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  IN THIS Article
 ::  Abstract
 ::  Introduction
 ::  Psychophysiologi...
 ::  Conclusion
 ::  Acknowledgement
 ::  References

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ARTICLE
Year : 1978  |  Volume : 24  |  Issue : 3  |  Page : 147-157

On placebos, placebo responses and placebo responders- A Review of psychological, psychopharmacological and psychophysiological factors, II- psychopharmacological and psychophysiological factors


Department of Psychological Medicine, K.E.M. Hospital and Seth G. S.Medical College, Bombay 400 012., India

Correspondence Address:
D R Doongaji
Department of Psychological Medicine, K.E.M. Hospital and Seth G. S.Medical College, Bombay 400 012.
India
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PMID: 722611

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 :: Abstract 

This article is in continuation with the previous publication. The article reviews various psychopharmacological factors which determine the ultimate success of therapy, even when the drug administered does not have any specific efficacy in conditions under treatment. The importance of usually ignored variables of the psychophysiological state of an individual undergoing therapy, and its relevance to placebo genesis is discussed.



How to cite this article:
Doongaji D R, Vahia V N, Bharucha M. On placebos, placebo responses and placebo responders- A Review of psychological, psychopharmacological and psychophysiological factors, II- psychopharmacological and psychophysiological factors. J Postgrad Med 1978;24:147-57

How to cite this URL:
Doongaji D R, Vahia V N, Bharucha M. On placebos, placebo responses and placebo responders- A Review of psychological, psychopharmacological and psychophysiological factors, II- psychopharmacological and psychophysiological factors. J Postgrad Med [serial online] 1978 [cited 2014 Apr 19];24:147-57. Available from: http://www.jpgmonline.com/text.asp?1978/24/3/147/42660



 :: Introduction Top


Any attempt to understand the phar­macology of placebo reveals a peculiar paradox. Classical pharmacology studies the effects of an active chemical on the functioning of a living organism. The pharmacological study of placebo usually deals with those effects of an inert sub­stance which are independent of its chemical action. The action of placebo is not restricted to subjective symptoms like pain, dizziness, giddiness etc., but is seen also with various symptoms which have objective parameters. Cleghorn [7] et al studied the effects of placebo on adrenocortical secretions. They observed that injections of placebo can produce a response similar to ACTH i.e., changes in the eosinophil and lymphocyte count, sodium and potassium levels, and 17­ketosteroid excretion.

Most situations involving the adminis­tration of a drug consist of the following variables. [14]

  1. The Drug Itself.
  2. Doctor-patient Relationship. [46]
  3. The Patient.
  4. The Person Administering, and Other Environmental Factors.


1. The Drug Itself

Some of the interacting variables about the drug itself need special consideration. A drug can be administered in a variety of ways to impress the consumer. The drug can be a bland white unattractive tablet, or a pretty coloured capsule. It can be given as a syrup, or as a vile liquid, or it can be administered paren­terally in the form of injections which are impressive but painful . [14]

The potency of placebo effect is evident most dramatically by the side effects pro­duced by its administration. These are as frequent and as unpleasant as those which can occur with pharmacological­ly active drugs. Placebos have been known to mimic the effects of true phar­macological substances. [4],[9],[14],[18],[46] Com­plaints like drowsiness, staggering gait, blurring of vision, urinary frequency, ringing in the ears, dermatitis medica­mentosa, anaphylactic shock and a variety of other side effects are reported in the literature. Lasagna et al [26],[27] showed that dose response relationships, peak effects, cumulative action, and holdover effect; can occur during the course of placebo therapy. Cases of habituation and addic­tion to placebo have also been reported in the literature. [28],[54],[55] However the lethal dose of placebo is as yet unknown.

The following side effects have been reported on administration of placebo. [48]

  1. Depression of CNS-reported in 6.6% of cases.
  2. Headache-reported in 3.1%, of cases.
  3. Stimulation of CNS-reported it 2.9% of cases.
  4. Nausea-reported in 2.8% of cases
  5. Constipation-reported in 2.3% of cases.
  6. Vertigo-reported in 2.0% of cases
  7. Dryness of mouth-reported it 1.5%, of cases.
  8. G.I. distress-reported in 1.4% of cases.
  9. Anorexia-reported in 1.2% of cases.
  10. Remainder-reported in less than 110 of cases.


Other side effects of placebo reported in the literature include. [30]

  1. Blood-Eosinophilia.
  2. Skin-Maculopapular rash, urti­caria, sweating, angioneurotic oedema of lips.
  3. Gastro Instestinal-Anorexia, diar­rhoea, nausea, constipation, dry­ness of mouth, vomiting, epigastric pain, abdominal cramps.
  4. Cardio Vascular System-Palpita­tions, tachycardia, changes in blood pressure.
  5. Liver-Alterations in the bioche­mical values.
  6. C.N.S.-Light headedness, head­ache, sensation of warmth, diffi­culty in concentration, vertigo.
  7. C.N.S. (Depression)-Drowsiness, weakness, fatigue, unsteadiness of gait, heaviness of limbs, mental confusion and motor retardation.
  8. C.N.S. (Stimulation) - Nervous­ness in the day, insomnia, tension, motor restlessness and excitement.


It is therefore clear that the scientific evaluation of any new treatment proce­dure or new drug should include a study of placebo interaction. DuBois [8] once said `Any young neophyte can introduce a new drug. It requires a man of large ex­perience and considerable reputation to destroy an old one'. The statement em­phasises the fact that in a clinical study, before any cure is attributed to a new drug, various variables associated with the treatment procedure (e.g. the effects of hospitalisation, attention by the physician, rest, change in the diet etc.) must all be accounted for.

2. Doctor-Patient Relationship [46]

Patients generally look upon the treat­ing physician as their saviour. This often leads to an unrealistic relationship bet­ween the therapist and the patient. Since the majority of patients develop a `posi­tive transference' relationship, a proper manipulation of such a situation can be the basis for deliberate and effective use of placebo therapy.

In any therapeutic endevour the impli­cation has always been that certain vari­ables in the patient were responsible for any undue complication during therapy. Recent studies have shown that the psy­chology and the social standing of the treating physician may contribute sub­stantially to the treatment effects.

The term `iatroplacebogenesis' [46] is used to describe the study of placebo effects produced by physicians. Iatroplacebo­genesis can be direct or indirect.

(a) Direct iatroplacebogenesis

This is a condition produced by the direct effect of the physician's attitude towards (i) the patient, (ii) the treatment, and (iii) the results of the treatment. [46]

(i) Physician's attitude towards the patient

While studying the clients' reactions to initial interviews, Pollansky and Kounin [37] concluded that the physician's personal interest and not his competence was the main determinant of placebogenesis. The patients' liking for the doctor, the doctor's interest, empathy, sympathy, neutrality or disinterest, hostility or rejection-al. contributed to the results.

The therapist's favourable feelings to the patient were related to the therapist': expectation of improvement. The patient'; emotional attachment to the therapist also influenced the obtained improvement. [13] Interest in the patient also varied with the amount of interest expressed by the patient towards the therapy, and the the­rapist's understanding of the patient's behaviour. [46]

Shapiro stated that psychologists who were interested in their patients or sub­jects were usually more persuasive and elicited better conditioning, learning, higher intelligence scores, and better Rorschach records. [46]

(ii) Physician's attitude towards treatment

The Physician's interest in the treat­ment was found to be associated with the ready acceptance of treatment, decreased number of drop-cuts, and a more success­ful outcome. Various authors have con­cluded that the interest of the therapist was the crucial determinant in the report­ed results of surgery in dogs, gastric acid secretions, metabolic changes, laboratory procedures and galvanic skin responses . [46] It determined the success of psycho­therapy, [34],[52] behaviour therapy [23],[47] psy­chochemotherapy, [46] placebo effects [46] and the successes of shamans and quacks and other indigenous therapies. [48]

A number of studies on psychochemo­therapy, psychotherapy and hypnosis have confirmed the view that the therapist's belief, enthusiasm, commitment, interest, and expectations (either positive or nega­tive) about the treatment were the non­specific determinants in all therapies. [46]

(iii) Attitude towards results of treatment

The interest of the investigator resulted in data distortion not only caused by ran­dom observer effects, but also by inten­tional or unintentional non-random ob­server bias. [46]

In one experiment [43] on rat learning, two sets of investigators were told that their subjects were selectively bred for either high or low levels of intelligence. In actual fact the rats in both groups were geneti­cally similar. The results showed signifi­cantly better learning from rats who were supposed to be of high intelligence (in accordance with the prior instructions given to the investigator).

It was also inferred that the more bias­ed investigators tended to make larger errors in the direction of their precon­ceived notions.

(b) Indirect iatroplacebogenesis

Shapiro has stated that indirect iatro­placebogenesis is a subtle mechanism which is used extensively and which has not been considered adequately in the literature. [46]

Interest in the theory and method of treatment on the part of the treating physician as opposed to personal interest in the patient may also lead to placeboge­nesis. This happened when the patient misinterpreted the physician's interest in his treatment as interest in his person. Placebo effects were also augmented when the physician was prestigious, and dedicated to his theory, [46] and when the therapy was elaborate, detailed, expen­sive, time-consuming, fashionable, esoteric and dangerous.

Iatroplacebogenesis was reported to be particularly important in psychological therapies and situational variables where staff attitudes, type of patient populations, treatment procedures and miscellaneous factors could have influenced the results.

(3) The Patient

In conventional medicine, credit or blame (for undue effectiveness or undue ineffectiveness of therapy) is attributed to variables in the patient. Many of the possible variables in a patient which ulti­mately influence the drug effects have al­ready been discussed. Some of the other variables are as follows:

(a) Personality traits and patterns

Attempts to correlate an individual's personality and placebo effect have not been successful.

Various authors have found multiple dependant variables. Placebo responders have been shown [46] to be compliant, reli­gious, hypochondriac, [44] anxious, less edu­cated, and freqnent users of cathartics. [46] Lasagna, [26],[27] Beecher, [3],[4],[5] Frank, [10] Gleid­man et al, [12] Shapiro [46],[47] and others found that anxious and depresed patients were frequent placebo responders. Dependency, neuroticism, extraversion, etc., were the other variables which were considered to be important. [46]

Shapiro [47] reviewed the available litera­ture on placebo responders and concluded that no specific traits seem to characterise placebo responders. Gordon [14] reinforced Shapiro's statement with his own state­ment that `the relationship between per­sonality traits and placebo reaction that is found in one situation may not appear or may even be reversed in another situa­tion.'

This was very clearly demonstrated in an important study by Knowles and Lucas. [21]

The authors carried out a series of ex­periments under `individual' and `group' conditions. All the subjects were asked to report on the `side effects' of a new 'psy­chotropic drug' which was in fact a small white lactose tablet. Patients assigned at random to `individual' conditions assessed the pill while seated alone in a room; while those assigned to `group' conditions sat in groups of three. All subjects were scored for neuroticism, emotional instabi­lity and extraversion on the Maudsly Per­sonality Questionnaire. [14]

In two experiments carried out under `group' conditions there was a significant­ly positive correlation between neuroti­cism and the number of placebo side effects reported. When similar compari­sons were made in two experiments car­ried out under `individual' conditions, the relationship between neuroticism and side effects was almost zero. This observation confirmed the postulate that under group conditions of drug administration, the more suggestible neurotic was likely to `catch' side effects from other people around him. [14]

In the same experiment, Knowles and Laucast [21] demonstrated a complex relation­ship between extraversion and frequency of side effects to placebo. In one `indivi­dual' experiment, there was a significant correlation between extraversion scores and placebo response. This did not appear in any of the two `group' experiments. In the second `individual' experiment the op­posite results were found and the intro­verted subjects showed more placebo effects. The reason given for this was that in the first `individual' as well as `group' experiments, student nurses were used as subjects, whereas the second `individual' experiment was done with theological students. The experimenters suggested that the theological students, having little background knowledge of drugs, reported minor effects which were disregarded by the more experienced nurses. Introverts would be much more meticulous in doing so, and hence the greater placebo response in these personalities.

Thus no significant correlationship exists between personality patterns and traits and placebo effect, except that an­xious people respond better to placebo.

(b) Nature of placebo stimulus

It is a common experience that various individuals respond differently to placebos given in different forms, e.g., patients from lower socioeconomic strata generally pre­fer injections, whereas patients from higher strata respond better to a stimulus given in the form of a psychotherapeutic sitting. [14] The size of the tablet, absence or presence of sugar coating, rigidity of in­structions at the time of administration etc., all contribute to placebogenesis. [46] Such variables are poorly understood at present and in the opinion of Shapiro, these factors probably explain the dis­crepancies found in the results in various studies. [46]

(c) Age, Sex, Intelligence

Various studies which tried to correlate age, sex and intelligence with the placebo response gave contradictory results.

In an animal study, untreated rats plac­ed in cages with amphetamine treated rats, essentially mirrored the behaviour of the treated animals. [33] Other investiga­tors have found that when a therapeutic procedure was administered in a permis­sive atmosphere where communication be­tween patients and the doctor was encour­aged, the improvement was greater than when the same procedure was performed under nonpermissive conditions where silence was maintained. [32] When stimulant and depressant drugs were given in vari­ous combinations to subjects who were paired off with interpersonal contact per­mitted during the response period, a sub­ject's response on psychomotor tests was dependent not so much on the drug he received as upon the drug his partner received. [32]

(4) Persons Administering and Other Environmental Factors

(a) Staff attitudes

The attitudes of the staff, their expect­ations anad their conflicts can influence placebo reactions. [46] The reported incid­ence of placebogenesis in one study decreased from 70% to 25% when the nurses' attitude towards the administered placebo was conveyed to the patients. [56] In another study, patients on placebo show­ed greater improvement than those on tranquilizers. The authors of this study [2] attributed their results to the unfavour­able attitude of the nurses towards phar­macoiherapy.

It has been postulated by some [29],[40],[46] that the reasons for the continued decrease of patients from mental asylums since 1955 was not only because of the in­troduction of major tranquilizers, but also due to changes in the character of atten­dants, better nursing, greater understand­ing of the cases by physicians, increase in the number of staff members, greater op­timism, and so on. It is difficult to per­ceive why such a phenomenon should have occurred at this particular period in time.

Changes associated with research acti­vity have been reported to produce im­provement in 80% of patients. [39] Multiple studies have concluded that research, while attempting to control some vari­ables, often introduced other variables which were often overlooked by the ex­perimenters.[19],[31],[39],[46]

(c) Subjects

Most of the drug studies reported in the literature used volunteers as control groups, and all [27],[36],[38] except one study [41] had concluded that the basic assumption that volunteers constituted a `normal' group was untenable, as they had a high incidence of social or psychological patho­logy. The degree of normality or abnor­mality appeared to depend on the population studied. [36],[38],[41]

(d) Treatment procedures

Patients did not react uniformly to different treatment procedures. Several investigators have reported that 50% of patients do not take their medication or follow instructions about dosages. [11]

It is probable that prescribing exactly nine drops of liquid medication would be more effective than the conventional ten drops, [14],[46] and greater placebo effect was observed with injections, various compli­cated procedures and impressive machi­nes. [46] It was also reported that chronic psychotic patients when transferred from mental asylums to intensive care units, showed marked improvement in their symptoms even before the proposed lobo­tomy was performed. [46]

Psychiatric Clinical Diagnosis and Placebo Responses

Symptoms of anxiety and depression are known to respond to placebo more often than other symptoms seen in various psychiatric illnesses.

It has often been reported that overt, manifest free floating anxiety predisposes to a placebo response, [3],[9],[10],[12],[22],[26],[46] as stress and anxiety lead to an increased response to suggestion. This asumption has been disproved by the simple observa­tion that patients with hysteria who are supposed to be very suggestible, but who have no manifest anxiety are poor placebo reactors. [46]

Illnesses which are not associated with significant manifest anxiety e.g., person­ality disorders, conversion and dissociative hysterical reactions etc., generally show a lesser incidence of placebogenesis. Pre­sence of anxiety, tension, restlessness, and panic are often considered favourable for ultimate improvement. Anxiety is also a favourable prognostic sign in many other therapies like psychotherapy, psychophar­macotherapy, insulin treatment and lobotomy. [46]

Samuels and Edisen [45] in their study of 100 psychotics and neurotics (in-patients and out-patients) showed that 10% of the cases responded negatively to `placebo treatment' 25% showed no response, 29% showed mild improvement, 29% showed moderate improvement, whereas marked improvement was seen in 7% of cases.

Various studies are reported in the literature where attempts were made to correlate placebogenesis with some psy­chiatric symptoms. Placebo effects were frequently reported in patients with symp­toms of anxiety and depression [14],[46] Han­koff et al [15] Kurland [24],[25] and Samuels [45] found no relation between placebo effect and a given diagnostic category. Shapiro [42] however found a definitely higher inten­sity and range of such placebo responses in psychotics.

Constancy and type of placebo effects

In the opinion of many workers like Fisher, [9] Hargreaves, [16] Rashkis, [39] Roberts [42] Samuels, [45] Shapiro [46] etc., severity or duration of symptoms of an illness did not directly correlate with the response to placebo. However, Black' in his study has shown that a short duration of illness was more likely to elicit a posi­tive placebo effect. [53] Even the duration of time during which a placebo effect lasts is disputed. There are reports suggesting that the placebo response is short lived [6] though some authorities oppose such a views. [3],[10]

Many authors have reported that patients who showed positive placebo responses were also likely to show a more pronounced and quicker improvement in the underlying illness.

Some authors have pointed out incon­sistency in placebo reactors. Various studies usually report a greater incidence of positive as compared to negative re­actors. [15],[46] It has also been shown that patients may not show placebo responses in one study but may respond to a place­bo in another situation. [46],[57] This pheno­menon supports the opinion of some authorities that the placebo response is seldom uniform, constant or pre­dictable. [24],[25],[46]

Miscellaneous Factors

Factors like spontaneous remissions, chance emergence of short term symp­toms, changes in social structure, changes in the environment etc. are also likely to predispose to placebogenesis. [46]




 :: Psychophysiological factors Top


A close psychophysiological supervision may help to distinguish those effects which are truly produced by an active drug from those produced from the ex­plicit or implicit response predisposition on the part of the subject, [50] and/or the experiment. [44] The phenomenon of place­bogenesis has two facets; it is observed that just as a 'drug effect' may be pro­duced when no drug is administered, on some occasions `no drug effect' may occur when an adequate dose of an active drug is administered. [51] Phychophysiological studies on placebos are of two types. [51]

  1. Base line studies in which the sub­ject is studied in a basal state e.g.study of the G.S.R. in a normal relaxed subject. [51]
  2. Reactive studies in which the sub­ject is given a stimulus e.g. a drug or a learning task, or a situation that leads to anxiety, hate, guilt etc. [51]


Implicit and explicit responses need to be considered in any experimental situation. [51] In either treatment situation viz, drug or placebo, implicit sets or expectations exist e.g., an anxious subject change; even a basal study into a reactive one whereas an experienced habitual volunteer changes a typically reactive study into a basal study. [51] Such effects can be separated in a clinical study by repeated monitoring of physiological parameters Placebo effects tend to become complicated when other factors like drug conditioning are introduced into the experimental design. Beecher [5] found that the average effectiveness of placebo in relieving pathological pain (tissue pathology) was 35% while the effectiveness of placebo on experimentally induced pain e.g., by using tourniquet, heat etc. was only 3.2%. This difference in effectiveness was to be attributable to the placebo being more effective in the presence of anxiety and apprehension, which often accompanied pathological pain as opposed to pain in experimentally induced situations.

Sternbach [49] studied the role of explicit responses. In his study he gave three sets of instructions to three groups of subjects He instructed the subjects that one kind of pill would relax the stomach, that the second was a placebo pill, and that the third pill was a stimulant to the stomach The three pills were plastic coated magnets which helped to record the G.I. tract ­ activity. In four out of six cases the activity of the gastro-intestinal system was found to vary with the experimental suggestions.

Lasagna et al [26] have emphasised the subjects participating in drug trials shout be initially studied to assess their predisposition to implicit and explicit responses.

According to Stroebel [51] a drug can be defined `as an externally supplied, solid, liquid or gaseous substance that is eaten, injected into, inhaled or absorbed by a living organism.' Such substances may be biologically viable (bacteria, viruses etc.) and may or may not result in any notice­able change in behaviour or physiological functioning. Drug effects may be direct or idirect (primary or secondary) depending on whether a response change was specifi­cally attributable to the substance itself or whether the presence of the substance altered the role of other agents in exerting its effect. Thus, in addition to agents usu­ally defined as drugs, such as aspirin, adrenalin or digitalis, the usual respira­tory gases, and any contaminants they may contain, foods, beverages and even inert substances such as carbon granules in the atmosphere which may or may not be radioactive must be included.'

Such a broad definition obviously changes any study on psychophysiology into a study of drug effects, as many vari­ables such as diet, smoking, alcohol con­sumption etc., are not carefully controlled. Some of the other factors that need to be controlled are room temperature, humi­dity etc. Smoking causes a peculiar pro­blem since rigid control on frequency of smoking is itself likely to provoke anxiety in a heavy smoker.

One also finds multiple reports in the literature of studies on schizophrenic pati­ents where an act of omission in control­ling various constituents of their diet led to erroneous conclusions regarding physio­logical changes occurring in schizophrenia or about the effectiveness of a drug in this condition. [1],[17],[20],[57]

It is then obvious that a close psycho­physiological supervision is most essential before any therapeutic benefit can be at-tributed to a pharmacologically active sub­stance or any other treatment modality, as various environmental and dietetic variables alter the psychophysiological activity of an individual to a significant extent. To add to this, a placebo can also produce physiological changes simulating drug effect.

Thus, in the absence of recognised phy­siological changes that can be attributed to a placebo effect or inability to predict a placebo responder by ascertaining his psy­chophysiological activity before a study is undertaken, the mere knowledge of an individual's psychophysiological status does not help an experimenter in confirm­ing or predicting the presence, absence, or probability of placebogenesis.


 :: Conclusion Top


To conclude, the whole subject of place­bogenesis can be summarised in the words of Pepper [35] who wrote that 'The giving of placebo-when, how and what seems to be a function of the physician, which like certain of the functions of the body, is not to be mentioned in polite society'.


 :: Acknowledgement Top


The authors thank Dr. C. K. Deshpande, Dean, K.E.M. Hospital & G.S. Medical College, for the permission to publish this paper.

 
 :: References Top

1.Asatoor, A. M. Levi, A. J. and Milne, M. D.: Tranylcynromine and Cheese. Lancet, 2: 733-734, 1963.  Back to cited text no. 1    
2.Baker, A. A. and Thorpe, J. G.: Placebo response. Am. Med. Assn. Arch. Neurol. Psychiat, 78: 57-60, 1957.  Back to cited text no. 2    
3.Beecher, H. K.: Measurement of the subjective responses, New York Oxford University Press, 1959. Cited by Shapiro, A. K.: 'The Placebo Response' in Modern Perspectives in World Psychiatry. 2, Edited by John Howells. 1st edition. pp. 596-613. Oliver & Boyd-Edinburgh & London, 1968.  Back to cited text no. 3    
4.Beecher, H. K.: Nonspecific forces sur­rounding disease and treatment. Jour. of Amer. Med. Assn. 179: 437-440, 1962.  Back to cited text no. 4    
5.Beecher H. K.: Qualification of the sub­jective pain experience. In, "Psychopatho­logy of perception," 1965.  Back to cited text no. 5    
6.Black, A. A.: Factors predisposing to a placebo response in new out-patients with anxiety states. Brit. J. Psychiat., 112: 557­567, 1966.  Back to cited text no. 6    
7.Cleghorn, R. A., Graham, B. F., Camp­bell, R. B., Rublee, N. K., Elliot, F. H. and Saffran, M.: Anxiety states, their re­sponse to ACTH and to isotonic saline. In proceedings of the first clinical ACTII conf. Philadelphia Blakston (1950). Cited by Wolf, S.: in Pharmacology of Placebos. Pharmacology Review 11: 689-703, 1959.  Back to cited text no. 7    
8.Du Bois, E. F.: Elimination of worthless drugs. Trans. Ass. Am. Physician, 54, 1, (1939). Cited by Wolf,57: Pharmacology of Placebos. Pharmae. Rev., 11: 689-703, 1959.  Back to cited text no. 8    
9.Fisher . H. K. and Olin, B. M.: The dynamics of placebo therapy-A clinical study. Am. J. Med. Sci., 232: 504-512, 1956.  Back to cited text no. 9    
10.Frank, J. D.: Persuasion and Healing, Baltimore. The John Hopkins Press, 1961. Cited by Shapiro, A. K.: The Placebo Response' in Modern Perspectives in World Psychiatry. 2, Edited by John Howells. 1st edition. pp. 596-613. Oliver & Boyd-Edinburgh & London, 1968.  Back to cited text no. 10    
11.Garetz, F. K.: A comparison of urine phenothiazine test results with prescribed medication dosage. Am. J. Psychiat, 118: 1133-1134, 1962.  Back to cited text no. 11    
12.Gleidman, C. H., Nash, E. H., Imber, S. D., Stone, A. R. and Frank, J. D.: Reduction of symptoms by pharmacologi­cally inert substances and by short term psychotherapy. Am. Med. Assn. Arch. Neurol. Psychiat- 79: 345-351, 1958.  Back to cited text no. 12    
13.Goldstein, A. P.: Therapist patient ex­pectancies in psychotherapy. New York: Mac Millan Ltd., 1962. Cited by Shapiro, A. K..: 'The Placebo Response' in Modern Perspectives in World Psychiatry. 2, Edited by John Howells. 1st edi­tion, pp. 596-613. Oliver & Boyd­Edinburgh & London, 1968.  Back to cited text no. 13    
14.Gordon, C.: When is a Drug not a Drug? in Drugs and Human Behaviour. Allen Lane, The Penguine Press, London, Chap. 2, p. 24-50, 1970.  Back to cited text no. 14    
15.Hankoff, L. D., Engelhardt, D. M. and Preedman, N.: Placebo Response in schizophrenic out-patients. Arch. Gen . Psychiat, 2: 33-42, 1960.  Back to cited text no. 15    
16.Hargreaves, G. R., Hamilton, M. and Roberts, J. M.: Treatment of anxiety states. II clinical trial of benactyzine in anxiety states. J. Ment. Sci. , 104: 1056­1061, 1958.  Back to cited text no. 16    
17.Hedberg, D. L. Gordon, M. W. and Glueck, B. C.: Six cases of hypertensive crisis in patients on tranylcypromine after eating chicken livers. Am. J. Psych., 122: 933-937, 1966.  Back to cited text no. 17    
18.Honigfeldt, G.: Nonspecific factors in treatment. Dis. Ner. Syst., 25: 145-156. 1964.  Back to cited text no. 18    
19.Houston W. R.: Doctor himself as therapeutic agent. Ann. Int. Med. 11: 1416-1425, 1938.  Back to cited text no. 19    
20.Kety, S. S.: Biochemical theories of schizophrenia-International Jour. of Psy­chiatry. 1, 409-446, 1965.  Back to cited text no. 20    
21.Knowles, J. B. and Lucas. C. J.: Experi­mental studies of the placebo response. J Ment. Sci. 106: 231-240, 1960.  Back to cited text no. 21    
22.Kornetsky, C. and Humphries, 0.: Rela­tionship between effects of a number of centrally acting drugs and personality. Am. Med. Assoc, Arch. Neur. Psych. 77: 325-327, 1957.  Back to cited text no. 22    
23.Krasner, L.: Social and professional im­plications of behaviour therapies. Paper presented at the first international con­gress on social psychiatry, London, 1964. Cited by Shapiro, A. K. `The Placebo Re­sponse' in Modern prospectives in World Psychiatry. 2: pp. 596-613. Edited by Howells John Co. 1st edition. Oliver & Boyd-Edinburgh & London, pp. 597, 1968.  Back to cited text no. 23    
24.Kurlands, A. A.: The drug placebo-its psychodynamic and conditional reflex ac­tion. Behav. Sci. 2: 101-110, 1957.  Back to cited text no. 24    
25.Kurland, A. A.: The placebo in, "Progress in psychotherapy," Vol. III Eds. Masser­man, J. H. & Moreno, J. L., New York Grime and Stratton, 1958. Cited by Shapiro, A. K.: `The Placebo Response' in Modern Perspectives in World Psychiatry. 2, Edited by John Howells. 1st edition. pp. 596-613. Oliver & Boyd-Edinburgh & London, 1968.  Back to cited text no. 25    
26.Lasagna, L., Mosteller, F,, Von Felsinger, J. M. and Beecher, H. K.: A study of placebo response. Am. J. Med. 16: 770-779, 1954.  Back to cited text no. 26    
27.Lasagna, L. and Von Felsinger, J. M.: The volunteer subject in research. Science. 120: 359-361, 1954.  Back to cited text no. 27    
28.Leslie, A.: Ethics of practice of placebo therapy. Amer. J. Med. 16: 854-862, 1954.  Back to cited text no. 28    
29.Linn, E. L.: Sources of uncertainty in studies of drugs affecting mood, menta­tion or activity. Am. J. Psychiat., 116: 97-103, 1959.  Back to cited text no. 29    
30.Meyler, L. and Herxheimer, A.: Side effects of Drugs 7, William & William Company, Baltimore, 1972, p. 691.  Back to cited text no. 30    
31.Mezaros, A. F. and Galigher, D. L.: Measuring indirect effect of treatment on chronic wards. Dis. Nerv. Syst., 19: 1­10, 1958.  Back to cited text no. 31    
32.Nakaro, Shigeuki et al.: An experi­mental study of the placebo response. Journal of Japanese Psychosomatic So­ciety., 12 (3): 186-192, 1972.  Back to cited text no. 32    
33.Nash, Michael: Expectations of Drug Effect Questionnaire (unpublished instru­ment).  Back to cited text no. 33    
34.Parloff, M. B. and Robinstein, E. A.: Summary of research problems in psy­chotherapy conference, 1958. In, "Re­search in Psychotherapy." Eds. Rubin­stein, E. A. and Parloff, M. B. Washing­ton, American Phychological Association, 1958. Cited by Shapiro, A. K.: `The Placebo Response' in Modern Perspec­tives in World Psychiatry. 2, Edited by John Howells. 1st edition, Oliver & Boyd -Edinburgh & London, 1968, pp. 596-613.  Back to cited text no. 34    
35.Pepper, O. H. P.: A note on placebo. Amer. J. Pharma., 117: 409-412, 1945.  Back to cited text no. 35    
36.Perlin, S., Pollin, W. and Butler, R. N.: The experimental subject. Am. Med. Assn. Arch. Neurol. Psychiat. , 80: 65-70, 1958.  Back to cited text no. 36    
37.Polansky, N. and Kounin, J.: The clients' reactions to initial interviews. Hum. Rel., 9: 237, 1956. Cited by Shapiro, A. K.: `The Placebo Response' in Modern Perspectives in World Psychiatry, 2, Edited by John Howells. 1st edition, Oliver & Boyd­Edinburgh & London, 1968, pp. 596-613.  Back to cited text no. 37    
38.Pollin, W. and Perlin, S.: Psychiatric evaluation of "Normal control" Volun­teers. Am. J. Psychiat., 115: 129-133, 1958.  Back to cited text no. 38    
39.Rashkis, H. A. and Smarr, E. R.: Psy­chopharmaco-therapeutic. A triadistic approach. Am. Med. Assoc. Arch. Neurol. Psychiat., 77: 202-209, 1957.  Back to cited text no. 39    
40.Rathod, N. H.: Tranquilisers and patients environment. Lancet, is 611-613, 1958.  Back to cited text no. 40    
41.Richards, T. W.: Personality of subjects who volunteer for research on a drug. J. Proj. Tech., 24: 424-429, 1960.  Back to cited text no. 41    
42.Roberts, J. M. and Hamilton, M.: Treat­ment of anxiety states. J. Ment. Sci., 104: 1052-1055, 1958.  Back to cited text no. 42    
43.Rosenthal, R.: On the social psychology of the psychological experimental results. Am. Sci. 51: 268. 1963. Cited by Shapiro, A. K.: `The Placebo Response' in Modern Perspectives in World Psychiatry. 2, Edit­ed by Howells John, 1st edition, Oliver & Boyd-Edinburgh & London, 1968, pp. 593­613.  Back to cited text no. 43    
44.Rosenthal, R.: Experimenter, out-come orientation and the results of the psycho­logical experiments. Psychological Bulle­tin, 61, 40'5, 1965. Cited by Shapiro, A. K.: 'The Placebo Response' in Modern Per­spectives in World Psychiatry. 2, Edited by Howells John, 1st edition, Oliver & Boyd-Edinburgh & London, 1968, pp. 593­613.  Back to cited text no. 44    
45.Samuels Arthurs and Edisen, C. B.: Study of Psychiatric effects of placebo. J. of Louisiana M. Soc., 113: 114-117, 1961. In, "Year book of Psych. Neuro. Neurosurg", 61-62, 1931, p. 384.  Back to cited text no. 45    
46.Shapiro, A. K.: 'The Placebo Response' in Modern Perspectives in World Psy­chiatry. 2, Edited by John Howells. 1 st edition, 'Oliver & Boyd-Edinburgh & Lon­don, 1968, pp. 596-613.  Back to cited text no. 46    
47.Shapiro, A. K.: The Behaviour Therapies: Therapeutic Break through a latent Fads? Am. J. Psy. 132: 154-159, 1976.  Back to cited text no. 47    
48.Meyler, L.: Sick effects reported with placebos, in side effects of Drugs, Vol. 6, p. 517, Eds. L. Meyler; Al Herxheimer. Williams & Williams Company, Baltimore, 1968.  Back to cited text no. 48    
49.Sternbach, R. A.: The effects of instruc­tional sets on autonomic responsibility. Psychophysiology, 1: 67-72, 1964.  Back to cited text no. 49    
50.Sternback, R. A.: Principals of psycho­physiology, New York. Academic, 1966. Cited by Strupp, H. H.: Psychotherapists in action. Grime & Stratton, New York, 1960.  Back to cited text no. 50    
51.Stroebel, C. F.: Psychophysiological phar­macology. In, "Hand book of psychophy­siology," Chapter 20, pp. 787-938, Edited by Greenfield, N. S. and Sterbach, R. A., New York, Holt, Rinehart and Winston Inc., 1972.  Back to cited text no. 51    
52.Strupp, H. H.: Psychotherapists in action. Gr5ne & Stratton, New York, 1960. Cited by Shapiro, A. K.: 'The Placebo Res­ponse' in Modern Perspectives in World Psychiatry. 2, Edited by John Howells. 1st edition, Oliver & Boyd-Edinburgh & London, 1968, pp. 596-613.  Back to cited text no. 52    
53.Tibbets, R. W. and Hawkins, J. R.: The placebo response. J. Ment. Sci. 102: 60-66, 1956.  Back to cited text no. 53    
54.Tyler, D. B.: The effect of Amphetamine sulphate and some barbiturates on the fatigue produced by prolonged wakeful­ness. Am. J. Physiol., 150: 253-262, 1947.  Back to cited text no. 54    
55.Vicar, 0.: Dependence on placebo-a case report. Brit. J. Psy., 115: 1189 1190, 1969.  Back to cited text no. 55    
56.Volgyesi, F. A-: "School for patients" Hypnosis therapy and psychoprophylaxis. Brit. Jr. Med. Hypnotism., 5: 8-12, 1954.  Back to cited text no. 56    
57.Wolf, S.: Pharmacology of Placebos. Pharmae Rev., 11: 689-703, 1959.  Back to cited text no. 57    




 

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