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Archives of General Psychiatry April 1965, Vol. 12, pp. 336-345 Copyright 1965, by American Medical Association

Nonblind Placebo Trial

An Exploration of Neurotic Patients' Responses to Placebo When Its Inert Content Is Disclosed

Submitted for publication Aug 24, 1964. The Johns Hopkins University School of Medicine. Assistant Professor of Psychiatry (Dr. Park) and Instructor in Psychiatry (Dr. Covi). Reprint requests to Henry Phipps Psychiatric Clinic, Baltimore, Md 21205 (Dr. Park).

THE PLACEBO effect, that is, the effect obtained when a presumably inert substance is given to normal or diseased individuals, has been the object of many studies in the last decade. A considerable amount of attention has been paid to the psychological factors underlying this effect, and many workers in the field would subscribe to what Gliedman et al 6 write:

"The so-called placebo effect should be looked upon as an epiphenomenon of complicated psychological processes, which are far more important than the disarmingly simple means utilized for its realization."

What is the nature of these processes? Kurlandls states that ". . . the placebo reaction is generally accepted to be a manifestation of suggestion . . ."; in this framework, one common assumption is that the patient should believe he is taking an active drug.22 Throughout the vast literature on the placebo effect there is a consensus on one basic factor which Hampson et al7 state as follows:

The high value which our culture places on pills and medicine may be involved in this phenomenon whereby even inert substances become endowed with physiological potency when they are presented to the patient as therapeutic agents.

Liberman16 has attempted to conceptualize and systematize many factors of the placebo phenomenon following the analysis of communication research by Hovland et al.8 He resolves the placebo effect into three interacting components: (1) the observable doctor-patient therapeutic stimuli; (2) the predispositional factors in the patient; and (3) the internal mediating processes that are fed by the therapeutic stimuli and the predispositional factors.

While the "internal mediating processes" can be probably only the object of theoretical consideration, the "predispositional factors" as well as the "therapeutic stimuli" have been widely studied. Lasagna et al14 have described such "predispositional factors" which distinguish experimental subjects as placebo reactors and placebo nonreactors. Knowles and Lucas 11,12 classified such predispositions as neuroticism and extraversion, while Tibbetts and Hawkings 22 found unelaborated anxiety to play a key role. Knowles and Lucas11 examined some of the situational factors in the patient's "predisposition" and found that if the experimental participants were in groups of three the response was different than when the experimental subjects were isolated.

The observable doctor-patient therapeutic stimuli have been examined in terms of the personal characteristics of the doctors by Uhlenhuth et al23 and in terms of the doctor's behavior by Joyce 10 and by Fisher et al.2

The role of the stimulus, "pill," has also been studied, particularly in terms of side-effects, via the so-called active placebo which Haas et al 6 suggest should be called "fake placebo" (Kaschiertes Placebo). Lipman et al17 have used atropine for this purpose.

We were unable to find mention in the literature of any experiment testing the assumption that a prerequisite for the placebo effect in a neurotic patient is unawareness of the real nature of the substance received. We therefore designed and carried out the study reported here, with the hypothesis that patients can be willing to take placebo and can improve despite disclosure of the inert content of the pills.

The study was conducted with adult neurotic outpatients who were clearly not alcoholic or suffering from neurological disorder and who presented signs of anxiety. The number of subjects was limited due to the exploratory nature of this unusual and "paradoxical" experiment in which neurotic outpatients asking for help were requested to take capsules containing no medication. A safeguard was introduced by suggesting to each patient that placebo would be prescribed for one week, after which further treatment could be offered. Obviously, this safeguard was another variable in the study, but it was felt that the possibility was still present of obtaining valid and significant results. The restriction of subjects to neurotics presenting signs of anxiety was based on the findings reported by many authors that symptoms related to subjective feelings of apprehension and helplessness are significantly helped by drugs and placebos.1,5


This study took place from June to August, 1963, in the Outpatient Department of the Henry Phipps Psychiatric Clinic, a service for adolescents and adults who cannot afford private care. The patients selected were 15 newly admitted neurotics ranging in age from 19 to 67 years, but only one patient was above 50 years of age. The mean age of the sample was 35 years. Thirteen patients were female and nine were white.

Each patient was seen twice. The first visit involved a complete evaluation, followed by prescription of placebo; the second visit took place a week later and consisted of two separate interviews aimed at assessing change and making further disposition. Two psychiatrists participated, one as therapist for eight patients and the other for seven patients. Each interview was observed through a one-way screen by one of the psychiatrists, who also recorded the session on tape and interviewed the patient at the end of the second session.

At the initial visit, each patient was evaluated for approximately an hour, following which his case was discussed at the regular intake conference. The patient was then seen again for 15 to 30 minutes, during which time the placebo was introduced. A script was prepared and carefully enacted as follows :

"Mr. Doe, at the intake conference we discussed your problems and your condition, and it was decided to consider further the possibility and the need of treatment for you before we make a final recommendation next week. Meanwhile, we have a week between now and your next appointment, and we would like to do something to give you some relief from your symptoms. Many different kinds of tranquilizers and similar pills have been used for conditions such as yours, and many of them have helped. Many people with your kind of condition have also been helped by what are sometimes called "sugar pills," and we feel that a so-called sugar pill may help you, too. Do you know what a sugar pill is? A sugar pill is a pill with no medicine in it at all. I think this pill will help you as it has helped so many others. Are you willing to try this pill?"

The patient was then given a supply of placebo in the form of pink capsules contained in a small bottle with a label showing the name of the Johns Hopkins Hospital. He was instructed to take the capsules quite regularly, one capsule three times a day at each meal time. He was also asked to discontinue any tranquilizer, antidepressant, or sedative he may have been taking at the time. The importance of keeping the next appointment was stressed, and the patient was asked to return the bottle at that time with any pills left over. The statement that the pills had helped many others was usually repeated again, especially if the patient asked questions concerning the treatment, conveying doubtful attitudes about its possible effectiveness.

The second visit consisted of a brief interview focused on the symptoms present at that time and on any changes noticed since the first visit. The alternate psychiatrist then proceeded to further explore with the patient the changes noticed, tlie opinions and feelings of the patient about the treating doctor and the treatment received, and his desires concerning further treatment.

The following improvement measures were used:

A. Overall Change.—This is measured by a 7 point scale ranging from 7, "very much worse," through 4, "no change," to 1, "very much better," rated by the patient immediately prior to the second visit, in terms of how he had felt during the past week compared to how he felt prior to his initial visit. The rating was also made by the doctor at the end of the second visit.

B. Symptom Checklist.—This is a 65-item modified Hopkins Symptom Checklist." The patient was asked how much the symptoms bothered him in the past week in the categories, "not at all," "a little," "quite a bit," and "extremely," scored from 0 to 3. The patient filled out this checklist at the initial interview just prior to introduction of placebo and again immediately prior to the second visit.

C. Target Symptoms.—To obtain this rating, the treating psychiatrist also filled out a Symptom Checklist on the patient immediately after the initial interview. He was instructed not to infer symptoms but to check a "not elicited" category for any symptoms not actually mentioned by the patient. Target Symptoms were defined at the first interview as any complaint checked as present by both doctor and patient. In order to rate change, these Target Symptoms were then scored from the Symptom Checklist filled out by the patient at the second visit,

D. Pathology.—The treating psychiatrist rated each patient on a scale ranging from 1, "no pathology," through 8, "extreme pathology," at each visit, making this rating on the basis of the patient's illness as compared to experience with other outpatients.

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