(The complete statement of Dr. Kline follows:)

STATEMENT OF NATHAN S. KLINE, DIRECTOR OF RESEARCH, ROCKLAND STATE HOSPITAL, NEW YORK DEPARTMENT OF MENTAL HYGIENE

Before beginning my formal paper may I have permission to submit as exhibit A a curriculum vitae which will provide information as to my qualifications to testify before this committee.

1. Among the other useful results of the present hearings not the least will be to bring again to public attention the enormity of the problem of mental illness, the toll it takes in human and in economic terms-and what is being done about it. There exist little question that mental disease constitutes the Nation's No. 1 public-health problem regardless of how one chooses to define public health. In terms of patient population, of the total hospital beds in the United States, half (i. e., 750,000) are for psychiatric patients. Other hundreds of thousands of patients are treated on an ambulatory basis and probably an even greater number are in need of treatment but facilities are lacking to care for them. On the basis of recent figures it has been estimated that at the present rate of hospitalization one of every 10 persons in the United States will spend part of his life as a patient in a mental hospital. Repeated surveys over the past few decades have shown that of patients coming to the general practitioner approximately one-third have entirely psychological illnesses and another onethird, whatever their physical disability, have emotional and mental complications which seriously interfere with their recovery. Rather than belabor you with a specific breakdown I would like to submit as exhibit B a data sheet prepared by the National Committee Against Mental Illness showing that the economic loss to the country amounts yearly to over $4 billion. Reducing this to a figure which is meaningful to the average individual is a difficult task but as a citizen who pays taxes in the State of New York it is of personal interest to me that roughly one-third of the operating budget of the State goes to the Department of Mental Hygiene and I am sure that the figures for other States whether funds are obtained by direct or indirect taxation are not too different. The cost in human suffering is almost beyond imagination. Mental illness is not a disease which merely effects one member of the family: if the patient is hospitalized the emotional drain on the family who carry this stigma plus the time and effort devoted to visiting and worrying about such a patient may go on not for weeks or months but for years and decades. If the patient is cared for privately the strain on the family in respect to adjusting to living with such an individual plus the economic sacrifices required to provide anything like adequate psychiatric care often leave families in financial and emotional bankruptcy. Under our present system these illnesses are not compensable so that no relief is provided by the ordinary protection against medical disasters.

The diseases which maim and destroy people in the declining years of their life are sad enough but frequently mental illness strikes in adolescence or young adult life and patients who have been hospitalized 50 or even 75 years are not uncommon. If they are married and with children the husband or wife face a difficult future since while the patient still lives one must always hope that something can be done, whereas in illnesses that terminate fatally one must attempt to be reconciled to the inevitable. It is therefore small wonder that any new treatment which offers hope for those who have failed to respond to other methods would be a subject of the greatest public as well as medical interest. Based on available figures it would not be unreasonable to estimate that well over half of the families in the United States had at least one member in a mental hospital or under psychiatric care so that news about advances or dangers of treatment command a tremendous audience with intense personal interest. Until 5 years ago a great majority of mental diseases could not effectively be treated either because no adequate treatment existed or because the available techniques were so time-consuming and expensive that only a handful of the hundreds of thousands of patients could even be tried.

2. In the treatment of infectious diseases the antibiotics clearly marked the beginning of a new era just as the introduction of aseptic techniques sharply demarcate the beginning of modern surgery. There were important developments in the treatment of infectious diseases and in surgery prior to these turning points but the importance of antibiotics and asepsis was so great that they revolutionized all subsequent therapy. The development and successful application of the psychopharmaceuticals was a thermonuclearlike explosion which marked the end of one era and the beginning of another: and which may, in point of fact, be of markedly greater import in the history of mankind than the atom bomb since

if these drugs provide the long awaited key which will unlock the mysteries of the relationship of man's chemical constitution to his psychological behavior and provide effective means of correcting pathological needs there may no longer be any necessity for turning thermonuclear energy to destructive purposes. It is too soon to know whether we are really across the threshold but let me present the evidence for those who hold, as do I, that a major event has occurred in the psychiatric field.

In the 185-year history of the public mental hospitals in the United States at the end of each year there were more patients in the hospitals than there had been at the end of the previous year. In 1956, which was the first year that the drugs were used on a large scale, a simple statement of the facts is the most dramatic way of indicating what happened. The anticipated increase in the mental hospital population of the country was such that at the end of the year there would be between 10,000 and 12,000 patients more in mental hospitals than there had been at the beginning of the year. Instead of this expected increase there was a decrease of over 7,000 patients. In other words, the difference between the expected population and the actual population was almost 20,000 patients. This was not an isolated phenomenon due to an abrupt change in one or two States since in point of fact 43 of the 48 States had less patients than had been anticipated. In New York State where the anticipated increase had been between 2,000 and 2,500 patients there was an actual loss from the hospital roles of some 500 patients—a difference of roughly 3,000. It is impossible to prove that the drugs and the drugs alone were the cause of this unique reversal and undoubtedly the enthusiasm of hospital staffs who found for the first time they had means of treating patients on a large scale-successfully-may have entered into the picture but the burden of proof lies with those who say that the drugs had little or no effect in bringing about this remarkable change. The customary cry of the cynics is that the patients were "pushed out" of the hospitals but this argument is given the lie by the fact that in New York State where discharge increased by 23 percent in the fiscal year 1955-56, the increased rate was maintained during the fiscal year 1956-57. One might "push out" of a hospital a patient who is not ready for discharge but within a few months the community would have forced his return if the improvement existed only in the minds of the hospital staff. The fact that these patients have remained out now for 1 to 2 years is strong indication that some real change has been wrought. Another bit of contributory evidence is the fact that, again in New York State where I know the figures best, the rate of return of patients who are kept on maintenance doses of the pharmaceuticals is roughly half that of patients not on medications. I am well aware that each of these figures may be subjected to statistical criticism on the grounds that this or that factor was not taken fully into account. On the other hand, the evidence is so one-sided and overwhelming that even though one were to make allowance for each of the possibilities in some reasonable proportion the weight of cases is so large that only the most unlikely of accidents could invalidate them. To press for a "congressional analogy" it would be like arguing with three-quarters of the precincts reporting with a majority for one candidate so large that 90 percent of the remaining votes would have to go opposite to the first three-quarters in order for the second candidate to win; to offer all sorts of "plausible" explanations of why the first three-quarters of the precincts reported the way they did with the presentation of "logical" reasons why the remaining one-quarter would vote 90 percent in the opposite direction. As a theoretical consideration no one could say that it was beyond the realm of possibility but it reaches a point where one becomes impatient with such cavilling; with the attitude-let's wait for 20 years before we make a judgment. Reality demands that we accept the fact that the mass of evidence indicates that the drugs are useful and if one wishes to retain reservations that in the long run things may turn out differently than seems to be indicated no one could quarrel since at least one has acted in good faith on the evidence at hand.

Another source of considerable confusion both to psychiatrists and the lay public alike is the claim that while the drugs may reduce symptoms that they do not "cure" the patient. In answer to this there are two important points to make:

1. That with one or two very rare exceptions we know so little about the causes of mental disease that it is completely impossible to talk meaningfully about "cures." The need is for more extensive and intensive research and this point has been recognized fully only in recent years. The magnificent support of the United States Congress has contributed materially to investigations in this area. At the present time the commonsense definition of what is meant by "cure," i. e.,

the relief of symptoms which prevent the individual from useful social function and from enjoyment of life are far more sensible than criteria based on unproven theoretical consideration or the use of unvalidated psychological, physiological, or biochemical tests. With your permission I would like to submit as Exhibit C a paper I published last year entitled, "Criteria for Psychiatric Improvement” which reviews this problem in more detail.

2. In an extremely significant but, I am afraid, overlooked article also published last year, Gruenberg underlines the point that in considering the results of pharmacotherapy one must consider not only complete and final relief of all signs and symptoms of the disease but recognize, as is the case in all other fields of medicine, that reduction of disability is of at least equal importance and that the evidence is overwhelming that here too the psychopharmaceuticals have a major contribution to make.

The fact that thousanus upon thousands of patients are now released from mental hospitals and tens of thousands more have been spared this experience is much more significant than the fact that in a percentage of these patients there are still some residual disabilities of the illness: suffice it to say that many former patients have been able to return to a productive social existence and are receiving a satisfactory amount of enjoyment out of the experience of living.

Even for those patients who must remain institutionalized because our ignorance is still such that we have not devised adequate treatments, a new world has also been created. No longer is the mental hospital racked with wild and meaningless shouting nor do we see any longer the so-called disturbed wards of only a short 5 years ago. As a result of the pharmaceuticals a problem has actually been created since so many patients are now amenable to psychotherapy, occupational therapy, recreational therapy, and other types that the facilities and the personnel for providing these do not exist. It was never anticipated that so large a share of the hospital population would be capable of this type of treatment. Although reduction in mental hospital population has been noted throughout the world wherever these pharmaceuticals were used (and in a few places, like Denmark, there are actually vacancies in some of the mental hospitals for the first time in their history) this does not mean the immediate abolition of the mental hospital as we presently know it. Because of the unfortunate overcrowding it will be a considerable period before the hospitals will ever return to the population for which they were originally built and new and better treatments will have to be devised before the chronic population can be very sizably lessened. The greatest eventual hope is in the adequate treatment of acute patients in order to prevent institutionalization. At the present time a number of us in cooperation with some of the pharmaceutical houses are planning a project which will help determine if this is a feasible and economic way of handling the problems of mental illness, i. e., will the use of adequate pharmaceuticals and good outpatient facilities make it unnecessary to construct large-scale mental hospitals. Such a setup would utilize not only the drugs but psychotherapy and other available techniques since despite the opinion of a few extremists there exists no conflict between psychodynamic and pharmacodynamic treatment. In point of fact they admirably' supplement one another.

A brief mention should also be made of the side effects since these, too, at times are apt to lead to confusion if not properly understood. Any pharmaceutical which possesses potency invariably has side effects. This is merely another way of stating that a pharmaceutical acts at multiple sites and usually is more than one way. Ideally a drug would do only what was therapeutically necessary and no more; but few, if any, compounds of this type exist anywhere in nature or the laboratory. Let me select as a well known example aspirin which has at least two major actions, (1) reduction of pain, (2) reduction of temperature. If the use of the drug is primarily for the relief of pain then the reduction in temperature would be a side effect and, vice versa, if the drug is given for reduction of temperature then reduction of pain sensitivity would be a side effect. Sometimes misunderstanding of this has led to unfortunate publicity. Let us imagine that aspirin was used for a year or so for its pain-reducing properties and only then was it noted that it also reduced body temperature. This might immediately lead to a hue and cry that the drug was potentially dangerous since the normal body temperature was 98.6°F. and the use of aspirin reduced this so that the individual no longer functioned in a normal manner which, since it was below what nature intended, might lead to all sorts of dangerous reactions. Similarly, if the drug were used primarily to reduce temperature and it was subsequently discovered that it also

lessened pain sensitivity, a similar alarm might be sent out that since the individual did not respond to pain in a normal manner he might be subjected to all kinds of accidents and therefore the drug should not be used.

In the case of the psychopharmaceuticals there are similarly side effects but the vast majority of these, although they may be annoying, are not dangerous and to the best of my knowledge (except as noted below) are fully reversible when the medication is discontinued, reduced, or supplementary drugs given to correct the side effects. There are rare side reactions which occasionally are dangerous (as there are with aspirin or any other drug) but if the physician is fully aware of these and on the lookout for their occurrence medication can almost always be reduced or discontinued in time to prevent fatalities. Obviously, medical judgment consists in weighing the advantages to be obtained against the annoyance or danger of the side reactions. This is the so-called calculated risk. It should be stressed that this exists with almost any medical procedure and is by no means limited to drug usage. If a patient has signs and symptoms of an acute appendicitis the surgeon has to make up his mind as to the probability of his diagnosis being correct and the danger of not operating against the dangers which may result from giving the patient anesthesia for the operation, the possibility of a blood clot postoperatively, the risk of something happening during surgery itself and the inconvenience, the psychological effect, and the expense of a week or so of hospitalization plus the convalescent period. There may also be long-term effects of the operation with development of postoperative adhesions which may not become evident until 1, 2 or 5 years later. There have been those who decried the use of the drugs since we do not know what their long-term effect may be. They have not been in use long enough for anyone to demonstrate that after 20 or 30 years there may not be some resultant change but on the other hand, and of even more importance, is the fact that no one has demonstrated that they do have any harmful effect on prolonged usage or on shorter usage after a lapse of many years. I have been told that when insulin was first discovered a Dr. Palmer in Boston raised the same question and at his own time and expense went from one medical society to another arguing against the use of insulin since no one knew what effect it would have at the end of 20 years. His unproven apprehensions, thank goodness, did not prevent general usage of the drug and thereby the lives of tens of thousands of diabetics were saved. Medical judgment almost always tends to be conservative but not reactionary and the widespread use of the drugs indicates that in the considered judgment of most physicians the advantages in the treatment of the patient far outweigh the possibility that there may (or may not) be some long-term effect which has not been discovered.

Another very commonly misunderstood item on this score is addiction to a drug. In popular speech this is used to cover three separate and quite different reactions. The first of these is habit formation to which we are all subject in varying degrees and to all sorts of things. With many of us it is a habit to have orange juice for breakfast and somehow the day does not seem quite right if we do not start it off in this manner. Somehow this orange juice seems to be the approriate thing to drink since it is cool and refreshing and cleans the residual taste of the tooth paste out of our mouth. In a like manner certain individuals will take a sleeping medication or one of the psychopharmaceutical preparations since they have fallen into the habit. Distinct from this is dependence which also applies to many other areas than drugs. There are a large number of individuals who are dependent upon a cup of coffee with which to start their day and who actually are uncivilized until this has been done. If for one or another reason they do not get their coffee they are acutely uncomfortable, have a strong yearning and preoccupation on the subject, and will exert themselves considerably in order to get that essential morning cup of coffee. If for any reason this is unavailable they are irritable and unhappy. This is true also of certain of the psychopharmaceuticals upon which individuals have developed such a dependence. Finally there is true addiction which by medical definition means that if the individual does not receive his accustomed medication there are definite physiological and biochemical reactions causing the person acute physical and psychological distress and even at times endangering his life. In this class would belong such drugs as morphine, codeine, and the barbiturates when used in large doses. It is for this reason that this group of drugs are so closely regulated. Sometimes the term "addiction" is used in its lay meaning by physicians in the same manner that cancer is used to refer to whole groups of malignancies although actually cancer is only one very specific type of neoplasm. Actually one of the major advantages of the psychopharmaceuticals is, that to my knowl edge, there has not been reported a single case of addiction although habit forma

tion and dependence are as common as might be expected. The fact that the sale of barbiturates has dropped well over 50 percent since the introduction of these drugs constitutes a great advance since these individuals are not tempted to barbiturate addiction as they might have been in the past. In addition, there appear to be at least a significant number of individuals who were addicted to alcohol (that is, had habit formation, dependence, etc.) and who are now able to get along with these newer drugs. In summary then, in contrast to preparations such as morphine and the barbiturates when used in large doses, this newer group of pharmaceuticals possess the distinct advantage that there is no evidence that they are addicting in the true meaning of the word.

3. Before passing on to criticisms it should be definitely pointed out what the contributions of the pharmaceutical industry to psychiatry have been. Firstly, without the pharmaceuticals invented and prepared by the drug houses it would have been impossible to achieve the promising results described in the previous paragraphs. These pharmaceuticals were not achieved by accident. As an instance, the development of reserpine by Ciba Pharmaceuticals from the crude root of Rauwolfia serpentina at one time occupied 80 percent of the research capacity of that drug house and involved the expenditure of something over $1 million on the chance that the active ingredient could be isolated and made commercially feasible. It is one of the anomalies of our society that if a firm is successful in producing a product on which it can make money (which is in part used for the development of more such products) that these researchers are not regarded as being as scientifically pure as work done in universities or other institutions. What is most peculiar about this is that we speak constantly of the advantages of a capitalistic free-enterprise system and when we have overwhelming evidence of its successful functioning we tend to disdain advances produced in this manner. The fact that commercial enterprises are able to produce the high quality research results that they do should be a matter of great pride and recognition. The millions of dollars which are invested by drug manufacturing houses in an effort to find newer and more useful products is one of the most important factors which has made it possible for American science to hold such a prominent position in this field.

Secondly, once pharmaceuticals are produced there arises the problem of evaluating them and here again the industry has made a great contribution to psychiatry. At the time we started our own work in Rauwolfia it was almost unheard of for a pharmaceutical house to give any grant support to a State hospital, the line of reasoning running that the institutions were supported by the State, that there was no or almost negative prestige value in making a contribution to research in such backward institutions, and third that the probability of a marketable product coming out of such an exploration was virtually nil. In spite of this Squibb, through its medical director and research grant committee, was willing to venture a small grant to assist our own basic research and to possibly explore whether Rauwolfia root had any effect on psychiatric patients. That the experiment proved interesting and valuable is self-evident. Since that time support in various forms has been given by pharmaceutical house after pharmaceutical house to the various State, county, and similar mental hospitals of the country which has acted as a great stimulus to not only drug evaluation but also to the treatment and general care of patients. As I pointed out in an article last year: "The provision of grants-in-aid 'with no strings attached' has provided an amazing transfusion of vitality into many a struggling clinical or laboratory research group in some clinic or State hospital. Financial watering of this apparently arid region has resulted in the appearance of oases which help to nourish the whole surrounding psychiatric neighborhood. departments of psychiatry and neurology have similarly benefited and, in turn, The university contributed to the greatly expedited attack on the problem. Nor has the research supported by the pharmaceutical houses been limited to clinical testing in the area of biochemistry. Physiological, psychological, and even psychoanalytic projects have been supported. More than one company has adopted the philosophy 'What is good for the field of mental health is ultimately good for us.'"

Thirdly, contrary to the opinion of some, pharmaceutical houses do not limit themselves purely to that which is commercially exploitable. and development of basic research is quite genuine and if occasionally some Their interest "applied" research results this is certainly not to be condemned. cent recognition of iproniazid as a forerunner of a new class of drugs for the Our own retreatment of depression developed, not from the pharmaceutical company which manufactures the product, but from one of their competitors. the laboratories of Warner-Chilcott I chanced to see an experiment in basie While visiting