-331, March 2000 © 2000 American Psychiatric
Association
Historical Article
The New Drugs (Chlorpromazine & Reserpine):
Administrative Aspects
Addison M. Duval, M.D., Washington, D.C. and Douglas Goldman, M.D.,
Ohio
Abstract
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.
Presentation
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.
Budgetary aspects
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.
Discussion
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.
Knowledge of effects developing
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.
Outpatient treatment
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.
Architectural plans affected
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.
> Daniel Foscarini wrote:
>
> I am currently updating a report on Thorazine. I am having
> problems
> tracking down the manufacturers of this drug, also known as:
>
> Thorazine, Ormazine, Thor-prom, Chloropromazine, and Largactil.
>
> Any links CTRL members could help me with on the subject
> (highlight
> natural alternatives) would be greatly.......... ummmmmm, worshipped.
> (yes,
> this report is starting to get to me.)
>
> I am also interested in any articals or info that relates to
> antipsychotics, that have been found NOT to help, but just mask the
> conditions.
>
> I will post a link to the report when done, if it is to big post
> completely.
>
> Dan Foscarini
> [EMAIL PROTECTED]
--
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