FOR RELEASE
AM'S FRIDAY, FEB. 17

A PROPOSAL FOR THE TECHNICAL EVALUATION OF PSYCHIATRIC DRUGS

 

TESTIMONY BEFORE
HOUSE APPROPRIATIONS SUBCOMMITTEE ON LABOR-H.E.W. HEARINGS
ON FISCAL 1957 BUDGET (REP. JOHN FOGARTY, CHAIRMAN)
10:00 A.M., THURSDAY, FEBRUARY 16, 1956
by
DR. NATHAN KLINE - Orangeburg, New York

Director of Research, Rockland State Hospital, New York.

Mr. Chairman and members of the Committee:

Pharmaceuticals capable of modifying thought, behavior and feeling, may ulti-
mately prove of equal or greater importance than the introduction of atomic power. In
the history of civilization man has demonstrated his capacity to control virtually every
aspect of the universe except himself. We are not yet near the point where pharma-
ceuticals will protect us from emotional infection and disease but the first steps have
been made to show that subtle alterations of the chemical structure of the body can, in
some cases, change violently assaultive psychotics to happy and productive individuals.
This is not hearsay evidence: at Rockland State Hospital we have treated some three
thousand patients and I have personally seen scores of these patients, once considered
"hopeless", return to the community and take up their lives. As indicated in one of
our recent publications, in one of our buildings for chronic patients less than 5% of
the 740 residents were discharged in the year prior to the start of the new drug
therapies. In the past year we have released 15%. Of the chronically ill so treated
approximately 5% recover who would probably not have done so otherwise. In the more
acute patients who have been ill a shorter length of time much higher percentages have

been discharged. Attached is a table illustrating this point (Table 1). Even among
-2-

those not recovering sufficiently to be discharged some three quarters have shown some
degree of improvement. Chronologically we are probably about where investigations
of radioactive phenomena were at the turn of the century.

Since the last ice age most of mankind's major disasters have been self-incur-
red. The assaults against peace and progress were triggered by paranoid, guilt rid-
den, anxiety laden, depressed or otherwise emotionally disturbed deviants with delusions
of grandeur or of world destruction. One can only conjecture what a future might be
like in which there were not demagogues and dictators motivated by fear or hate or
pathological ambition.

There were violent protests when anesthesia was introduced into surgery and
childbirth on the grounds that man ''was meant to suffer" but there are now very few
who would choose to return to such barbarities as were then necessary. Many of the
life-saving medical techniques would be impossible without anesthesia. The days of
woman, at least, are no longer three score years and ten since by reason of the anti-
biotics and other medical advances the average life span is approaching 75 years. The
Hoover Commission has pointed out, however, that there is little point in prolonging
life "if we are to end ingloriously with the senile psychoses."

In my private practice I have had a number of business executives incapacitated
by anxiety who were relieved by these medications. In a number of writers and artists
long arid periods of non-productivity were "broken'' with these treatments and in a
sizeable number of housewives, lawyers, accountants and others, disabling fears and
"psychosomatic" symptoms were sufficiently relieved to permit more effective psycho-
therapy.

Within the past two years many of the mental hospitals in the country have made
a long step toward becoming treatment centers completely unlike anything known in
the past. In a paper delivered before the Midwest Regional Research Conference of
the American Psychiatric Association earlier this year, we estimated that five percent
of the chronic schizophrenic patients in hospitals could be released if adequate applica-

tions of the pharmaceuticals then available were properly applied. The figures which
-3-

Dr. Brill, Assistant Commissioner of Mental Hygiene for the State of New York, will
subsequently present seems strongly to confirm this estimate.

The millions of dollars of direct saving to the taxpayer is as nothing compared
to the immeasurable saving in human suffering and social disruption which the illnesses
of such individuals entail. The application of these drugs has undoubtedly spared many
patients the need of being sent to a mental hospital. Knowing about the reported favor-
able results many patients are voluntarily seeking admission. The usefulness of these
medications are illustrated not only by their widespread use but by the fact that the
sale of barbiturates has been markedly reduced. Despite the fact that barbiturates in
psychiatric patients act primarily to dull the senses or provide sleep which anxiety and
worry prevent, there nevertheless has been manufactured about 600, 000 lbs. per year
in the United States. When one takes into account one pound provides approximately
5, 000 doses of medication, the sale of 3, 000 tons of this material means a total of 3
billion doses. By the reports of two manufacturers of barbiturate the sale in 1954 drop-
ped to about 82% or 83% of the 1953 figure and in 1955 the sale had dropped to below
60% of the 1953 base line. Both companies attributed this drop to the substitution of
more effective medications -- primarily reserpine and chlorpromazine.

Newer preparations are now being tested and as the drugs become safer and
more effective new and different applications become possible. An editor of one of
this Nation's best known publications suffered acutely in the high pressure conferences
to which his work subjected him. Not only was his efficiency reduced but his over-
reaction to his colleagues in turn reduced the effectiveness of some of the meetings.
He now finds that by taking a suitable amount of medication an hour or two before his
conferences that he no longer becomes upset and is able to function much more ef-
fectively. But we hasten to add that other private patients in similar situations donot
always respond with uniform success. We are still fumbling at the beginning of know-
ledge and what we do not know is much greater than what we do know.

Let me emphasize that although the pharmaceuticals presently available some-

times and in some cases do bring about improvement that our ignorance of the proper
~4-

applications of these medications, of how they work, and of what new ones may eventual-
ly be produced is still minute compared to what must yet be done. Our appearance
before this committee today is not only to bring to your awareness the hopeful develop-
ments in the field of mental health and mental disease. The Congress is in a position
to perform both an important and a necessary function by making it possible to imple-
ment a nation-wide study of how and where the drugs presently available can most ef-
fectively be applied, and also to provide a stimulus for research into new pharmaceu-
ticals and new methods of applications. Since I had the good fortune to introduce one
of these groups of drugs -- the Rauwolfia alkaloids, including reserpine, into the treat-
ment of psychiatric patients (so far as our Western civilization is concerned) I have
been consulted by any number of individuals and groups of individuals who saw a
potential usefulness for such drugs. Projects involving the treatment of drug addicts,
of juvenile delinquents, of alcoholics and a host of other of our social problems have
all shown promise. Our one great lack has been a definitive study on a nation-wide
basis and it is on this particular aspect of the problem that I would like to propose

that action should be taken.

On the attached sheet, with the help of Dr. Brill, I have outlined a project
which would fulfill this need. In a hospital such as Rockland State we have seen
graphically and dramatically what the drugs are capable of doing. In the attached
figures (Figs. 1, 2, 3) it is obvious that restraint, seclusions and camisoles have
been markedly reduced since the introductions of these new treatments. Since treat-
ment with the new drugs has been vigorously applied the disturbed wards are now
quiet, patients are no longer in restraints or camisoles, there are curtains at the
window, vases of flowers on the tables and recently when I was showing a visitor
through, patients were cutting out and sewing costumes for a ward party. Two years
ago to have brought a pair of scissors or any sharp instrument on the ward would have
been not only unwise but dangerous. Now they are something that is of therapeutic
help to the patient. We know that the calming effects of the drug are almost universal

wherever and whenever applied: The degree of effectiveness in getting patients well
-5-

enough to not only leave the hospitals but to remain useful members of the community
is something much more in dispute. It is particularly in this respect that the nation-
wide evaluation under a variety of settings is necessary to determine to whom and how
the drug should be used. The Congress has a history of having most effectively imple-
mented similar projects in respect to streptomycin and cortisone. In this area of even
greater economic and social importance it would therefore seem most appropriate to
request that a similar project be supported.

There is strong evidence that the excited disturbed patients do somewhat better
than the quiet ones and we know quite definitely that the shorter time a patient has been
hospitalized the better are his chances of discharge. We would propose that both
disturbed and non-disturbed (both acute and chronic) patients be investigated in five
different hospitals at various points throughout the country. For reasons explained in
the attached sheet we feel that only adults should be included in the present project and
they should be limited to schizophrenic psychoses and be between the ages of 20 and
45 years. The patient should be free of organic disorders and since the facilities in the
community are better for return of such patients, we believe they should be female. It
is estimated that six months will be required to assemble suitable personnel and that
another three months will be consumed in selecting the patients -- eight hundred in all,
who would be included in the investigation. Six months would be a minimum period for
treatment following which another three months would be needed to evaluate the degree
of improvement achieved. The acute and immediate use of the drugs could then be
estimated allowing an additional half year for statistical analysis and preparation of
report. This phase of the project would therefore occupy two years. There remains,
however, a continuing problem since it is of at least equal importance to know whether
the patients improving by means of these treatments are able to remain out of the
hospitals. It is, therefore, recommended that half of the patients be continued on
medication at the end of the six months treatment period and the other half either be
discontinued or placed on tablets which are identical with the original active prepara-

tions except that they contain none of the active drug. The patient should be evaluated
-6-

yearly (particularly those who are discharged from the hospital) to determine the long
term action of such preparations.

At the present time there appear to be only two drugs which have been widely
enough tested to justify inclusion under this project. These are reserpine (previously
referred to) and chlorpromazine which appears to produce an equal degree of improve-
ment - but not always in the same type of patient. The use of these two drugs in
combination would constitute a third method of treatment which it is necessary to test
and a fourth group of patients should be included in the above design to receive iden-
tical tablets which are pharmacologically and chemically known not to produce the same
effects. This last group, since they will not be receiving the therapeutic action of the
drugs, will act as a control to determine whether it is merely the administration of
any kind of a pill or the drugs themselves which are effective in making possible the
release of patients from the hospital. The acute patients in this group should receive
the best psychotherapy available (at least 3 times a week) so that they will be actively
treated but by a different method. In the project outlined the funds requested are not
so much for the purchase of the drugs but for the employment of the highly skilled
personnel necessary to carry out such a piece of investigation.

In addition to the million dollars requested for the overall nation-wide evalua-
tion it would be equally important that a like amount be set aside for the investigation
of new drugs and new applications of the drugs already available. Many of my col-
leagues are working at such projects but all of us are hampered to some degree by
inadequate funds for the careful evaluation of the effects of such medications.

Investment of money for this purpose is not only an investment in the present
since there will be immediate practical returns, but it is also making possible future

developments of probably even greater significance.
PRESENTED AT THE AMERICAN ACADEMY OF PSYCHOSOMATIC MEDICINE MEETING 1955

Duration

less than 1 year
1 to 3 years

3 to 5 years

more than 5 years

TABLE I

IMPROVEMENT OF DRUG TREATED PATIENTS
RELATIVE TO DURATION OF HOSPITALIZATION

Marked

64%
33%
25%
6 1/2%

Moderate

16%
25%
30%

31%

Slight

 

13%
26%
30%
44%

None No.

 

6%
16%
16%
19%

Relapse rate of approximately 1/3 from these figures

of Cases
67

141

126

366
PRESENTED AT THE AMFRICAN ACADEMY OF PSYCHOSOMATIC MEDICINE MEETING 1955

 

 

 

joo ° o- & °
rd e
o e
eo o
td eo
o
° NEW Drugs
*
.
e e .
So} 7 °. woe
° =
e
.
CAMISOLES
oO x tT t
(952 G53 1954 1 (55

FIG, I
PRESENTED AT THE AMERICAN ACADEMY OF PSYCHOSOMATIC MEDICINE MEETING 1955

joo

 

50%

 

 

ee — New Drugs
lo ~ ° ~ / e
, °. * t . °

eo ar ° pnd

¢
9
Seclusions
(152 | i963.) 95% | (55)

:
PRESENTED AT THE AMERICAN ACADEMY OF PSYCHOSOMATIC MEDICINE MEETING 1955

 

 

°
o ’
[00 J, {-2-e0———-———4 + + .
e e eee 9 @
NEW Drucés
50°] "oe. to. oe
RESTRAINTS
Oo — T T * =
G52 5 If §3 1954 \ 1955

FIG. 3
APPENDIX A

A PLAN AND A DETAILED BUDGET FOR AN EVALUATION OF THE NEW DRUGS

The table of organization would be as indicated in the scheme below. The
National Institute of Mental Health would appoint a director for the project whose
responsibility would be to see to the implementation of the proposal. It would be
necessary for him to have secretarial assistance and the use of a chief statistician
with suitable statistical assistance in setting up the project.

The director would select five hospitals encompassing a variety of social
and economic milieus. Ratings such as those provided in the NIMH report on psycho-
.surgery (edited by W. Overholser) might provide such a basis with one hospital being
drawn from each twenty percentile. It would be necessary that the hospitals be those
in which the drugs had not yet been extensively used or where doses had been so low
that to all effects and purposes they had not been tried at therapeutic levels. It
-would also be necessary that the records be adequate for clinical purposes. The
director would be responsible for contacting the appropriate state authorities and
obtaining their consent and cooperation in the project. At each of these hospitals, a
non-physician administrative assistant to the Director should be appointed from the
regular hospital staff and for the duration of the investigation be paid by the project.
He should be thoroughly familiar with the hospital's record-keeping system and it
would be his responsibility to undertake the preliminary screening of the records
and provide the list of patients who might be suitable for investigation. There also
should be appointed at the hospital a liaison medical officer who would be supported
by the project, who would review each of the patients to determine whether their
current status is such that they actually do meet the criteria. The criteria for in-

clusion are tentatively suggested as follows:
1. Females -- to make the group as homogeneous as possible. 2. Certified
patients -- this would reduce the likelihood of patients withdrawing from the project
after it has been started. 3. Functional psychoses -- these should be as nearly

classical cases of schizophrenic psychoses as can be obtained. 4. Age range should
be from twenty to forty-five years -- this will help avoid the problem of adolescence
or changes which occur with aging. 5. Free of organic disorders -- this would
eliminate the likelihood that the disease might be due to changes other than the basic
psychiatric disorder. 6. First admissions -- it is obviously difficult to estimate
the duration of illness before admission but in the acute cases particularly, care
should be taken to make certain that these are not patients who have been ill fora
long time and merely maintained at home.

Although in the final project there should be forty patients of the chronic
disturbed type, forty patients of the chronic non-disturbed type, forty of the acute
disturbed and forty of the acute non-disturbed in the preliminary screening at least
an additional fifty percent in each group should be provided so that replacements are
available if a patient must be discontinued for any reason whatsoever.

It is recommended that each group of forty patients be placed on one ward
so that there is continuity of similar environment and personnel. This would require
four separate wards and it is recommended that in order to have careful records
that the project provide to the hospital four nurses for each of the wards so that one
of them may be on duty at all times. In addition, a secretary would be necessary
for maintenance of records and a lab technician with necessary equipment to keep

check on possible side effects which require laboratory testing.
Once the basic patient group has been selected along with the fifty percent
replacement reservoir, a rating team composed of a principal psychiatrist with an
associate psychiatrist, a psychologist with an assistant and a social worker should
be brought in from outside the hospital. It is recommended that they be drawn from
the Department of Psychiatry at a nearby University Medical School but preferably
one not ordinarily servicing the hospital in any way. The function of the group is
to evaluate the psychiatric and psychological status of each patient. The emphasis
should be placed on the social worker to ascertain as far as possible that patients
taken into the project would have places in the community if their improvement were
sufficient to warrant it.

After evaluation of the patients in respect to their current status and proba-
ble prognosis, the patients should be treated for a period of six months with adequate
doses of the drugs. In the case of the acute patients it is felt necessary for patients
not receiving active drugs to be given intensive psychotherapy (a minimum of three
hours per week for the period during which other patients are placed on active drugs).
It is believed valuable to give these patients identical pharmaceuticals except that
they would be non-active. The patients placed on drug therapy should be handled in
the ordinary hospital manner and not given the benefit of additional psychotherapy.
The choice of psychotherapist would rest with the Director of the project and the
Superintendent of the hospital or the Commissioner of Mental Hygiene of the State.

No patient should be considered a failure unless he has been treated for
three months with a minimum of four hundred milligrams of chlorpromazine daily
until the patients had improved sufficiently to be considered for discharge or until

the end of the project treatment phase. With reserpine three milligrams orally
and five to ten milligrams intramuscularly for at least the first six weeks anda
maintenance dose of three milligrams until discharge or until improvement was
such that it was felt medically advisable to reduce the dosage. On combined reser-
pine-chlorpromazine treatment two milligrams orally and fifty to one hundred
milligrams chlorpromazine would be considered minimal dosage unless there were
strong medical indications otherwise. At the end of the six months treatment period
the group would again be evaluated by the original rating team. Those patients who
had improved sufficiently to have left the hospital should be recalled for the time
during which the ratings occurred. Treatment should be continued during the
evaluation period as medically indicated.

Another six months would be required to statistically analyze and prepare
a report on this project. This would provide definitive information on the use of
the drugs in the intensive phase of treatment. It is believed that half of the patients
able to leave the hospital should be continued on maintenance doses of the drugs
they are receiving whereas the other half should be discontinued. Selection should
be on a random basis. In the event of relapse patient should be retreated and dis-
charged on maintenance dose if improvement occurs a second time. Itis suggested
that the forty patients in each of these sub-groups be first selected and then ran-
domized into the four sub-groups in order to avoid any systematic bias. In the same
manner five of each of the ten patients in each cell should be randomly selected be-
fore the project begins to determine which of them will be continued on maintenance

doses subsequently. Replacements, as indicated above, should be available.
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Ho spital E

——

 

USPHS
Director Advisory
of Study
Project Group
Statistical Chief
3 Assistants
Secretary
i | 1 qT !
Hospital A Hospital B Hospital C Hospital D
Hospital Team | | | | |
Adm. Asst.
Medical Liaison Officer
Secretary
Lab Technician
16 Nurses
Acute Acute R = reserpine
Disturbed Non-disturbed C = chlorpromazine
RC = combined reserpine
R Cc R _ CS and chlorpromazine
IO 10 10 10 P = placebo
10 10 10 10 - PP = placebo plus psychotherapy
RG PP RC PP
Chronic Chronic
Disturbed Non-disturbed
R Cc R Cc
10 10 10 10
10 10 10 10
RC P RC Pp
Rating Team
Principal Psychiatrist
Assoc. Psychiatrist
Principal Psychologist
Asst. Psychologist
Social Worker
2 Secretaries
L |
Hospital A Hospital B Hospital C Hospital D

Hospital E
Personnel
Central Office

Director -

Advisory Study Group

Statistical Chief

3 Asst. Statisticians
@ $4,500 --

.Secretary

Hospital Teams

Adm. Ass't.

Medical Liaison Officer
Secretary

Lab Technician

16 Nurses @ $4,500 --

Rating Teams

Principal Psychiatrist
Assoc. Psychiatrist
Principal Psychologist
Asst. Psychologist
Social Worker —

- 2 Secretaries @ $3, 500

Equipment

Laboratory Equip. for
technician

Calculators for statis-
ticians

Office furniture for
central office (Director
Chief Statistician, etc.)

Office furniture for rating
teams and hospital teams

Filing cabinets, typewriters,
etc. for central office,
rating teams, hospital

$22,000
3,000
12,000

13,500

3, 500

5,000
10,000
3,500
4,000
72,000

94,500

15,000
10, 000
12,000
8,000
10, 000
7,000

62,000

3,000

500

Zz, 500

BUDGET

54, 000

472,500

310, 000

15, 000

1,500

3,000

25, 000

__3,500

836, 500

48, 000
Rent

 

Central Office
Car for Social Worker

Supplies

Laboratory

Office (Central, Rating

and Hospital)

Medications (Reserpine
and Chlorpromazine)
Travel

Advisory Study Group,

Director, Rating Teams,

Miscellaneous

Cleaning woman, overhead
at hosp. etc.

BUDGET - Continued

3, 000

$1,000 x 5 = 5, 000
500 x 5 = 2,500

6, 500

40, 000

etc.

Page 2.

8, 000

49, 000

25, 000

33,500

$1, 000, 000