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Ethics and practice of placebo therapy
Review Ethics and Practice ALAN
of Placebo LESLIE,
Los Angeles,
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often called the healing art, has in the course of events and especially during recent years made striking scientific advances. The art of medicine, in contrast to the science of medicine, was highly developed long ago and consequently has had less room for advancement. The early maturity of this important facet of the practice of medicine was natural enough since prior to the advent of scientific medicine the doctor had a small specific armamentarium and, consciously or not, depended on art for many of his cures. Fortunately for him, patients usually recovered despite such medicaments as the flesh of vipers, the spermatic fluid of frogs, horns of deer, animal excretions, holy oil and many other colorful and often disgusting substances of mystical attributes. These substances could have mitigated suffering only by virtue of their placebo effects. The placebo is as potent today as it was during medical antiquity. Witness the success of witch doctors and other present day practitioners of bizarre forms of healing art who add little more than suggestion to Nature’s potent healing processes. Since these “doctors” are usually unaware that their devices are essentially without intrinsic therapeutic value, they have faith in their methods, which results in a reinforcing of the suggestion with which they treat their followers. Because medicine has been so concerned with its scientific growth too little attention has been paid to advancing the art of medicine, to which therapy with placebos belongs, and consequently knowledge of the use of placebos has not progressed significantly. Nevertheless, placebos are employed by most physicians who treat patients. The paucity of medical writing on the subject, noted by Pepper’ in 1945, constitutes a
Therapy*
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California conspicuous absence particularly if, as concluded by Findley,* the placebo is the most important therapeutic weapon in the hands of even the modern physician. This anomalous state of affairs is at last being corrected. An excellent Cornell Conference on Therapy3 in which placebos were discussed was published in transcription form in 1947 and significant scientific studies of placebos have been reported by Wolf and his associates.“-6 It is surprising that in the light of their importance and everyday use placebos have until so recently been all but neglected in medical curricula and writings. The reasons for this seemingly protracted indifference to so fascinating a topic as the placebo can only be conjectural. If we assume that early healers knew naught of placebos as such (a possibly unjustified assumption), and by consequence did not write about them, why then do we have such a paucity of writings on the subject from latter day medical authors who should be fully aware of the nature of placebos? There is an ethical consideration, current even today, with sharp divergence of opinion concerning the use of the placebo. This in itself should have led to a plethora of spirited writing pro and con but surprisingly has not. Weiss and English7 wrote, “The physician who prescribes placebos, in whatever form, is not consciously dishonest.” The implication that the physician is in any wise dishonest is a serious one but probably not the authors’ intent. They also noted, “The most frequent method of psychotherapy is the giving of placebos,” combined with assurance. As noted by IIymam8 in view of the possible failure of psychotherapy the addition of suggestion to placebo medication is not without danger. It is difficult to see how placebos, because of their very nature, can act independently of suggestion. Perhaps it is merely
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* From the Medical Service, Veterans Administration Center, Los Angeles, Calif., and the Department University of California Medical Center, Los Angeles, Calif.
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a matter of degree. Hyman’s approach to the ethics of the question appears rational in his observation that, although such methods have been attacked by dwellers in ivory towers, they serve a beneficial role in the hands of the modern physician but should be no more than a temporary expedient. I, with many others, believe that the prime roles of the placebo are in the adjuvant therapy of those cases of constitutional disease in which psychic factors play an important contributory part and in research. Pepper’ concerned himself at some length with the etymology and definition of the word, “placebo.” He called it a “humble humbug” and stated that it must be a “medicine without any pharmacologic action whatever.” It is perhaps a humble humbug which, however, requires consummate skill in its administration. But can an effective placebo be without measurable effect? Wolf4 and Wolf and Wolff5 demonstrated measurable changes at end-organs after the administration of placebo drugs. What sets off the neurohumoral mechanism presumably responsible for these changes? It would seem that suggestion is the sine qua non of placebo therapy, the effectiveness of the placebo being directly proportional to the degree of associated suggestion and receptivity of the patient. Conversely, as also shown by Wolf and W01ff,~ the suggestible patient under-reacts to large doses of a potent drug when under the impression that he is receiving a “placebo.” Even noxious effects have been observed after placebo administration;6 Wolf’s subjects reported drowsiness, anorexia, nausea, palpitation, weakness and epigastric pain. Toxic manifestations, including a skin rash, diarrhea, urticaria and angioneurotic edema were objective phenomena illustrating how extremely potent the factor of suggestion can be. The American Illustrated Medical Dictionary9 defines placebo as “an inactive substance or preparation, formerly given to please or gratify a patient, now also used in controlled studies to determine the efficacy of medicinal substances.” WebsterlO says that it is a “medicine or preparation, esp. an inactive one, given merely to satisfy a patient.” These definitions are still less than satisfactory but both include the important limitation to administered, apparently medicinal substances, and exclude psychotherapeutic physical procedures. In other words, although all placebos are psychotherapy, the converse is manifestly not so. The former definition includes one important use of placebos but is still too JUNE,
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limited. In the light of the more modern concept of placebos our definition must be extended, and might be stated somewhat as follows: A placebo is a medicine or preparation which has no inherent pertinent pharmacologic activity but which is effective only by virtue of the factor of suggestion attendant upon its administration. The substance may be ingested, injected, inserted, inhaled or applied. Why do the dwellers in ivory towers decry the use of placebos, if indeed they do? Their opposition appears to stem from a personal philosophy rather than from any objective consideration of carefully documented scientific data. If this is so the controversy cannot be regarded as one of different interpretations placed on freely available scientific evidence but rather as one of differing subjective moralities. This is an unacceptable state of affairs. We admit freely that the caliber of medical practice is not standardized but is variable and ever changing in the direction of improvement. On the other hand, there has long been a high standard of morality among physicians. The Hippocratic Oath embodies it. In the Book of Ecclesiasticus the reader is told to “Honour a physician . . . . for of the most high cometh healing.” Physicians of high principles may have misgivings over giving placebos because their use entails the practice of deception on a patient. Although several physicians with whom I have discussed this point honestly believe that the use of placebos is not deception but merely one form of psychotherapy, I am convinced that this opinion could not have been attained without rationalization. My thesis acknowledges that placebo therapy entails deception, since the patient is led to believe that he has been given a substance of inherent therapeutic value. The abiding question is whether or not such a practice of deception is justifiable on ethical grounds. There is a fine line of distinction between the words, deception and deceit. They are not entirely synonymous since deceit implies blameworthiness whereas deception does not necessarily do so. For example, a sleight-of-hand entertainer practices deception on his audience but only for their amusement, certainly a laudable activity. Can an outright lie be justified by circumstance? As members of society we have been taught that to lie is wrong, but this teaching is not necessarily absolute. For example, if a dangerous paranoiac carrying a gun asks the whereabouts of his fancied persecutor, it is propitious and right to misdirect him.
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The most pointed occasion when the physician must decide whether or not to lie is in the case of the patient with incurable cancer. As individuals, physicians are reluctant to lie but as physicians we must maintain an elasticity of attitude. Plato, l* who dwelt at some length on the deportment of physicians, wrote, “A lie is useful only as a medicine to men. The use of such medicines should be confined to physicians.” Parkinsonn embodied a strong defense of the physician’s integrity in his succinct observation, “The facts are that in clinical science there is devotion to truth and conformity to scientific standards as scrupulous as anywhere, but in practising the art truth has often to be softened.” Incidentally, as Henderson13 suggested, what the doctor believes to be true sometimes isn’t; the patient may thereby be misinformed, albeit unwittingly on the part of the doctor. Also according to Henderson, what the doctor actually says is not in itself important, but rather what the patient comprehends and what it does to him. A physician can usually evade a possibly harmful truth and still satisfy his patient. Such an evasion is on practical grounds preferable to an unequivocal lie, because a lie can be uncovered, and if this should happen the physician will lose the patient’s confidence and respect. If the patient is insistent, there is of course no alternative to the truth. Hippocrates, whose preceptsi are widely considered to be as good today as they were nearly 2,500 years ago, wrote as follows: “Naught should be betrayed to the patient of what may happen or of what may eventually threaten him, because many patients have been driven in this way to extreme measures.” In general, honesty is the best policy, subject to modification according to circumstances. This question in the case of incurable cancer is still moot, and being tangential to the present discussion will not he considered further. Returning to the consideration of deception as applied in medical practice, I will state that I believe deception is completely moral when it is used for the welfare of the patient. If this is admitted, who then is to decide what constitutes the patient’s welfare? Omniscience would be an attribute desirable in any individual responsible for the welfare of another. Being human, however, the physician lacks this quality, but, by the very nature of his position, is the best arbiter of this question when it concerns a patient. Therefore, when the patient’s welfare dictates the use of a placebo there can be no detrimental reflec-
tion on the physician who prescribes it. In fact, the physician who in an appropriate situation refuses to order a placebo, implying in effect that, “I can’t help you because there is no medicine for your disease,” is cruel and is surely not to be praised for his morality. If, in order to avoid giving a placebo, he is so misguided as to prescribe a potent medicament which is not specifically indicated, his position is completely without justification. Neither is it necessary in such a case for the physician to prescribe an “impure” placebo, which in contradistinction to a “pure” placebo contains a substance of some inherent pharmacologic activity not relevant to the immediate problem in order to relieve a tacit feeling of guilt at resorting to placebo therapy. Whether the placebo is pure or impure is of no consequence. What is important is the humane and understanding use of the placebo itself. It is poor practice for the physician to prescribe an impure placebo by virtue of the loose reasoning that the preparation can do no harm and may do some good. Vitamin therapy without specific indication, for example, may actually be good placebo therapy because of the conditioning of the general public to the thought that vitamins have superlative esoteric medicinal properties. Unfortunately, but not uncommonly, the physician himself becomes deluded. After prescribing substances as placebos and observing dramatic (but none the less psychotherapeutic) improvement, he may after repeated successes begin to think, “Maybe we have something here, after all.” Here lies danger, for although by his belief in the potency of his onetime placebo the physician unconsciously reinforces its psychotherapeutic value, the way may be cleared for such impotent therapy to be prescribed in situations calling for specific and potent medicine. Physicians are also subject to a form of mass delusion, which is rarely more than transitory. Our credulity is importuned and exploited by manufacturers of drugs and therapeutic products who enthusiastically bombard us with glowing reports on new remedies. The number of substances which have gone from popularity to oblivion attests to their placebo nature and illustrates the need for the critical evaluation of new agents. Before proceeding to delineate situations in which deception in the form of placebo therapy is indicated, it can be stated almost categorically
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that it is impossible to divorce the component of suggestion, in either favorable or unfavorable direction, from the final therapeutic effect even when avowedly potent substances are administered. The final therapeutic effect is the resultant of the inherent effect of the drug and the effect of suggestion attendant on its administration. By the same token, the regularly observed variation in the effect of any given drug in any individual may depend on the effectiveness of the factor of associated suggestion, conditioned by such variables as the immediate receptivity of the patient, the technic of administration and the environment. INDICATIONS
There are circumstances in which placebos constitute the therapy of choice. In the management of some patients who need support for strong dependency feelings, medication, which is ever the symbol of the doctor, may well have its purpose served by a placebo if no more specific effect is desired. In other circumstances placebos can he important adjuvants to more specific therapy and in fact placebo effects are often gratuitous attributes of specific therapy. Clearly, the placebo is a research tool of prime importance. There is no substitute for the placebo in the “double-blind” evaluation of new drugs. The investigator in such an experiment is naturally aware that a calculated deception is being practiced upon his subject. The subject also may be aware of the game being played; at the discretion of the investigator, however, such information may be withheld. Of real importance in insuring the objectivity of the study is keeping both subject and investigator “blind” so that neither knows whether at any given moment the drug under study or the placebo control is being given. This will minimize the factor of suggestion, either subjective on the part of the patient or unconsciously interjected by the investigator. Another clear indication for placebo therapy occurs in patients who have received sedatives or narcotics in whom the indication for these drugs no longer exists. Following surgery most people require narcotics for variable durations for the control of pain. During periods of stress many people require sedation to relieve anxiety by day and to induce sleep at night. It is quite easy for patients to become dependent on, if not addicted to, these agents. They continue to call for them, perhaps as a mild withdrawal maniTUNE,
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festation. At this stage the substitution of a placebo for a short time is usually all that is necessary for the transition to no medicine. In incurable neoplastic disease there can be no objection to the administration of sufficient sedative and narcotic medication to control all pain and apprehension. There is, nevertheless, the drawback of undesirable associated pharmacologic effects such as constipation and respiratory depression. Since it is possible to raise the pain threshold of most individuals by the use of placebos, it would seem likely that the judicious interpolation of placebos would decrease the narcotic-sedative requirements. The over-all comfort of the patient would thereby be enhanced. Occasionally when a doctor sees a patient fat the first time he finds that the patient has been taking a conglomerate assortment of drugs which have confused the picture by cumulative or additive effects. The dependency of such a patient on his medicines can be transferred to a placebo, so that these confusing, cumulative or additive effects may be dissipated. It thus becomes possible to make a more rational evaluation of the problem which can then be treated directly and more specifically. 0berndorf16 reported a typical case in point. An asthmatic woman who was nearly moribund when first seen had, as is so frequent in individuals with asthma, received a superabundance of medication. Placebos were substituted for epinephrine and sedatives, with salutary effects on the course of the illness. Some people are temperamentally impatient and demand results before they normally would be forthcoming. Occasionally, during a period of diagnostic observation or testing, a placebo will provide a gentle sop to their impatience and keep them under control while the important business is being conducted. The office administration of a placebo injection can serve as the reason to bring a patient for regular, more specific psychotherapy. Now let us examine some situations in which the indications for the use of placebos are perhaps less clear. The management of chronic disease taxes the imagination of the most experienced clinician. Patients with crippling arthritis, paraplegia, hemiplegia, chronic cardiac or pulmonary dyspnea all require prolonged medical attendance. Occasionally, in addition to specific medication an analgesic or sedative drug may be required. Such a drug should not be
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administered for indefinite periods without interruption because there is a remarkably quick conditioning of patients to the sedative or analgesic effect, the associated psychic effect, or a combination of the two. Unless these drugs periods, such are given for strictly limited chronically ill individuals, like the postoperative patient, may become dependent on them. This should not be permitted because of the tolerance developed with consequently increased requirements, as well as undesirable associated pharmacologic effects. Placebos may be helpful in the transition to the acceptable discontinuation of the drug. But we must beware of another real pitfall, which is the development, by conditioning, of dependency on the placebo itself. Whether or not this is undesirable may be argued but in general it is preferable that the patient be well enough adjusted to his disease so he need not depend even on a placebo. From another but practical point of view, in our understaffed institutions for the care of the chronically ill the time needed for the administration of placebos might interfere with more urgent nursing Special situations require special activities. consideration. I am thinking of a sixty year old man with a cardiac aneurysm which developed following a coronary occlusion. After some years of auricular fibrillation and bare maintenance of compensation at absolute rest this man had an aortic saddle embolization which led to gangrene and required amputation of first one then the other leg. During active treatment he received narcotics for which placebo injections were later substituted. Severe unremitting phantom limb pain was unrelieved by local measures and the neurosurgeon could offer only radical neurosurgery, which the patient declined. This man continued to take two daily injections of sterile saline solution, which satisfied him. He had become so dependent on them that he experienced great pain when they were omitted. Because of this man’s underlying chronic disability it was decided to continue the placebos until such time as he might voluntarily relinquish them. There is no unanimity of opinion among psychiatrists about the use of placebos in psychiatry. Some reject them altogether while others believe that they are invaluable in certain instances. In the section on the psychoneuroses in a standard textbook of medicine Rennie16 states that, “Even the placebo, which has no place in psychiatry, can work miracles.” In
reference to the psychoses, Whitehornr7 states that, “Placebo medication has a legitimate diagnostic purpose, but the use of placebos as a regular therapy is of dubious propriety and is unjustified when good psychotherapy is available.” Alvarezrs advises taking away a diagnostic placebo before commencing psychotherapy. Weiss and English’ stated that the answer to the problem of psychogenic illness is correct diagnosis and expressive psychotherapy rather than suppressive psychotherapy, as exemplified by the use of placebos. This might be interpreted as a disavowal of the use of placebos in psychogenic disease, in agreement with one group of psychiatrists. No one will question the importance of correct diagnosis and it is true that the use of placebos is not ideal in many instances of psychogenic disease. It must be remembered, however, that even with a correct diagnosis to work from, it is for manifold reasons frequently impossible to offer a patient the ideal of expressive psychotherapy. If suppressive psychotherapy offers relief but no cure to some of these patients, should it be denied them? If circumstance precludes cure a compromise is obligatory, if without it the idealist turns his back on the reality of a patient seeking relief. I hesitate to enter this controversy and prefer to take a sideline position, hoping meanwhile that our psychiatrist colleagues will debate the technical aspects of the issue. Nevertheless, there is a place for an expression of opinion by the general physician, and as Shawl9 cautioned in 1936, we must avoid overemphasis of either empiricism or rationalism in medicine. Both can contribute to the balanced judgment which will accrue to the patient’s benefit. This principle should apply equally well in psychiatry as it does in medicine, if indeed the two fields can be separated. Whether or not placebos have a role in the therapy of psychotic patients when the psychosis is active, I will also leave for the psychiatrists to decide but I suspect that placebos will be ineffectual and harmless. In the psychoneuroses and occasionally in psychoses in remission, placebos may be of value. Watts and Wilbur20 in discussing the treatment of functional disorders notice that the psychotherapeutic effect of drugs or placebos may be great. If we agree, as I believe we should, that much good can be accomplished and little harm result from properly administered placebo therapy, we will be acting for the welfare of the patient which, AMERICAN
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after all, is our primary objective. Naturally, there must be a good diagnostic evaluation before placebo therapy is selected. The prolonged use of the placebo merely to pacify a patient whose problem is not thoroughly understood cannot be condemned too harshly. Diagnosis often requires observation and repeated examination. The physician who relaxes his diagnostic efforts because the patient appears to respond to a placebo may miss the opportunity to treat a remediable condition. Properly used, the placebo, by allaying fear and providing hope, may help a patient adjust to a conflict situation that cannot be resolved. Since placebos may lose their potency unless periodic reinforcing psychotherapy is forthcoming, the physician must be prepared to provide skillful, long-range care. The symptoms associated with relatively acute organic disease are frequently modified by a greater or lesser degree of psychogenic overlay. This ordinarily does not call for separate handling, since the inseparable beneficial psychic effects of potent medication would also be operative. On occasion, however, it may be desirable to employ some psychotherapeutic potentiation by the use of an appropriate placebo. With a self-limited indication this may be worth while adjuvant therapy. For instance, the use of a “tonic,” such as the elixir of iron, quinine and strychnine, may strengthen a patient convalescing from a febrile or wasting illness if, presumably through a placebo effect, it convinces him that he is hungry and leads to a desirably high calory intake. Intermittent use of this sort of placebo has a place in the care of the chronically ill person if the patient is not allowed to become dependent and then later disillusioned. The use of the placebo as a diagnostic tool has been a subject of considerable debate. There is no question about the diagnostic value of specific therapeutic tests but in light of Wolf and Wolff’s observations of measurable physiologic effects of placebos, opinions concerning the diagnostic value of therapeutic testing with placebos must be modified. Unless responses to placebos used diagnostically are carefully evaluated, serious errors will be made. The absence of response to a placebo favors an organic basis for complaints but positive responses may well be devoid of diagnostic significance and not indicative of psychogenic disease. In principle, therefore, it would appear that placebos properly used have a limited role in JUNE,
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diagnosis and an important one in the management of somatic disease and the psychoneuroses at any time that the affective state of the patient may be beneficially conditioned by this form of suggestion. No doubt there are indications for placebo therapy which have not been specifically considered herein. If so, I implore the indulgence of the critical reader. One repeated word of caution: Placebo therapy should not be ordered unless the physician has examined the indications even more carefully than if he were about to order specific therapy. TECHNIC
In our approach to technics of administration we will assume that we have demonstrated that placebo therapy is justified and has fairly specific indications. The discussion will be simpler if we limit ourselves to our conception of placebo, which predicates that placebos may be ingested, inserted, injected, inhaled or applied. Here there is a wide latitude for individuality of methods so I will not attempt to do more than offer a few illustrative examples, as well as some general “do’s and don’t’s.” Ingested medicines are in the form of liquids, tablets, capsules, pills or powders. Except for gastric antacids, and to a certain extent even here, powders are almost obsolete. Since pills offer no particular advantage over tablets and capsules, which are both easier to swallow and to manufacture, these, too, are being used infrequently. This leaves tablets, capsules and liquids as the oral medications in everyday use. It is only fitting that oral placebos should also be in these forms. People tend to be skeptical of medications which do not look, taste or smell like “medicine.” We have come to associate the warm red-yellowbrown colors with liquids for oral use and the colors blue and green with poisonous or externaluse-only liquids. This, of course, is not absolute but, other things being equal, our liquid placebo should be red, yellow or brown rather than blue or green. The addition of red coloring agents to many liquid medicines is a long-standing, widespread, innocent practice which, incidentally, is officially sanctioned by the U.S.P. and the N.F. in such commonly prescribed preparations as the elixir of phenobarbital which contains 1 per cent of amaranth solution, a red dye, and the alkaline aromatic solution which contains the same dye in
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1.4 per cent concentration. Similarly, a liquid placebo can be given an appropriate taste. Most people over the age of thirty remember how bad tasting medicine used to be. Cod liver oil and the expectorants containing ammonium chloride are two which come quickly to mind. The tinctures of valerian and asafetida were bitter, and in fact were standard placebo medications. Bitterness, rather than ordinary nastiness, carries a strong placebo effect. Modern pharmacies may not stock the old stand-hys hut will he pleased to prepare 0.1 per cent solutions of sodium dehydrocholate which, because of its current use in the determination of circulation time, is available everywhere. This may be colored red, if desired, with something like amaranth solution or tincture of cudbear. When we decide to prescribe a placebo capsule we need not be concerned over the taste, since gelatin capsules are considered to be tasteless. Color, however, is important. A capsule colored red, blue or yellow suggests specific attributes which a transparent, colorless capsule containing a white powder might seem to lack. Furthermore, when it is a question of weaning a patient from barbiturate medication it is relatively simple to substitute a starch or lactose capsule for a barbiturate capsule of identical appearance. Size of medication should be a consideration. Tiny or oversize tablets and capsule may be more impressive than average sized ones, the tiny one suggesting great strength, the jumbo one impressing by its heroic size. Aspirin, although a valuable drug, by being available without prescription has come to be regarded by the public as only a mild remedy. A tablet which resembles aspirin, even if quite potent, will therefore appear undistinguished and consequently lose much of its psychotherapeutic punch. The cutaneous application of placebo substances is an everyday practice. Whereas patients may be reluctant to apply a cold water wet dressing to an inflamed area, they will be perfectly agreeable to applying one containing a dissolved substance. When Epsom salts are added to water, the patient will be properly impressed by the healing virtues of the solution. Although magnesium sulfate is not significantly absorbed through intact skin and does not exert any specific cutaneous effect, cooling evaporation from a dressing open to the air or the moist heat of a hot soak, whichever effect is desired by the physician, still occurs when there is magnesium sulfate in the water. A sore muscle
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group will more readily he kept at desired rest il’ methyl salicylate has been applied to the overlying skin and the region wrapped in flannel, preferably red. If salicylate absorption is desired, aspirin bv mouth would be preferable, for there is no e;idence that methyl salicylatc apphed to the skm is concentrated in the underlying muscle. But the sensation of cutaneous warmth which is due to the irritative erythema, plus the definitive odor, are impressive to all hut the most skeptical. I do not mean to belittle all liniments; they provide lubrication helpful in massage and may just as well smell of wintergreen. Similarly, while a plain hot water mouth wash or gargle would not be respected, a colored one containing a few drops of aromatic oil would be accepted without question. The odor of tincture of henzoin will make the inhalation of steam comprehensible to the average patient. People have by association come to expect this odor and without it they will be reluctant to inhale the steam which alone has the therapeutic value. So we see that the “humble humbug” of Pepper is valuable to induce the patient to take beneficial treatment which otherwise might be neglected. All dermatologists have seen young patients with warts which respond well to the application of almost any substance. This is presumably a placebo effect, since other forms of psychotherapy are equally effective. The spunk water of Huckleberry Finn and Tom Sawyer was undoubtedly as potent as any authoritative prescription preparation. The use of suppositories as placebos should ordinarily be avoided for the same reasons that potent medication given for systemic effect is also better administered by other routes. Conceivably, however, a cocoa butter suppository might be temporarily substituted for one containing aminophyllin if indications for the latter cease to exist and the patient has become dependent. Of these four avenues of drug administration certainly the oral route is for many reasons the simplest and the best for the placebo. But for universal patient acceptance nothing can approach the psychotherapeutic impressiveness of puncture of the integument by a hollow needle. The placebo substance introduced via the needle is usually second in importance to the needle stick. Sherlock Homes called for the needle. Addicts take narcotics by the needle. Pre- and postoperative sedatives and narcotics are injected. Blood is transfused and various solutions
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are infused through needles. Little wonder that there is an association of the injection with powerful medication. The injection requires little or no reinforcing psychotherapy, even with relatively prolonged use. I recall the case of the addict with severe rheumatoid arthritis who “required” 30 mg. of morphine every two hours. After a program of narcotic reduction the patient continued to present himself every two hours for 0.5 cc. of sterile water, saying, “I know you’re not giving me much, Dot, but I’ll take what 1 can get.” The injected placebo may by pharmacologic action impart subjective sensations to the recipient, without any specific therapeutic action. Irritating substances may cause local pain, aside from the trauma of the injection. Even if we grant that there is no danger of tissue necrosis the practice of injecting materials for the specific production of pain as part of the act is to be condemned. We should not allow therapy to be confused with punishment, nor should we appeal to any masochistic individual tendencies. The practice of injecting irritating concentrated solutions of vitamins, in the ahsence of clear-cut signs of vitamin deficiency, is widespread but usually ill advised. But occasionally the indication is specific for just this placebo and when the patient tastes it shortly after the painful injection, he feels doubly ljenefited. A placebo may carry with it the production of other subjective sensations which may potentiate the placebo effect. For example, one action of nicotinic acid is the production of a flush and sensation of heat, desirable therapeutic effects under certain circumstances, undesirable “side” effects under others, but psychotherapeutic when used for that purpose. The intravenous administration of placebo substances is to be criticized since untoward effects sometimes are observed. The type of placebo chosen by the physician depends not only on the situation presented by the patient but on the physician himself and the inescapable patient-doctor relationship or temperamental rapport. As noted by Houston,21 the doctor himself is an important therapeutic agent. It is hard for a doctor to avoid being part actor no matter how he may try. In times past doctors grew beards and wrote prescriptions in Latin, using the apothecary system. This awed a credulous populace and covered some of the gaps in medical knowledge. As we progress it becomes less necessary to resort to this sort of thing. But without carrying it to the point of ,[UNE,
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charlatanism the doctor is more or less effective by his demeanor, whether this is called personality, bedside manner or anything else, and by the way he does and should modify this for each and every patient in order to establish rapport. Whereas the quiet executive is impressed by quiet efficiency, the folksy farmer’s wife might respond only to a warmer, more personal touch. Essentially, there should be provided an atmosphere in which the patient will be receptive to therapy so that the psychotherapeutic aspect of specific medication is not lost and the psychotherapeutic effect of placebo medication is enhanced. Substances which may be harmful or toxic should never be used as placebos. Because of the wide choice of harmless placebos it is unnecessary to court danger. Inorganic arsenical compounds such as Fowler’s solution by mouth or cacodylates by needle have dwindling indications, if indeed indications still remain at all. Physicians formerly believed firmly in their inherent therapeutic value but with more accurate knowledge of pharmacology this belief has been shaken. There is certainly no specific benefit to be anticipated from the administration of inorganic arsenical preparations. They are described as “alteratives” in our older books of materia medica. This is defined as an “obsolete term originally used for drugs said to reestablish healthy functions of the system.“g Some dermatologists continue to use Fowler’s solution in the treatment of recalcitrant dermatoses, clairning occasionally dramatic improvement, without knowing the modus operandi. But we should no longer use these potentially toxic compounds in a confused way as a sort of impure placebo. It is desirable in patients who respond well (0 placebo therapy to prevent their becoming dependent on placebos. These individuals, considered as a group, are more dependent than most people. The use of placebos supplies a socially acceptable substitute dependency when more profound psychotherapy is not available. Consequently these patients are frequently content to take placebos almost indefinitely. II placebo administration is prolonged, dependent) becomes physiologic, as well as psychologic, as illustrated by characteristic withdrawal phenomena when a placebo narcotic-substitute is discontinued. Since, as already noted, dependency on placebos is undoubtedly less undesirahle than addiction to narcotics, there is justification for their prolonged administration in some cases. But in addition to the question of the propriety
Ethics and Practice of Placebo Therapy-Leslie of allowing a patient to become dependent on the placebo there is always the question of the feasibility of maintaining him satisfactorily on a placebo regimen. This must be resolved on an individual basis and requires careful evaluation and perhaps a period of trial. When the decision has been reached to discontinue placebo medication, the procedure to be employed depends on the relationship of doctor and patient. The patient’s dependency is divided between the doctor and the placebo doctor-symbol. If the former predominates, the problem is relatively simple; if the latter predominates, the difficulty may be very great. The technic employed must be adapted to the specific situation. One warning is in order. The doctor who gives a placebo should never allow himself to appear hostile to a patient at the proposed time of discontinuing it by triumphantly telling him that he wasn’t getting anything but water, lactose or whatever the substance might have been. The man who has used a wheelchair and is being encouraged to walk would fall flat if not given crutches or a cane for support. Similarly, the patient who has leaned on a placebo must not have this support rudely knocked out from under him without some transitional device. Some individuals may be told, if circumstances warrant their being given this information, that they had received placebos to help them away from narcotics or sedatives. Others should never be told that their precious medicine was a hoax. No rule of preselection of patients can be laid down; each doctor treats each patient in his own most effective way. CONCLUDING
REMARKS
In our discussion we have attempted first to establish that the use of the placebo entails the use of deception, then that this deception is permissible since it is for the benefit of the patient. We have defined placebo as “a medicine or preparation which has no inherent pertinent pharmacologic activity but which is effective only by virtue of the factor of suggestion attendant upon its administration.” Placebos are useful in diagnosis, therapy and research. When a placebo is indicated as principal or associated psychotherapy it should not be withheld, but the physician must be alert to the limitations of this form of therapy. The specific technic is largely a matter of personal choice, depending on the physician’s rapport with the patient. The physician should be
sensitive to changes in his patient which would point to a change in or discontinuation of such therapy. The principles set forth are not intended as inviolate rules but only as guides to be modified according to the needs of the individual patient as appraised by the individual physician. The proper use of the placebo requires, in addition to broad medical knowledge, a depth of human understanding not requisite to the purely materialistic approach to medicine. REFERENCES 1. 2. 3. 4.
5.
6. 7. 8. 9.
10.
11. 12. 13.
14.
15. 16.
17.
18. 19. 20. 21.
0. H. P. A note on the placebo. Tr. &’ Stud., Coil. Physicians, Philadelphia, 13: 81, 1945. FINDLEY, T. The placebo and the physician. M. C/in. North America, 37: 1821, 1953. Cornell Conferences on Therapy. The use of placebos in therapy. 2: 1, 1947. WOLF, S. Effects of suggestion and conditioning on the action of chemical agents in human subjectsthe pharmacology of placebos. J. Clin. Investigation, 29: 100, 1950. WOLF, S. and WOLFF, H. G. Human Gastric Function, 2nd ed., p. 170. New York and London, 1947. Oxford. WOLF, S. Toxic effect of placebo administration. C&n. Research Proc.. 1: 117. 1953. WEISS, E. and ENOL& 0. S. Psychosomatic Medicine. Philadelphia, 1947. W. B. Saunders & Co. HYMAN, H. T. An Integrated Practice of Medicine. Philadelnhia. 1947. W. B. Saunders & Co. DORLAND,-W. A. N. The American Illustrated Medical Dictionary, 22nd ed. Philadelphia, 1951. W. B. Saunders & Co. Webster’s New International Dictionary of the English Language, 2nd ed. Springfield, Mass., 1947. G. C. Merriam Co. PLATO. The Republic. PARKINSON,J. The patient and the physician. Ann. Int. Med., 35: 307, 1951. HENDERSON,L. J. Quoted by Means, J. H. Evolution of the doctor-patient relationship. Bull. New York Acad. Med., 29: 725, 1953. Hippocrates. Quoted by Castiglioni, A. A History of Medicine, 2nd ed. New York, 1947. Alfred A. Knopf. OBERNDORP, C. P. Psychogenic factors in asthma. New YorkState J. Med., 35: 41, 1935, RENNIE, T. A. C. In: A Textbook of Medicine, 8tNed. (Cecil, R. A. and Loeb, R. F.). Philadelphia, 1951. W. B. Saunders & Co. WHITEHORN,J. C. In a Textbook of Medicine, 8th ed. (Cecil, R. A. and Loeb, R. F.). Philadelphia, 1951. W. B. Saunders & Co. ALVAREZ, W. C. The Neuroses. Philadelphia, 1951. W. B. Saunders & Co. SHAW, M. E. Medical facts and fallacies. Brit. M. J., 1: 515, 1936. WATTS, M. S. M. and WILBUR, D. L. Treatment of functional disorders. J. A. M. A., 152: 1192, 1953. HOUSTON,W. R. The doctor himself as a therapeutic agent. Ann. Znt. Med., 11: 1416, 1938. PEPPER,
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often called the healing art, has in the course of events and especially during recent years made striking scientific advances. The art of medicine, in contrast to the science of medicine, was highly developed long ago and consequently has had less room for advancement. The early maturity of this important facet of the practice of medicine was natural enough since prior to the advent of scientific medicine the doctor had a small specific armamentarium and, consciously or not, depended on art for many of his cures. Fortunately for him, patients usually recovered despite such medicaments as the flesh of vipers, the spermatic fluid of frogs, horns of deer, animal excretions, holy oil and many other colorful and often disgusting substances of mystical attributes. These substances could have mitigated suffering only by virtue of their placebo effects. The placebo is as potent today as it was during medical antiquity. Witness the success of witch doctors and other present day practitioners of bizarre forms of healing art who add little more than suggestion to Nature’s potent healing processes. Since these “doctors” are usually unaware that their devices are essentially without intrinsic therapeutic value, they have faith in their methods, which results in a reinforcing of the suggestion with which they treat their followers. Because medicine has been so concerned with its scientific growth too little attention has been paid to advancing the art of medicine, to which therapy with placebos belongs, and consequently knowledge of the use of placebos has not progressed significantly. Nevertheless, placebos are employed by most physicians who treat patients. The paucity of medical writing on the subject, noted by Pepper’ in 1945, constitutes a
Therapy*
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California conspicuous absence particularly if, as concluded by Findley,* the placebo is the most important therapeutic weapon in the hands of even the modern physician. This anomalous state of affairs is at last being corrected. An excellent Cornell Conference on Therapy3 in which placebos were discussed was published in transcription form in 1947 and significant scientific studies of placebos have been reported by Wolf and his associates.“-6 It is surprising that in the light of their importance and everyday use placebos have until so recently been all but neglected in medical curricula and writings. The reasons for this seemingly protracted indifference to so fascinating a topic as the placebo can only be conjectural. If we assume that early healers knew naught of placebos as such (a possibly unjustified assumption), and by consequence did not write about them, why then do we have such a paucity of writings on the subject from latter day medical authors who should be fully aware of the nature of placebos? There is an ethical consideration, current even today, with sharp divergence of opinion concerning the use of the placebo. This in itself should have led to a plethora of spirited writing pro and con but surprisingly has not. Weiss and English7 wrote, “The physician who prescribes placebos, in whatever form, is not consciously dishonest.” The implication that the physician is in any wise dishonest is a serious one but probably not the authors’ intent. They also noted, “The most frequent method of psychotherapy is the giving of placebos,” combined with assurance. As noted by IIymam8 in view of the possible failure of psychotherapy the addition of suggestion to placebo medication is not without danger. It is difficult to see how placebos, because of their very nature, can act independently of suggestion. Perhaps it is merely
EDICINE,
* From the Medical Service, Veterans Administration Center, Los Angeles, Calif., and the Department University of California Medical Center, Los Angeles, Calif.
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a matter of degree. Hyman’s approach to the ethics of the question appears rational in his observation that, although such methods have been attacked by dwellers in ivory towers, they serve a beneficial role in the hands of the modern physician but should be no more than a temporary expedient. I, with many others, believe that the prime roles of the placebo are in the adjuvant therapy of those cases of constitutional disease in which psychic factors play an important contributory part and in research. Pepper’ concerned himself at some length with the etymology and definition of the word, “placebo.” He called it a “humble humbug” and stated that it must be a “medicine without any pharmacologic action whatever.” It is perhaps a humble humbug which, however, requires consummate skill in its administration. But can an effective placebo be without measurable effect? Wolf4 and Wolf and Wolff5 demonstrated measurable changes at end-organs after the administration of placebo drugs. What sets off the neurohumoral mechanism presumably responsible for these changes? It would seem that suggestion is the sine qua non of placebo therapy, the effectiveness of the placebo being directly proportional to the degree of associated suggestion and receptivity of the patient. Conversely, as also shown by Wolf and W01ff,~ the suggestible patient under-reacts to large doses of a potent drug when under the impression that he is receiving a “placebo.” Even noxious effects have been observed after placebo administration;6 Wolf’s subjects reported drowsiness, anorexia, nausea, palpitation, weakness and epigastric pain. Toxic manifestations, including a skin rash, diarrhea, urticaria and angioneurotic edema were objective phenomena illustrating how extremely potent the factor of suggestion can be. The American Illustrated Medical Dictionary9 defines placebo as “an inactive substance or preparation, formerly given to please or gratify a patient, now also used in controlled studies to determine the efficacy of medicinal substances.” WebsterlO says that it is a “medicine or preparation, esp. an inactive one, given merely to satisfy a patient.” These definitions are still less than satisfactory but both include the important limitation to administered, apparently medicinal substances, and exclude psychotherapeutic physical procedures. In other words, although all placebos are psychotherapy, the converse is manifestly not so. The former definition includes one important use of placebos but is still too JUNE,
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limited. In the light of the more modern concept of placebos our definition must be extended, and might be stated somewhat as follows: A placebo is a medicine or preparation which has no inherent pertinent pharmacologic activity but which is effective only by virtue of the factor of suggestion attendant upon its administration. The substance may be ingested, injected, inserted, inhaled or applied. Why do the dwellers in ivory towers decry the use of placebos, if indeed they do? Their opposition appears to stem from a personal philosophy rather than from any objective consideration of carefully documented scientific data. If this is so the controversy cannot be regarded as one of different interpretations placed on freely available scientific evidence but rather as one of differing subjective moralities. This is an unacceptable state of affairs. We admit freely that the caliber of medical practice is not standardized but is variable and ever changing in the direction of improvement. On the other hand, there has long been a high standard of morality among physicians. The Hippocratic Oath embodies it. In the Book of Ecclesiasticus the reader is told to “Honour a physician . . . . for of the most high cometh healing.” Physicians of high principles may have misgivings over giving placebos because their use entails the practice of deception on a patient. Although several physicians with whom I have discussed this point honestly believe that the use of placebos is not deception but merely one form of psychotherapy, I am convinced that this opinion could not have been attained without rationalization. My thesis acknowledges that placebo therapy entails deception, since the patient is led to believe that he has been given a substance of inherent therapeutic value. The abiding question is whether or not such a practice of deception is justifiable on ethical grounds. There is a fine line of distinction between the words, deception and deceit. They are not entirely synonymous since deceit implies blameworthiness whereas deception does not necessarily do so. For example, a sleight-of-hand entertainer practices deception on his audience but only for their amusement, certainly a laudable activity. Can an outright lie be justified by circumstance? As members of society we have been taught that to lie is wrong, but this teaching is not necessarily absolute. For example, if a dangerous paranoiac carrying a gun asks the whereabouts of his fancied persecutor, it is propitious and right to misdirect him.
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The most pointed occasion when the physician must decide whether or not to lie is in the case of the patient with incurable cancer. As individuals, physicians are reluctant to lie but as physicians we must maintain an elasticity of attitude. Plato, l* who dwelt at some length on the deportment of physicians, wrote, “A lie is useful only as a medicine to men. The use of such medicines should be confined to physicians.” Parkinsonn embodied a strong defense of the physician’s integrity in his succinct observation, “The facts are that in clinical science there is devotion to truth and conformity to scientific standards as scrupulous as anywhere, but in practising the art truth has often to be softened.” Incidentally, as Henderson13 suggested, what the doctor believes to be true sometimes isn’t; the patient may thereby be misinformed, albeit unwittingly on the part of the doctor. Also according to Henderson, what the doctor actually says is not in itself important, but rather what the patient comprehends and what it does to him. A physician can usually evade a possibly harmful truth and still satisfy his patient. Such an evasion is on practical grounds preferable to an unequivocal lie, because a lie can be uncovered, and if this should happen the physician will lose the patient’s confidence and respect. If the patient is insistent, there is of course no alternative to the truth. Hippocrates, whose preceptsi are widely considered to be as good today as they were nearly 2,500 years ago, wrote as follows: “Naught should be betrayed to the patient of what may happen or of what may eventually threaten him, because many patients have been driven in this way to extreme measures.” In general, honesty is the best policy, subject to modification according to circumstances. This question in the case of incurable cancer is still moot, and being tangential to the present discussion will not he considered further. Returning to the consideration of deception as applied in medical practice, I will state that I believe deception is completely moral when it is used for the welfare of the patient. If this is admitted, who then is to decide what constitutes the patient’s welfare? Omniscience would be an attribute desirable in any individual responsible for the welfare of another. Being human, however, the physician lacks this quality, but, by the very nature of his position, is the best arbiter of this question when it concerns a patient. Therefore, when the patient’s welfare dictates the use of a placebo there can be no detrimental reflec-
tion on the physician who prescribes it. In fact, the physician who in an appropriate situation refuses to order a placebo, implying in effect that, “I can’t help you because there is no medicine for your disease,” is cruel and is surely not to be praised for his morality. If, in order to avoid giving a placebo, he is so misguided as to prescribe a potent medicament which is not specifically indicated, his position is completely without justification. Neither is it necessary in such a case for the physician to prescribe an “impure” placebo, which in contradistinction to a “pure” placebo contains a substance of some inherent pharmacologic activity not relevant to the immediate problem in order to relieve a tacit feeling of guilt at resorting to placebo therapy. Whether the placebo is pure or impure is of no consequence. What is important is the humane and understanding use of the placebo itself. It is poor practice for the physician to prescribe an impure placebo by virtue of the loose reasoning that the preparation can do no harm and may do some good. Vitamin therapy without specific indication, for example, may actually be good placebo therapy because of the conditioning of the general public to the thought that vitamins have superlative esoteric medicinal properties. Unfortunately, but not uncommonly, the physician himself becomes deluded. After prescribing substances as placebos and observing dramatic (but none the less psychotherapeutic) improvement, he may after repeated successes begin to think, “Maybe we have something here, after all.” Here lies danger, for although by his belief in the potency of his onetime placebo the physician unconsciously reinforces its psychotherapeutic value, the way may be cleared for such impotent therapy to be prescribed in situations calling for specific and potent medicine. Physicians are also subject to a form of mass delusion, which is rarely more than transitory. Our credulity is importuned and exploited by manufacturers of drugs and therapeutic products who enthusiastically bombard us with glowing reports on new remedies. The number of substances which have gone from popularity to oblivion attests to their placebo nature and illustrates the need for the critical evaluation of new agents. Before proceeding to delineate situations in which deception in the form of placebo therapy is indicated, it can be stated almost categorically
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that it is impossible to divorce the component of suggestion, in either favorable or unfavorable direction, from the final therapeutic effect even when avowedly potent substances are administered. The final therapeutic effect is the resultant of the inherent effect of the drug and the effect of suggestion attendant on its administration. By the same token, the regularly observed variation in the effect of any given drug in any individual may depend on the effectiveness of the factor of associated suggestion, conditioned by such variables as the immediate receptivity of the patient, the technic of administration and the environment. INDICATIONS
There are circumstances in which placebos constitute the therapy of choice. In the management of some patients who need support for strong dependency feelings, medication, which is ever the symbol of the doctor, may well have its purpose served by a placebo if no more specific effect is desired. In other circumstances placebos can he important adjuvants to more specific therapy and in fact placebo effects are often gratuitous attributes of specific therapy. Clearly, the placebo is a research tool of prime importance. There is no substitute for the placebo in the “double-blind” evaluation of new drugs. The investigator in such an experiment is naturally aware that a calculated deception is being practiced upon his subject. The subject also may be aware of the game being played; at the discretion of the investigator, however, such information may be withheld. Of real importance in insuring the objectivity of the study is keeping both subject and investigator “blind” so that neither knows whether at any given moment the drug under study or the placebo control is being given. This will minimize the factor of suggestion, either subjective on the part of the patient or unconsciously interjected by the investigator. Another clear indication for placebo therapy occurs in patients who have received sedatives or narcotics in whom the indication for these drugs no longer exists. Following surgery most people require narcotics for variable durations for the control of pain. During periods of stress many people require sedation to relieve anxiety by day and to induce sleep at night. It is quite easy for patients to become dependent on, if not addicted to, these agents. They continue to call for them, perhaps as a mild withdrawal maniTUNE,
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festation. At this stage the substitution of a placebo for a short time is usually all that is necessary for the transition to no medicine. In incurable neoplastic disease there can be no objection to the administration of sufficient sedative and narcotic medication to control all pain and apprehension. There is, nevertheless, the drawback of undesirable associated pharmacologic effects such as constipation and respiratory depression. Since it is possible to raise the pain threshold of most individuals by the use of placebos, it would seem likely that the judicious interpolation of placebos would decrease the narcotic-sedative requirements. The over-all comfort of the patient would thereby be enhanced. Occasionally when a doctor sees a patient fat the first time he finds that the patient has been taking a conglomerate assortment of drugs which have confused the picture by cumulative or additive effects. The dependency of such a patient on his medicines can be transferred to a placebo, so that these confusing, cumulative or additive effects may be dissipated. It thus becomes possible to make a more rational evaluation of the problem which can then be treated directly and more specifically. 0berndorf16 reported a typical case in point. An asthmatic woman who was nearly moribund when first seen had, as is so frequent in individuals with asthma, received a superabundance of medication. Placebos were substituted for epinephrine and sedatives, with salutary effects on the course of the illness. Some people are temperamentally impatient and demand results before they normally would be forthcoming. Occasionally, during a period of diagnostic observation or testing, a placebo will provide a gentle sop to their impatience and keep them under control while the important business is being conducted. The office administration of a placebo injection can serve as the reason to bring a patient for regular, more specific psychotherapy. Now let us examine some situations in which the indications for the use of placebos are perhaps less clear. The management of chronic disease taxes the imagination of the most experienced clinician. Patients with crippling arthritis, paraplegia, hemiplegia, chronic cardiac or pulmonary dyspnea all require prolonged medical attendance. Occasionally, in addition to specific medication an analgesic or sedative drug may be required. Such a drug should not be
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administered for indefinite periods without interruption because there is a remarkably quick conditioning of patients to the sedative or analgesic effect, the associated psychic effect, or a combination of the two. Unless these drugs periods, such are given for strictly limited chronically ill individuals, like the postoperative patient, may become dependent on them. This should not be permitted because of the tolerance developed with consequently increased requirements, as well as undesirable associated pharmacologic effects. Placebos may be helpful in the transition to the acceptable discontinuation of the drug. But we must beware of another real pitfall, which is the development, by conditioning, of dependency on the placebo itself. Whether or not this is undesirable may be argued but in general it is preferable that the patient be well enough adjusted to his disease so he need not depend even on a placebo. From another but practical point of view, in our understaffed institutions for the care of the chronically ill the time needed for the administration of placebos might interfere with more urgent nursing Special situations require special activities. consideration. I am thinking of a sixty year old man with a cardiac aneurysm which developed following a coronary occlusion. After some years of auricular fibrillation and bare maintenance of compensation at absolute rest this man had an aortic saddle embolization which led to gangrene and required amputation of first one then the other leg. During active treatment he received narcotics for which placebo injections were later substituted. Severe unremitting phantom limb pain was unrelieved by local measures and the neurosurgeon could offer only radical neurosurgery, which the patient declined. This man continued to take two daily injections of sterile saline solution, which satisfied him. He had become so dependent on them that he experienced great pain when they were omitted. Because of this man’s underlying chronic disability it was decided to continue the placebos until such time as he might voluntarily relinquish them. There is no unanimity of opinion among psychiatrists about the use of placebos in psychiatry. Some reject them altogether while others believe that they are invaluable in certain instances. In the section on the psychoneuroses in a standard textbook of medicine Rennie16 states that, “Even the placebo, which has no place in psychiatry, can work miracles.” In
reference to the psychoses, Whitehornr7 states that, “Placebo medication has a legitimate diagnostic purpose, but the use of placebos as a regular therapy is of dubious propriety and is unjustified when good psychotherapy is available.” Alvarezrs advises taking away a diagnostic placebo before commencing psychotherapy. Weiss and English’ stated that the answer to the problem of psychogenic illness is correct diagnosis and expressive psychotherapy rather than suppressive psychotherapy, as exemplified by the use of placebos. This might be interpreted as a disavowal of the use of placebos in psychogenic disease, in agreement with one group of psychiatrists. No one will question the importance of correct diagnosis and it is true that the use of placebos is not ideal in many instances of psychogenic disease. It must be remembered, however, that even with a correct diagnosis to work from, it is for manifold reasons frequently impossible to offer a patient the ideal of expressive psychotherapy. If suppressive psychotherapy offers relief but no cure to some of these patients, should it be denied them? If circumstance precludes cure a compromise is obligatory, if without it the idealist turns his back on the reality of a patient seeking relief. I hesitate to enter this controversy and prefer to take a sideline position, hoping meanwhile that our psychiatrist colleagues will debate the technical aspects of the issue. Nevertheless, there is a place for an expression of opinion by the general physician, and as Shawl9 cautioned in 1936, we must avoid overemphasis of either empiricism or rationalism in medicine. Both can contribute to the balanced judgment which will accrue to the patient’s benefit. This principle should apply equally well in psychiatry as it does in medicine, if indeed the two fields can be separated. Whether or not placebos have a role in the therapy of psychotic patients when the psychosis is active, I will also leave for the psychiatrists to decide but I suspect that placebos will be ineffectual and harmless. In the psychoneuroses and occasionally in psychoses in remission, placebos may be of value. Watts and Wilbur20 in discussing the treatment of functional disorders notice that the psychotherapeutic effect of drugs or placebos may be great. If we agree, as I believe we should, that much good can be accomplished and little harm result from properly administered placebo therapy, we will be acting for the welfare of the patient which, AMERICAN
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after all, is our primary objective. Naturally, there must be a good diagnostic evaluation before placebo therapy is selected. The prolonged use of the placebo merely to pacify a patient whose problem is not thoroughly understood cannot be condemned too harshly. Diagnosis often requires observation and repeated examination. The physician who relaxes his diagnostic efforts because the patient appears to respond to a placebo may miss the opportunity to treat a remediable condition. Properly used, the placebo, by allaying fear and providing hope, may help a patient adjust to a conflict situation that cannot be resolved. Since placebos may lose their potency unless periodic reinforcing psychotherapy is forthcoming, the physician must be prepared to provide skillful, long-range care. The symptoms associated with relatively acute organic disease are frequently modified by a greater or lesser degree of psychogenic overlay. This ordinarily does not call for separate handling, since the inseparable beneficial psychic effects of potent medication would also be operative. On occasion, however, it may be desirable to employ some psychotherapeutic potentiation by the use of an appropriate placebo. With a self-limited indication this may be worth while adjuvant therapy. For instance, the use of a “tonic,” such as the elixir of iron, quinine and strychnine, may strengthen a patient convalescing from a febrile or wasting illness if, presumably through a placebo effect, it convinces him that he is hungry and leads to a desirably high calory intake. Intermittent use of this sort of placebo has a place in the care of the chronically ill person if the patient is not allowed to become dependent and then later disillusioned. The use of the placebo as a diagnostic tool has been a subject of considerable debate. There is no question about the diagnostic value of specific therapeutic tests but in light of Wolf and Wolff’s observations of measurable physiologic effects of placebos, opinions concerning the diagnostic value of therapeutic testing with placebos must be modified. Unless responses to placebos used diagnostically are carefully evaluated, serious errors will be made. The absence of response to a placebo favors an organic basis for complaints but positive responses may well be devoid of diagnostic significance and not indicative of psychogenic disease. In principle, therefore, it would appear that placebos properly used have a limited role in JUNE,
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diagnosis and an important one in the management of somatic disease and the psychoneuroses at any time that the affective state of the patient may be beneficially conditioned by this form of suggestion. No doubt there are indications for placebo therapy which have not been specifically considered herein. If so, I implore the indulgence of the critical reader. One repeated word of caution: Placebo therapy should not be ordered unless the physician has examined the indications even more carefully than if he were about to order specific therapy. TECHNIC
In our approach to technics of administration we will assume that we have demonstrated that placebo therapy is justified and has fairly specific indications. The discussion will be simpler if we limit ourselves to our conception of placebo, which predicates that placebos may be ingested, inserted, injected, inhaled or applied. Here there is a wide latitude for individuality of methods so I will not attempt to do more than offer a few illustrative examples, as well as some general “do’s and don’t’s.” Ingested medicines are in the form of liquids, tablets, capsules, pills or powders. Except for gastric antacids, and to a certain extent even here, powders are almost obsolete. Since pills offer no particular advantage over tablets and capsules, which are both easier to swallow and to manufacture, these, too, are being used infrequently. This leaves tablets, capsules and liquids as the oral medications in everyday use. It is only fitting that oral placebos should also be in these forms. People tend to be skeptical of medications which do not look, taste or smell like “medicine.” We have come to associate the warm red-yellowbrown colors with liquids for oral use and the colors blue and green with poisonous or externaluse-only liquids. This, of course, is not absolute but, other things being equal, our liquid placebo should be red, yellow or brown rather than blue or green. The addition of red coloring agents to many liquid medicines is a long-standing, widespread, innocent practice which, incidentally, is officially sanctioned by the U.S.P. and the N.F. in such commonly prescribed preparations as the elixir of phenobarbital which contains 1 per cent of amaranth solution, a red dye, and the alkaline aromatic solution which contains the same dye in
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1.4 per cent concentration. Similarly, a liquid placebo can be given an appropriate taste. Most people over the age of thirty remember how bad tasting medicine used to be. Cod liver oil and the expectorants containing ammonium chloride are two which come quickly to mind. The tinctures of valerian and asafetida were bitter, and in fact were standard placebo medications. Bitterness, rather than ordinary nastiness, carries a strong placebo effect. Modern pharmacies may not stock the old stand-hys hut will he pleased to prepare 0.1 per cent solutions of sodium dehydrocholate which, because of its current use in the determination of circulation time, is available everywhere. This may be colored red, if desired, with something like amaranth solution or tincture of cudbear. When we decide to prescribe a placebo capsule we need not be concerned over the taste, since gelatin capsules are considered to be tasteless. Color, however, is important. A capsule colored red, blue or yellow suggests specific attributes which a transparent, colorless capsule containing a white powder might seem to lack. Furthermore, when it is a question of weaning a patient from barbiturate medication it is relatively simple to substitute a starch or lactose capsule for a barbiturate capsule of identical appearance. Size of medication should be a consideration. Tiny or oversize tablets and capsule may be more impressive than average sized ones, the tiny one suggesting great strength, the jumbo one impressing by its heroic size. Aspirin, although a valuable drug, by being available without prescription has come to be regarded by the public as only a mild remedy. A tablet which resembles aspirin, even if quite potent, will therefore appear undistinguished and consequently lose much of its psychotherapeutic punch. The cutaneous application of placebo substances is an everyday practice. Whereas patients may be reluctant to apply a cold water wet dressing to an inflamed area, they will be perfectly agreeable to applying one containing a dissolved substance. When Epsom salts are added to water, the patient will be properly impressed by the healing virtues of the solution. Although magnesium sulfate is not significantly absorbed through intact skin and does not exert any specific cutaneous effect, cooling evaporation from a dressing open to the air or the moist heat of a hot soak, whichever effect is desired by the physician, still occurs when there is magnesium sulfate in the water. A sore muscle
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group will more readily he kept at desired rest il’ methyl salicylate has been applied to the overlying skin and the region wrapped in flannel, preferably red. If salicylate absorption is desired, aspirin bv mouth would be preferable, for there is no e;idence that methyl salicylatc apphed to the skm is concentrated in the underlying muscle. But the sensation of cutaneous warmth which is due to the irritative erythema, plus the definitive odor, are impressive to all hut the most skeptical. I do not mean to belittle all liniments; they provide lubrication helpful in massage and may just as well smell of wintergreen. Similarly, while a plain hot water mouth wash or gargle would not be respected, a colored one containing a few drops of aromatic oil would be accepted without question. The odor of tincture of henzoin will make the inhalation of steam comprehensible to the average patient. People have by association come to expect this odor and without it they will be reluctant to inhale the steam which alone has the therapeutic value. So we see that the “humble humbug” of Pepper is valuable to induce the patient to take beneficial treatment which otherwise might be neglected. All dermatologists have seen young patients with warts which respond well to the application of almost any substance. This is presumably a placebo effect, since other forms of psychotherapy are equally effective. The spunk water of Huckleberry Finn and Tom Sawyer was undoubtedly as potent as any authoritative prescription preparation. The use of suppositories as placebos should ordinarily be avoided for the same reasons that potent medication given for systemic effect is also better administered by other routes. Conceivably, however, a cocoa butter suppository might be temporarily substituted for one containing aminophyllin if indications for the latter cease to exist and the patient has become dependent. Of these four avenues of drug administration certainly the oral route is for many reasons the simplest and the best for the placebo. But for universal patient acceptance nothing can approach the psychotherapeutic impressiveness of puncture of the integument by a hollow needle. The placebo substance introduced via the needle is usually second in importance to the needle stick. Sherlock Homes called for the needle. Addicts take narcotics by the needle. Pre- and postoperative sedatives and narcotics are injected. Blood is transfused and various solutions
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are infused through needles. Little wonder that there is an association of the injection with powerful medication. The injection requires little or no reinforcing psychotherapy, even with relatively prolonged use. I recall the case of the addict with severe rheumatoid arthritis who “required” 30 mg. of morphine every two hours. After a program of narcotic reduction the patient continued to present himself every two hours for 0.5 cc. of sterile water, saying, “I know you’re not giving me much, Dot, but I’ll take what 1 can get.” The injected placebo may by pharmacologic action impart subjective sensations to the recipient, without any specific therapeutic action. Irritating substances may cause local pain, aside from the trauma of the injection. Even if we grant that there is no danger of tissue necrosis the practice of injecting materials for the specific production of pain as part of the act is to be condemned. We should not allow therapy to be confused with punishment, nor should we appeal to any masochistic individual tendencies. The practice of injecting irritating concentrated solutions of vitamins, in the ahsence of clear-cut signs of vitamin deficiency, is widespread but usually ill advised. But occasionally the indication is specific for just this placebo and when the patient tastes it shortly after the painful injection, he feels doubly ljenefited. A placebo may carry with it the production of other subjective sensations which may potentiate the placebo effect. For example, one action of nicotinic acid is the production of a flush and sensation of heat, desirable therapeutic effects under certain circumstances, undesirable “side” effects under others, but psychotherapeutic when used for that purpose. The intravenous administration of placebo substances is to be criticized since untoward effects sometimes are observed. The type of placebo chosen by the physician depends not only on the situation presented by the patient but on the physician himself and the inescapable patient-doctor relationship or temperamental rapport. As noted by Houston,21 the doctor himself is an important therapeutic agent. It is hard for a doctor to avoid being part actor no matter how he may try. In times past doctors grew beards and wrote prescriptions in Latin, using the apothecary system. This awed a credulous populace and covered some of the gaps in medical knowledge. As we progress it becomes less necessary to resort to this sort of thing. But without carrying it to the point of ,[UNE,
1954
charlatanism the doctor is more or less effective by his demeanor, whether this is called personality, bedside manner or anything else, and by the way he does and should modify this for each and every patient in order to establish rapport. Whereas the quiet executive is impressed by quiet efficiency, the folksy farmer’s wife might respond only to a warmer, more personal touch. Essentially, there should be provided an atmosphere in which the patient will be receptive to therapy so that the psychotherapeutic aspect of specific medication is not lost and the psychotherapeutic effect of placebo medication is enhanced. Substances which may be harmful or toxic should never be used as placebos. Because of the wide choice of harmless placebos it is unnecessary to court danger. Inorganic arsenical compounds such as Fowler’s solution by mouth or cacodylates by needle have dwindling indications, if indeed indications still remain at all. Physicians formerly believed firmly in their inherent therapeutic value but with more accurate knowledge of pharmacology this belief has been shaken. There is certainly no specific benefit to be anticipated from the administration of inorganic arsenical preparations. They are described as “alteratives” in our older books of materia medica. This is defined as an “obsolete term originally used for drugs said to reestablish healthy functions of the system.“g Some dermatologists continue to use Fowler’s solution in the treatment of recalcitrant dermatoses, clairning occasionally dramatic improvement, without knowing the modus operandi. But we should no longer use these potentially toxic compounds in a confused way as a sort of impure placebo. It is desirable in patients who respond well (0 placebo therapy to prevent their becoming dependent on placebos. These individuals, considered as a group, are more dependent than most people. The use of placebos supplies a socially acceptable substitute dependency when more profound psychotherapy is not available. Consequently these patients are frequently content to take placebos almost indefinitely. II placebo administration is prolonged, dependent) becomes physiologic, as well as psychologic, as illustrated by characteristic withdrawal phenomena when a placebo narcotic-substitute is discontinued. Since, as already noted, dependency on placebos is undoubtedly less undesirahle than addiction to narcotics, there is justification for their prolonged administration in some cases. But in addition to the question of the propriety
Ethics and Practice of Placebo Therapy-Leslie of allowing a patient to become dependent on the placebo there is always the question of the feasibility of maintaining him satisfactorily on a placebo regimen. This must be resolved on an individual basis and requires careful evaluation and perhaps a period of trial. When the decision has been reached to discontinue placebo medication, the procedure to be employed depends on the relationship of doctor and patient. The patient’s dependency is divided between the doctor and the placebo doctor-symbol. If the former predominates, the problem is relatively simple; if the latter predominates, the difficulty may be very great. The technic employed must be adapted to the specific situation. One warning is in order. The doctor who gives a placebo should never allow himself to appear hostile to a patient at the proposed time of discontinuing it by triumphantly telling him that he wasn’t getting anything but water, lactose or whatever the substance might have been. The man who has used a wheelchair and is being encouraged to walk would fall flat if not given crutches or a cane for support. Similarly, the patient who has leaned on a placebo must not have this support rudely knocked out from under him without some transitional device. Some individuals may be told, if circumstances warrant their being given this information, that they had received placebos to help them away from narcotics or sedatives. Others should never be told that their precious medicine was a hoax. No rule of preselection of patients can be laid down; each doctor treats each patient in his own most effective way. CONCLUDING
REMARKS
In our discussion we have attempted first to establish that the use of the placebo entails the use of deception, then that this deception is permissible since it is for the benefit of the patient. We have defined placebo as “a medicine or preparation which has no inherent pertinent pharmacologic activity but which is effective only by virtue of the factor of suggestion attendant upon its administration.” Placebos are useful in diagnosis, therapy and research. When a placebo is indicated as principal or associated psychotherapy it should not be withheld, but the physician must be alert to the limitations of this form of therapy. The specific technic is largely a matter of personal choice, depending on the physician’s rapport with the patient. The physician should be
sensitive to changes in his patient which would point to a change in or discontinuation of such therapy. The principles set forth are not intended as inviolate rules but only as guides to be modified according to the needs of the individual patient as appraised by the individual physician. The proper use of the placebo requires, in addition to broad medical knowledge, a depth of human understanding not requisite to the purely materialistic approach to medicine. REFERENCES 1. 2. 3. 4.
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