Psychopharmacology
Psychopharmacology 57, 253- 261 (1978)
9 by Springer-Verlag 1978
Situational Factors Contributing to the Placebo Effect* Steven L. Gryll 1'** and Martin Katahn 2 1 Waterbury Hospital, U.S.A. 2 Vanderbilt University,U.S.A,
Abstract. The influence of four variables (status of
communicator of drug effects, attitude of dentist, attitude of dental technician, and message of drug effects) on the obtainment of placebo effects in an oral surgery clinic was investigated. Dependent variables were (1) rating of pain experienced from mandibularblock injection, (2) pre-post placebo state anxiety, and (3) pre-postplacebo fear of injection. Enthusiastic messages of drug effects produced statistically and clinically significant reductions in postplacebo fear of injection and state anxiety and markedly lower ratings of pain experienced during injection of local anesthetic. Although there was a strong tendency for positive placebo effects to occur when the dental staff was perceived as friendly and supportive, only the attitude factors obtained statistical significance. The status of the communicator accounted for very small portions of the variance. Key words: P l a c e b o Anxiety
S i t u a t i o n a l factors -
Pain -
In the past 20 years there has been growing interest in ascertaining factors associated with and potentiating placebo effects in pharmacological research. The earlierst investigations of the placebo effects (e.g., von Felsinger et al., 1955 ; Lasagna et al., 1954; Rashkis and Smarr, 1957) were primarily concerned with attempting to differentiate subjects in pharmacological research projects into categories on the basis of their responses to placebo administration. In these studies individuals exhibiting positive, negative, or equivocal responses * This investigation was conductedin the Oral Surgery Clinic of Ben Taub General Hospital, Houston, Texas ** Address for offprint requests: StevenL. Gryll, Ph.D., Merriman Hall, Team II, Waterbury Hospital Health Center, Waterbury, Connecticut 06720, U.S.A.
were designated placebo responders, negative placebo reactors, or placebo nonreactors, respectively. Disappointing results (for review see Honigfeld, 1964; Shapiro, 1971) have caused investigators to abandon this type of investigation, primarily because an individual's response to placebo administration has been shown to vary both within and across drug administration situations (Kurland, 1957; Wolf et al., 1957). A second category of studies investigating the occurrence of the placebo effect is comprised of those projects that have attempted to associate demographic factors and personality attributes with a propensity to respond or not respond to placebo administration. This method of investigating the placebo effect has also proven less fruitful than originally anticipated (Frank, 1973; Honigfeld, 1964; Shapiro et al., 1968; Shapiro, 1971). For example, in some studies age was negatively correlated with placebo effects (Gliedman et al., 1958; Kurland, 1958; Shapiro et al., 1968); in other studies, age was positively correlated with placebo effects (Hankoff et al., 1960; Knowles and Lucas, 1960). In much the same fashion, personality traits have not been shown to correlate consistently with placebo reactivity in different situations (Shapiro, 1971; Shapiro et al., 1968). The unproductiveness of the search for personality attributes and demographic characteristics that distinguish the placebo reactor and non-reactor has led several theorists, most notably Frank (1973) and Shapiro (1971), to suggest that placebo reactivity is primarily situationally determined. Both Frank and Shapiro consider the drug recipient's heightened level of anxiety in a drug-taking situation and the r01e and actions of the physician as two of the primary situational determinants of the placebo effect. Although both of these theorists perceive the individual's heightened level of anxiety in a drug-taking situation as the catalyst potentiating the individual's response to a placebo, Frank and Shapiro suggest that the heightened anxiety operates in a different way to create a placebo effect.
0033-3158/78/0057/0253/$1.80
254 Frank primarily views the patient's heightened anxiety as a stimulus for the mobilization by the physician of the patient's (1) faith in the medical profession in general, (2) faith in his personal physician's competence in particular, and (3) hope that he, the patient, will get well. The mythological status typically attributed to physicians by members of Western cultures is an integral component of Frank's formulation of factors determining the placebo effect. A patient seeking a physician's aid expects to be helped by the physician (therapist's myth, Ehrenwald, 1966). The physician also believes that, in most instances, his knowledge and actions will benefit the patient (personal myth, Frank, 1973). Frank suggests that the principal means by which the physician's personal myth is conveyed to the patient is through communication of the physician's expectations of the pharmacological effects of the prescribed medication. The physician's expectations then serve to help activate the patient's hopes of getting well and his faith in the physician. Shapiro (1971, 1964a, b, c, 1968) also emphasizes the importance of the role of the physician as a major determinant of the placebo effect. While he recognizes the import of the patient's anxiety, faith in the physician, and expectation and anticipation of relief, Shapiro feels that not enough attention has been given to the ways in which physicians themselves contribute to the placebo effect. He has coined the term iatroplacebogenesis, or the study of placebo effects produced by physicians, to aid in his conceptualization of the placebo effect. Shapiro (1971, 1968, 1964a, b) has suggested that iatroplacebogenesis can manifest itself in two forms. Direct iatroplacebogenesis refers to placebo effects produced by the physician's attitudes toward his patients, toward their treatment, or toward the results being obtained with a specific therapeutic intervention. He feels that a physician's interest in his prescribed treatment program or in the obtainment of positive results with that treatment may be perceived by his patients as interest in themselves rather than in the treatment or the results of the treatment. In other words, a physician's warm, enthusiastic attitudes toward the treatment may be displaced by the patients onto themselves and perceived by the 9 patient as indicating that (1) the physician likes them, and (2) the physician is confident he will be able to alleviate the patient's discomforts. When coupled with the potential for positive transference to the physician and the high credibility and status typically enjoyed by physicians, the concept of direct iatroplacebogenesis provides a very useful way of conceptualizing the respective roles of physician and patient vis-a-vis drug administration. An interested individual of mythical proportions (physician) conveys messages, implicitly or explicitly, of reassurance, social approval, and expecta-
Psychopharmacology57 (1978) tions of hope to an individual (patient) experiencing stress and anxiety because of his clinical condition. Shapiro (1971, 1964 a, b) further suggests that iatroplacebogenesis can manifest itself in a more subtle, indirect fashion. This occurs when by virtue of the physician's interest in a particular phenomenon or treatment modality, he interacts with the patient in a manner unlike that in which he normally would and dissimilar from the patient's prior experiences with physicians. That is, a treatment ostensibly intended for the patient has an indirect effect on the patient because the direct effect is actually focused on the physician. Unlike direct iatroplacebogenesis, indirect iatroplacebogenesis occurs when the physician is unaware that he is interacting with patients in an atypical manner. As in the case of direct iatroplacebogenesis, the patient perceives the interaction as connoting interest in him rather than interest in the treatment itself. Shapiro (1960, 1963, 1971) suggests that indirect iatroplacebogenesis may account for the initial successes of many therapies (e. g., insulin coma therapy, certain chemotherapeutic agents) that have later met with less positive outcomes. For example, the danger inherent in insulin coma therapy may cause the physician to assess more carefully the treatment's usefulness for patients. When coupled with the dangerous and, to the layman, seemingly esoteric aspects of the treatment itself, the physician may interact with the patient undergoing this therapy in an atypical manner. This may result in the physician being perceived by the patient as very concerned and personally involved with the patient rather than professionally disinterested, as would be his normal behavior with patients. This change in the physician, through indirect iatroplacebogenesis, may possibly result in the patient perceiving the physician as being interested in him and his feeling better, leading to a positive placebo effect. In a recent review of the research on factors underlying the occurrence of the placebo effect, Gryll (1973) suggested that the physician's implicitly (unintentional, covert, and primarily nonverbal) and explicitly (overt, intentional, and primarily verbal) communicated messages of his expectations of a drug's effectiveness may provide a useful vehicle for operationalizing several of the principal determinants of the placebo effect enumerated by Frank (1973) and Shapiro (1971). On the one hand, implicit and explicit sets of expectations enable both the physician and patient to share basic assumptions concerning the etiology of symptoms and the most effective and efficient ways of alleviating them. In this way the patient's hope and faith in the physician and the treatmentmodalitymay be mobilized. On the other hand, the physician's implicitly and explicitly communicated messages of drug effects provide the communication channels through which direct
S. L. Gryll and M. Katahn: SituationalFactors and the Placebo Effect and indirect iatroplacebogenesis may occur. Through these sets of physician's expectations the physician is able to display interest and concern toward the treatment, which in turn may be displaced by the patient onto himself. There appears to be ample evidence that a physician's attitude about chemotherapy can affect the usefulness of the drug. Patient improvement under chemotherapeutic intervention, as measured by both patient and physician ratings of improvement, is enhanced when the physician prescribing the medication anticipates that the medication will be useful in ameliorating patient discomfort (Feldman, 1956; Haefner et al., 1960; Hanlon et al., 1960; Klett and Lasky, 1962; Sabshin and Ramot, 1956; Sheard, 1963). There is also strong support for the hypothesis that the modification of subject's or patient's responses to drugs can be accomplished by explicit communications of expectations of drug effects by pharmacological investigators or physicians (Luparello et al., 1968, 1970; Lyerly et al., 1964; McFadden et al., 1969; Park and Covi, 1965; Penick and Fisher, 1965; Schacter and Singer, 1962; Sternbach, 1964; Strupp et al., 1973; Uhlenhuth and Park, 1964; Weiss et al., 1970; Wolf and Pinsky, 1954). The generality of the influence of these types of communications is enhanced by the fact that they have altered the reactions of individuals to drugs within several different response modalities. For example, Sternbach (1964) demonstrated that explicit instructional sets could modify the frequency of occurrence of an autonomic event (gaslLric motility); Park and Covi (1968) demonstrated that explicit communications of physician's expectations of drug effects were capable of engendering patient improvement as measured by symptom rating scales and anxiety measures; and Schachter and Singer (1962) demonstrated that explicit information from the investigator that an administered drug produces specific symptoms affects the self-reports of those symptoms by subjects receiving that information. Another important factor in the obtainment of placebo effects is the quality of the interaction between patient and physician. Uhlenhuth and his colleagues (1959, 1964, 1966), Shapiro et al. (1954), and Atoynatan et al. (1954) have found that warm, enthusiastic interactions between physicians and patients tend to promote placebo effects, while more neutral and less enthusiastic interactions between physicians and patients tend to reduce the incidence of placebo effects. One of the principal methodological problems with the studies attempting to determine the importance of the relationship of the physician and patient to the obtainment of placebo effects is that the physician's implicit or explicit message of drug effectiveness was always confounded with a particular type of relationship
255
(warm or cold). For example, in Uhlenhuth et al. (1966) physicians projecting a warm, enthusiastic demeanor toward patients and drug always explicitly communicated positive expectations of drug effectiveness. Physicians projecting a less enthusiastic nature toward patients and medication always explicitly communicated somewhat equivocal expectations of drug effectiveness. To eliminate this confusion it is necessary to present different types of explicit messages of drug effectiveness within each of the potential physicianpatient interaction patterns. The prevailing opinion is that placebo effects appear to be potentiated by situational factors (Frank, 1973; Gryll, 1973; Shapiro, 1971). The next step in investigating the placebo effect would appear to be isolating various situational aspects of clinical environments in an attempt to determine their relative importance in increasing or decreasing the likelihood of the occurrence of placebo effects. Three situational factors have been considered important contributors to the obtainment of placebo effects: (1) the high status position of physicians (Frank, 1973; Shapiro, 1971), (2) the type of information included in the message to patients of anticipated drug effects (Gryll, 1973), and (3) the quality of interaction existing between the patient and those individuals providing clinical care (Shapiro et al., 1973). The quality-of-interaction variable must include some assessment by the patient of the professional staff's attitudes toward him. An 'interactionist' would speculate that placebo effects would be more likely to occur when (1) the patient perceives the professional staff as being warm and supportive, (2) a high status person delivers a very positive message concerning his expectations of a drug's effects, and (3) that message conveys very positive expectations of drug effectiveness. It is less clear what the anticipated outcome would be if any of these three factors were varied. The present study attempts to shed some light on this issue by factorially investigating them in a clinical situation.
Materials and Methods
Subjects. The subjects were 160 individuals coming to the Oral Surgery Clinicof Ben Taub General Hospital, Houston, Texas. All subjectswerevolunteersat least18 yearsof age. Fifty-threepercentof the subjectswere males and the mean age of the subject population was 33 years.Severalclinicalconsiderationsservedas parametersfor the inclusionof subjectsin this study: (1) eachsubjectparticipatingin the investigation needed to receive a local anesthetic, xylocaine hydrochloride, in order to complete necessary dental procedures (extractions); (2) only subjects needing injectionsanesthetizingthe lingualnerve(amandibularblock) wereused; (3) this visitmust have been their first to the Oral Surgery Clinicin the past six months. All patientswereinformedprior to investigationthat theymay be a participantin psychologicalresearchin accordancewith standards set by the Research on Human Subjects at Vanderbilt University.
256 They were asked to complete several rating scales. They were further informed that participation in research would in no way moderate their care from staff.
Experimental Design. The design is a 2 x 2 x 2 x 4 factorial with the following independent variables: (1) status of the individual deliverin'g the communication of tile effects of the pill administration to the patient (i.e. dentist or dental technican); (2) the attitude of the dentist toward the patient (i.e., warm or neutral); (3) the attitude of the dental technician toward the patient (i.e., warm or neutral); and (4) type of message given to the patient concerning the anticipated effects of the pill (i.e., oversell, undersell, saliva, no pill).
Social Interaction Manipulation. The amount and type of verbal interaction among the dentist, dental technician, and patient depended on the patient's assigned interaction condition. Whenever the dentist or dental technician was assigned to play a ~warm' role, he or she attempted to encourage verbal interaction. In these instances the dentist or dental technician attempted to be as friendly as possible toward the patient. Whenever the dentist or dental technician was assigned to play a 'neutral' role, he or she attempted to minimize verbal interaction. There would be more personal interaction and a greater exchange of niceties (e. g., "It's such a nice day !") intended to put the patient at ease in the warm condition than in the neutral condition. There were four dentists, all males, and two dental technicians, both females, who participated. Pill Administration Messages. There were three pill-administrationmessage conditions and one condition in which patients did not receive a pill. In all instances the pill used was a placebo. The placebo was a 100-mg, light green spansule capsule. Half of the patients were informed of the anticipated effects of the pill administration procedure by the dentist and half of the subjects were informed of the anticipated effects of the procedure by the dental technician. The three types of messages of expected effects of the pill administration are presented below: 1. Oversell: "This is a recently developed pill that I've found to be very effectNe in reducing tension, anxiety, and sensitivity to pain. It cannot harm you in any way. The pill becomes effective almost immediately." 2. Undersell: "This is a recently developed pill that reduces tension, anxiety, and sensitivity to pain in some people. Other people receive no benefit at all from it. I personally have not found it to be very effective. It cannot harm you in any way. The pill becomes effective almost immediately if it's going to have an effect." 3. Saliva: "This is a recently developed pill that reduces the amount of saliva in your mouth. It cannot harm you in any way. The pill becomes effective almost immediately." Dependent Variables. Three dependent variables were used in this study: (1) the patient's rating of pain experienced from injection of local anesthesia; (2) the patient's pre- and postplacebo rating of his fear of receiving an injection of local anesthesia; and (3) a pre- and postplacebo measure of the patient's lavel of state of anxiety (StateTrait Spielberger et al., 1969). These three variables were selected because they provide some insight into some of the patient's perceptions of the forthcoming dental procedures. The state-anxiety questionnaire provided an assessment of the patient's apprehension at two points in the procedure. The fear-of-injection item and the injection-pain rating provided an assessment from two different perspectives of one of the more anxiety-arousing parts of the entire dental procedure.
Procedure. Upon entering the waiting room of the dental clinic each potential participant in this investigation was asked to complete a state-anxiety rating scale. In addition to this scale, each individual was asked to rate two items: (1) a seven-point scale assessing their degree of fear of receiving an injection of a local anesthetic, with 1 signifying no fear of injection and 7 signifying terror of injection; and
Psychopharmacology 57 (1978)
Table 1. Analysis of variance of patients' ratings of pain experienced during injection of local anesthesia Source
df
MS
F
~o Variance
Status (A) Attitude of dentist (B) Attitude of dental technician (C) Message (D) AxB AxC AxD BxC BxD CxD AxB• A x Bx D AxCxD BxCxD AxB• C• D
1
2.500
3.76
1.13
1
3.600
5.41"
1.62
1 3 1 1 3 1 3 3 1 3 3 3 3
4.900 26.12 0.100 0.100 1.883 0.900 0,250 2,550 0.400 1.850 0.183 6.517 2.050
7.36** 39.24***
2.21 35.31 0.05 0.05 2.55 0.41 0.34 3.45 0.18 2.50 0.25 8.81 2.77
2.83*
3.83* 2,78* 9.79*** 3.08*
* P < 0.05 ** P < 0.01 *** P < 0.001
(2) how comfortable (nonanxiety producing) they found lhe waiting room to be. The dental examination proceeded until a determination had been made concerning whether a mandibular-block injection was necessary to accomplish diminished responsivity to pain. If a particular patient did not require local anesthesia at that neutral site, he was eliminated from participation in the study. Three of the four groups of patients requiring mandibular-block injections were asked to ingest the placebo. Depending on their experimental condition, they received one of the messages specified earlier concerning the anticipated effects of the pill. This message was delivered by either the dentist or the dental technician. All four groups of patients once again completed that anxiety scale and the fear-of-injection item. The item dealing with the patient's feelings about the waiting room was deleted from this testing period. At this point all of the patients received mandibular-block injections. One minute after the injection they were asked to rate the amount of pain they felt from the injection. The pain rating was a fivepoint sematic differential, with 1 signifying no pain from injection and 5 signifying agonizing pain from injection. In addition to completing the pain-rating scale, patients were asked to rate the behavior of both the dentist and the dental technician. This rating assessed the effectiveness of the operationalization of the interaction variable. Both of the ratings of the behavior of dentists and dental technicians were four-point sematic differentials, with 1 signifying very unfriendly behavior and 4 signifying very friendly behavior.
Results A 2 x 2 x 2 x 4 (Status x Attitude of Dentist x Attitude of Dental Technician • Message) analysis of variance of patient's ratings of pain experienced from the injection of local anesthesia yielded several statistically s i g n i f i c a n t f i n d i n g s ( T a b l e 1): (1) A t t i t u d e o f D e n t i s t (F(1,128) = 5.4 P < 0 . 0 5 ) ; (2) A t t i t u d e o f D e n t a l
S. L. Gryll and M. Katahn: Situational Factors and the Placebo Effect
257 Table
Dentist
2. Means and standard deviations of patients' pain ratings
Dental Technician
D gives message
=,4
9
",l=--
/
_za
/',,,..,._7i
21
I
I
I
Dw
~ /- Aj ' * . / ~LI - ' - / ~ ~..
A
I
i
I
Oversell
.]"
Undersell
.X" v .g .~ X s
I
Dw
Dw
Dn
Dn
Dw
Dw
Dn
Dn
DTw
DTn
DTw
DTn
DTw
DTn
DTw
DTn
Saliva No Pill
ATTITUDE LEVEL Saliva , ~ No pill e ~ - -
Oversell ~. Undersell o,
Dn
DT w
DT.
DT w
DT.
1.60 0.55 2.60 0.55 4.20 0.84 2.40 1.14
1.80 0.45 3.80 0.84 3.20 0,45 4.60 0.55
1.60 0.55 3.00 1.00 4.00 0.71 4.20 0.45
2.00 0.0 3.00 1.00 4.20 0.45 4.20 1.10
DT gives message
Fig. 1. Rating of pain experienced during injection Ow
/ 50-
/
>tu4
/
e
I..- ~
Oversell Undersell Saliva
X
z
0.24, P < 0.01; d > 0.24, P < 0.01), respectively). A 2 x 2 x 2 x 4 analysis of variance indicated no statistically significant difference among the patients on how comfortable they felt in the waiting room. In each case the intended operationalization of 'friendliness' of the dental staff was consonant with the patient's perceptions of these individuals. That is, the operationalization of the dentists' and dental technicians' 'friendliness' was 100 ~ effective. A further series of analyses investigated whether any of the dentists, dental technicians, or combinations of dentist and dental technician differentially affected patient's responses on the three dependent variables. The results of
s. L. Grylland M. Katahn: SituationalFactors and the Placebo Effect the series of 2 x 4 (Dentist x Dental Technician) analyses of variance indicated that none of the dependent measures (pain ratings, post-placebo state anxiety, or post-placebo fear of injection) was affected significantly by any of the dentists, dental technicians, or combinations of dentist and dental technician.
Discussion
The results of the present study indicated that placebo effects are at least partially determined by variations in situational aspects of clinical procedure. Each of the four independent variables investigated (the status of the placebo administrator, the attitude of the dentists and dental technicians toward the patient, and the type of message about expected drug effects) affected the patients' responses to placebo administration. The most salient of the four variables was the type of information contained in the message of drug effects. As anticipated, patients in the Oversell message condition exhibited the least pain from the injection and significantlypost-placebo reductions in both state anxiety and fear of injection. The only other occurrence of a Message condition producing a positive placebo effect was the reduction of state anxiety exhibited by patients receiving the Undersell message. These data argue rather strongly for paying close attention to what information patients are given about the effects of drugs. The same information in terms of statements about potential reductions in anxiety,tension, and sensitivityto pain was contained in both the Oversell and Undersell messages; it is the drug administrator's enthusiasm, faith, attitudes, and expectations of the drug that varied. These data appear to indicate that patients were sensitive to this difference in the two messages and that this sensitivity translated itself into significantly different patterns for the two Message conditions. Because the No Pill message condition was expected to serve as a methodological control group, the significant interactions involving the No Pill message condition were not anticipated, However, since dentists and dental technicians were aware that a placebo study was being conducted, this knowledge may have covertly affected their behavior when they interacted with patients in the No Pill condition, and thus be an instance of indirect iatroplacebogenesis. This possibility illustrates the importance of specifying the amount of information about the effects of the drug both the patient and clinic personnel have. Although the complexity of some of the interactions obtained on the pain-rating variable approaches inexplicability, it is very clear that explicit messages of drug effects are potent determinants of patient's responses to
259
drug administration. The other three situational variables investigated (the attitude of the dentist, the attitude of the dental technician, and the status of the communicator of drug effects) all contribute in much more subtle fashion to the obtainment of placebo effects. Replication will be required to assess more accurately the consequence of variations in these three situational factors. The variations in the attitude of dentist and dental technician and the status of the drug administrator did not significantly influence the patients' responses to the state-anxiety questionnaire or the fear-of-injection item. These two variables did affect pain-rating responses. The lower pain ratings of patients in the DwDT w attitude condition suggests that when clinic personnel create a warm, friendly environment for their patients, the patients' perceptions of one of the more unpleasant aspects of dental procedure (i. e., injections of local anesthesia) can be moderated. These results agree with and extend previous findings (Atoynatan et al., 1954: Shapiro et al., 1954; Uhlenhuth et al., 1959, 1964, 1966) that a physician's warm, supportive attitudes can potentiate the occurrence of placebo effects. Unlike the previous studies containing message-social interaction confounds, the present investigation independently explored the influence of the affective environment and message of placebo effect. Independent of Message condition, either a warm dentist or a warm dental technician can potentiate positive placebo effects. The lack of a significant main effect of status of the drug administrator is noteworthy since it was anticipated that the high-status communicattor of drug effects would be associated with a greater production of positive placebo effects than the low-status communicator of drug effects. Indeed, although the main effect of Status approached statistical significane on only the pain-rating measure, the lower-status communicator appears to be associated with lower pain ratings than the high-status communicator. The importance of the Status variable emerged only within the interplay among the four situational variables under investigation. It had been anticipated that the four independent variables would interact significantly on each of the three dependent measures. This was not the case. significant third-order interaction occurred only on the patients' ratings of pain experienced from the injection of local anesthesia. An interesting finding and one of the primary contributiors to the significant Status x Attitude of Dentist x Attitude of Dental Technician x Message interaction was the markedly lower pain ratings obtained when the dental technician rather than the dentist gave the Undersell message in the DwDTn attitude condition. This was a difference of 1.6 points. A possible explanation of this finding is that patients
260
perceive a warm dentist giving an Undersell message as a dissonance-arousing experience. That is, the patients may perceive the Undersell message and the dentist's warmth as incongruous, which may result in their reducing their expectations of the dentist's competence and credibility. Perhaps a more plausible explanation is that the warm dentist is able to create a more supportive environment for his patients. This supportive environment possibly results in patients responding to a greater degree to the dentist's statement that he has not found the drug to be of much clinical usefulness. Both explanations of this interaction support Gryll's (1973) suggestion that implicit and explicit communications of drug effects promote positive placebo effects through the creation of the therapist myth, and subsequent existential shift and doctrinal compliance (Ehrenwald, 1966), and direct and indirect iatroplacebogenesis 1. A dissonance-arousing communication (warm dentist giving Undersell message) possibly reduces the likelihood that dentist and patient can share an assumptive world (accomplishing an existential shift) concerning the dentist's competence and judgment. This inability to effect an existential shift would prevent doctrinal compliance, in this instance positive placebo effeccts, from occurring. The second explanation suggests that patients may anticipate the effects of the drug to be negligible because of the communication to that effect from a warm dentist. In this instance the equivocal message of drug effects may reduce the possibility that direct or indirect iatroplacebogenesis might occur by creating for the patient a more ambiguous relationship with his dentist. From this perspective there would be no treatment from which the patients would displace the dentist's interest onto themselves. Situational aspects comprising the clinical environment appear to be a fruitful area of research into the nature of placebo effects. The results of the present study illustrate the influence of implicit and explicit communications of drug effects on the obtainment of placebo effects. A productive area of inquiry appears to be the exploration of the meaning to the patient of different messages in different attitude conditions. The information gathered in such an inquiry would greatly increase knowledge of how patients perceive drug administrations and what aspects of the process are of particular salience of them. 1 A clinical example served to illustrate this phenomenon. In 1973 a 42-year-old woman required morphine and intravenous injection of valium prior to extraction of first and second upper molars. She was randomly assigned to the DwDTw-Oversell condition with the dentist delivering the message of drug effects. When the dentist returned to give her the postplacebo forms, he found her 'almost asleep and very relaxed' (her words)
Psychopharmacology 57 (1978) References
Atoynatan, T. H., Goldstone, S., Goldsmith, J., Cohen, L. D.: The differential effects of carbon dioxide and nitrous oxide inhalation therapies upon anxiety symptoms under permissive and nonpermissive conditions. Psychiatr. Q. 28, 641-649 (1954) Ehrenwald, J. : Psychotherapy: myth and method: an integrated approach. New York: Grune and Stratton 1966 Feldman, P. E. : The personal element in psychiatric research. Am. J. Psychiatry 113, 5 2 - 54 (1956) Frank, J. J. D.: Persuasion and healing: a comparative study of psychotherapy. Baltimore: Johns Hopkins 1973 Gryll, S. L.: Implicit sets, explicit sets and the placebo effect. Unpublished manuscript, Vanderbilt University 1973 Gliedman, L. H., Gantt, H., Teitelbaum, G. C. : Some implications of conditional reflex studies for placebo research. Am. J. Psychiatry 113, 1103-1107 (1957) Haefner, D. P., Sacks, J. M., Mason, A. S. : Physicians' attitudes towards chemotherapy as a factor in psychiatric patients' responses to medication. J. Nerv. Ment. Dis. 131, 64-69 (1960) Hankoff, L. D., Freedman, N., Engelhardt, D. M. : Placebo responses in schizophrenic outpatients. Arch. Gen. Psychiatry 2, 33 (1960) Hanlon, T. E., Weiner, G., Kurland, A. A. :The psychiatric physician and the phenothiazine tranquilizers. J. Nerv. Merit. Dis. 130, 67-71 (1960) Honigfeld, G. : Non-specific factors in treatment: review of socialpsychological factors. Dis. Nerv. Syst. 25, 225-239 (1964) Klett, C. J., Lasky, J. J. : Attitudes of hospital staff members towards mental illness and chemotherapy. Dis. Nerv. Syst. 23, 101 - 106 (1962) Knowles, J. B., Lucas, C. J.: Experimental studies of the placebo response. J. Ment. Sci. 106, 231 (1960) Kurland, A. A. : The drug placebo - its psychodynamic and conditional reflex action. Behav. Sci. 2, 101-110 (1957) Lasagna, L., Mosteller, F., von Felsinger, J. M., Beecher, H. K. : A study of placebo response. Am. J. Med. 16, 770 (1954) Luparello, T., Leist, N., Lourie, C. H., Sweet, P. : The interaction of psychologic stimuli and pharmacologic agents on airway reactivity in asthmatic subjects. Psychosom. Med. 32, 509-513 (1970) Luparello, T., Lyons, H. A., Bleecker, E. R., McFadden, G. R., Jr.: Influence of suggestion on airway reactivity in asthmatic subjects. Psychosom. Med. 30, 819-825 (1968) Lyerly, S. B., Ross, S., Krugman, A. D., Clyde, D. J. : Drugs and placebos: the effects of instructions upon performance and mood under amphetamine sulfate and chloral hydrate. J. Abnorm. Soc. Psychol. 68, 321-327 (1964) McFadden, G. R., Jr., Luparello, T., Lyons, H. A., Bleecker, E. : The mechanism of action of suggestion in the induction of acute asthmatic attacks. Psychosom. Med. 31, 134-143 Park, L. C., Covi, L. : Non-blind placebo trial: an exploration of neurotic patients' responses to placebo when its inert content is disclosed. Arch. Gen. Psychiatry 12, 336-345 (1965) Penick, S. B., Fisher, S.: Drug-set interaction: psychological and physiological effects of epinephrine under differential expectations. Psychosom. Med. 27, 177-182 (1965) Rashkis, H. A., Smarr, E. R. : Drug and milieu effect with chronic schizophrenics. A. M. A. Arch. Neurol. Psychiatry 77, 202 (1957) Sabshin, M., Ramot, J.: Psychotherapeutic evaluation and the psychiatric setting. A. M. A. Arch. Neurol. Psychiatry 75, 362--370 (1956) Schacter, S., Singer, J. E.: Cognitive, social, and physiological determinants of emotion state. Psychol. Rev. 69, 379-399 (1962) Shapiro, A. K. : A contribution to the history of the placebo effect. Behav. Sci. 5, 109-135 (1960)
S. L. Gryll and M. Katahn: Situational Factors and the Placebo Effect Shapiro, A. K. : The psychological use of medication. In: The psychological basis of medical practice',, H. U Lief, V. F. Lief, and N. R. Lief, eds. New York: Harper 1963 Shapiro, A. K. : Placebogenics and iatroplacebogenics. Med. Times 92, 1037-1043 (1964a) Shapiro, A. K. : Etiological factors in the placebo effect. J. A. M. A. 187, 712-714 (1964b) Shapiro, A. K. : The placebo response. In: Modern perspectives in world psychiatry, J. G. Howels, ed. Edinburgh: Oliver and Boyd 1968 Shapiro, A. K., Wilensky, H., Struening, E. L. : Study of the placebo effect with a placebo test. Comp. Psychiatry 9, 118 (1968) Shapiro, A. K. : Placebo effects in medicine, psychotherapy, and psychoanalysis. In: Bergin, A. E., and Garfield, S. L. (Eds.), Handbook of psychotherapy and behavior change: an empirical analysis, A. E. Bergin and S. L. Garfield, eds. New York: John Wiley and Sons 1971 Shapiro, A. P., Myers, T., Reiser, M. F., Ferris, E. B. : Comparison of blood pressure response to veriloid and doctor. Psychosom. Med. 16, 478-487 (1954) Sheard, M. H. : The influence of doctor's attitude on the patient's responses to antidepressant medication. J. Nerv. Ment. Dis. 136, 555- 560 (1963) Spielberger, C. D., Gorsuch, R. L., Lushene, R. E. : The state-trait anxiety inventory. Palo Alto, California: Consulting Psychologists Press 1968 Sternbach, R. A.: The effect of instructional sets on autonomic responsivity. Psychophysiology 1, 67-72 (1964)
261 Strupp, H. H., Levenson, R. W., Manuck, S., Snell, J., Hinrichsen, J. J., Boyd, S. : Influence of suggestions and pharmacologic drug effects on total respiratory resistance in mild asthmatics. Paper presented at meeting of American Psychosomatic Society, Denver (1973) Uhlenhuth, E. H., Canter, A., Neustadt, J. O., Payson, H. P.: The symptomatic retief of anxiety with meprobamate, phenobarbitol, and placebo. Am. J. Psychiatry 115, 905-910 (1959) Uhlenhuth, E. H., Park, L. C.: The influence of medication (imipramine) and doctor in relieving depressed psychoneurotic outpatients. J. Psychiatr. Res. 2, 101-122 (1964) Uhlenhuth, E. H., Rickels, K., Fisher, S., Park, L. C., Lipman, R. S., Mock, J. : Drug, doctor's verbal attitude and clinic setting in the symptomatic response to pharmacology. Psychopharmacologia (Berl.) 9, 392-417 (1966) Von Felsinger, J. M., Lasagna, L. Beecher, H. K. : Drug-induced mood changes in man. II. Personality and reactions to drugs. J. A. M. A. 157, 1113 (1955) Weiss, J. H., Martin, C., Riley, J. : Effects of suggestion on respiration in asthmatic children. Psychosom. Med. 32, 409-415 (1970) Winer, B. J. : Statistical principles in experimental design. New York: McGraw-Hill 1971 Wolf, S., Doering, C. R., Clark, M. L., Hagans, J. A. : Chance distribution and the placebo reactor. J. Lab. Clin. Med. 49, 37 (1957)
Received September 26, 1977
Psychopharmacology 57, 253- 261 (1978)
9 by Springer-Verlag 1978
Situational Factors Contributing to the Placebo Effect* Steven L. Gryll 1'** and Martin Katahn 2 1 Waterbury Hospital, U.S.A. 2 Vanderbilt University,U.S.A,
Abstract. The influence of four variables (status of
communicator of drug effects, attitude of dentist, attitude of dental technician, and message of drug effects) on the obtainment of placebo effects in an oral surgery clinic was investigated. Dependent variables were (1) rating of pain experienced from mandibularblock injection, (2) pre-post placebo state anxiety, and (3) pre-postplacebo fear of injection. Enthusiastic messages of drug effects produced statistically and clinically significant reductions in postplacebo fear of injection and state anxiety and markedly lower ratings of pain experienced during injection of local anesthetic. Although there was a strong tendency for positive placebo effects to occur when the dental staff was perceived as friendly and supportive, only the attitude factors obtained statistical significance. The status of the communicator accounted for very small portions of the variance. Key words: P l a c e b o Anxiety
S i t u a t i o n a l factors -
Pain -
In the past 20 years there has been growing interest in ascertaining factors associated with and potentiating placebo effects in pharmacological research. The earlierst investigations of the placebo effects (e.g., von Felsinger et al., 1955 ; Lasagna et al., 1954; Rashkis and Smarr, 1957) were primarily concerned with attempting to differentiate subjects in pharmacological research projects into categories on the basis of their responses to placebo administration. In these studies individuals exhibiting positive, negative, or equivocal responses * This investigation was conductedin the Oral Surgery Clinic of Ben Taub General Hospital, Houston, Texas ** Address for offprint requests: StevenL. Gryll, Ph.D., Merriman Hall, Team II, Waterbury Hospital Health Center, Waterbury, Connecticut 06720, U.S.A.
were designated placebo responders, negative placebo reactors, or placebo nonreactors, respectively. Disappointing results (for review see Honigfeld, 1964; Shapiro, 1971) have caused investigators to abandon this type of investigation, primarily because an individual's response to placebo administration has been shown to vary both within and across drug administration situations (Kurland, 1957; Wolf et al., 1957). A second category of studies investigating the occurrence of the placebo effect is comprised of those projects that have attempted to associate demographic factors and personality attributes with a propensity to respond or not respond to placebo administration. This method of investigating the placebo effect has also proven less fruitful than originally anticipated (Frank, 1973; Honigfeld, 1964; Shapiro et al., 1968; Shapiro, 1971). For example, in some studies age was negatively correlated with placebo effects (Gliedman et al., 1958; Kurland, 1958; Shapiro et al., 1968); in other studies, age was positively correlated with placebo effects (Hankoff et al., 1960; Knowles and Lucas, 1960). In much the same fashion, personality traits have not been shown to correlate consistently with placebo reactivity in different situations (Shapiro, 1971; Shapiro et al., 1968). The unproductiveness of the search for personality attributes and demographic characteristics that distinguish the placebo reactor and non-reactor has led several theorists, most notably Frank (1973) and Shapiro (1971), to suggest that placebo reactivity is primarily situationally determined. Both Frank and Shapiro consider the drug recipient's heightened level of anxiety in a drug-taking situation and the r01e and actions of the physician as two of the primary situational determinants of the placebo effect. Although both of these theorists perceive the individual's heightened level of anxiety in a drug-taking situation as the catalyst potentiating the individual's response to a placebo, Frank and Shapiro suggest that the heightened anxiety operates in a different way to create a placebo effect.
0033-3158/78/0057/0253/$1.80
254 Frank primarily views the patient's heightened anxiety as a stimulus for the mobilization by the physician of the patient's (1) faith in the medical profession in general, (2) faith in his personal physician's competence in particular, and (3) hope that he, the patient, will get well. The mythological status typically attributed to physicians by members of Western cultures is an integral component of Frank's formulation of factors determining the placebo effect. A patient seeking a physician's aid expects to be helped by the physician (therapist's myth, Ehrenwald, 1966). The physician also believes that, in most instances, his knowledge and actions will benefit the patient (personal myth, Frank, 1973). Frank suggests that the principal means by which the physician's personal myth is conveyed to the patient is through communication of the physician's expectations of the pharmacological effects of the prescribed medication. The physician's expectations then serve to help activate the patient's hopes of getting well and his faith in the physician. Shapiro (1971, 1964a, b, c, 1968) also emphasizes the importance of the role of the physician as a major determinant of the placebo effect. While he recognizes the import of the patient's anxiety, faith in the physician, and expectation and anticipation of relief, Shapiro feels that not enough attention has been given to the ways in which physicians themselves contribute to the placebo effect. He has coined the term iatroplacebogenesis, or the study of placebo effects produced by physicians, to aid in his conceptualization of the placebo effect. Shapiro (1971, 1968, 1964a, b) has suggested that iatroplacebogenesis can manifest itself in two forms. Direct iatroplacebogenesis refers to placebo effects produced by the physician's attitudes toward his patients, toward their treatment, or toward the results being obtained with a specific therapeutic intervention. He feels that a physician's interest in his prescribed treatment program or in the obtainment of positive results with that treatment may be perceived by his patients as interest in themselves rather than in the treatment or the results of the treatment. In other words, a physician's warm, enthusiastic attitudes toward the treatment may be displaced by the patients onto themselves and perceived by the 9 patient as indicating that (1) the physician likes them, and (2) the physician is confident he will be able to alleviate the patient's discomforts. When coupled with the potential for positive transference to the physician and the high credibility and status typically enjoyed by physicians, the concept of direct iatroplacebogenesis provides a very useful way of conceptualizing the respective roles of physician and patient vis-a-vis drug administration. An interested individual of mythical proportions (physician) conveys messages, implicitly or explicitly, of reassurance, social approval, and expecta-
Psychopharmacology57 (1978) tions of hope to an individual (patient) experiencing stress and anxiety because of his clinical condition. Shapiro (1971, 1964 a, b) further suggests that iatroplacebogenesis can manifest itself in a more subtle, indirect fashion. This occurs when by virtue of the physician's interest in a particular phenomenon or treatment modality, he interacts with the patient in a manner unlike that in which he normally would and dissimilar from the patient's prior experiences with physicians. That is, a treatment ostensibly intended for the patient has an indirect effect on the patient because the direct effect is actually focused on the physician. Unlike direct iatroplacebogenesis, indirect iatroplacebogenesis occurs when the physician is unaware that he is interacting with patients in an atypical manner. As in the case of direct iatroplacebogenesis, the patient perceives the interaction as connoting interest in him rather than interest in the treatment itself. Shapiro (1960, 1963, 1971) suggests that indirect iatroplacebogenesis may account for the initial successes of many therapies (e. g., insulin coma therapy, certain chemotherapeutic agents) that have later met with less positive outcomes. For example, the danger inherent in insulin coma therapy may cause the physician to assess more carefully the treatment's usefulness for patients. When coupled with the dangerous and, to the layman, seemingly esoteric aspects of the treatment itself, the physician may interact with the patient undergoing this therapy in an atypical manner. This may result in the physician being perceived by the patient as very concerned and personally involved with the patient rather than professionally disinterested, as would be his normal behavior with patients. This change in the physician, through indirect iatroplacebogenesis, may possibly result in the patient perceiving the physician as being interested in him and his feeling better, leading to a positive placebo effect. In a recent review of the research on factors underlying the occurrence of the placebo effect, Gryll (1973) suggested that the physician's implicitly (unintentional, covert, and primarily nonverbal) and explicitly (overt, intentional, and primarily verbal) communicated messages of his expectations of a drug's effectiveness may provide a useful vehicle for operationalizing several of the principal determinants of the placebo effect enumerated by Frank (1973) and Shapiro (1971). On the one hand, implicit and explicit sets of expectations enable both the physician and patient to share basic assumptions concerning the etiology of symptoms and the most effective and efficient ways of alleviating them. In this way the patient's hope and faith in the physician and the treatmentmodalitymay be mobilized. On the other hand, the physician's implicitly and explicitly communicated messages of drug effects provide the communication channels through which direct
S. L. Gryll and M. Katahn: SituationalFactors and the Placebo Effect and indirect iatroplacebogenesis may occur. Through these sets of physician's expectations the physician is able to display interest and concern toward the treatment, which in turn may be displaced by the patient onto himself. There appears to be ample evidence that a physician's attitude about chemotherapy can affect the usefulness of the drug. Patient improvement under chemotherapeutic intervention, as measured by both patient and physician ratings of improvement, is enhanced when the physician prescribing the medication anticipates that the medication will be useful in ameliorating patient discomfort (Feldman, 1956; Haefner et al., 1960; Hanlon et al., 1960; Klett and Lasky, 1962; Sabshin and Ramot, 1956; Sheard, 1963). There is also strong support for the hypothesis that the modification of subject's or patient's responses to drugs can be accomplished by explicit communications of expectations of drug effects by pharmacological investigators or physicians (Luparello et al., 1968, 1970; Lyerly et al., 1964; McFadden et al., 1969; Park and Covi, 1965; Penick and Fisher, 1965; Schacter and Singer, 1962; Sternbach, 1964; Strupp et al., 1973; Uhlenhuth and Park, 1964; Weiss et al., 1970; Wolf and Pinsky, 1954). The generality of the influence of these types of communications is enhanced by the fact that they have altered the reactions of individuals to drugs within several different response modalities. For example, Sternbach (1964) demonstrated that explicit instructional sets could modify the frequency of occurrence of an autonomic event (gaslLric motility); Park and Covi (1968) demonstrated that explicit communications of physician's expectations of drug effects were capable of engendering patient improvement as measured by symptom rating scales and anxiety measures; and Schachter and Singer (1962) demonstrated that explicit information from the investigator that an administered drug produces specific symptoms affects the self-reports of those symptoms by subjects receiving that information. Another important factor in the obtainment of placebo effects is the quality of the interaction between patient and physician. Uhlenhuth and his colleagues (1959, 1964, 1966), Shapiro et al. (1954), and Atoynatan et al. (1954) have found that warm, enthusiastic interactions between physicians and patients tend to promote placebo effects, while more neutral and less enthusiastic interactions between physicians and patients tend to reduce the incidence of placebo effects. One of the principal methodological problems with the studies attempting to determine the importance of the relationship of the physician and patient to the obtainment of placebo effects is that the physician's implicit or explicit message of drug effectiveness was always confounded with a particular type of relationship
255
(warm or cold). For example, in Uhlenhuth et al. (1966) physicians projecting a warm, enthusiastic demeanor toward patients and drug always explicitly communicated positive expectations of drug effectiveness. Physicians projecting a less enthusiastic nature toward patients and medication always explicitly communicated somewhat equivocal expectations of drug effectiveness. To eliminate this confusion it is necessary to present different types of explicit messages of drug effectiveness within each of the potential physicianpatient interaction patterns. The prevailing opinion is that placebo effects appear to be potentiated by situational factors (Frank, 1973; Gryll, 1973; Shapiro, 1971). The next step in investigating the placebo effect would appear to be isolating various situational aspects of clinical environments in an attempt to determine their relative importance in increasing or decreasing the likelihood of the occurrence of placebo effects. Three situational factors have been considered important contributors to the obtainment of placebo effects: (1) the high status position of physicians (Frank, 1973; Shapiro, 1971), (2) the type of information included in the message to patients of anticipated drug effects (Gryll, 1973), and (3) the quality of interaction existing between the patient and those individuals providing clinical care (Shapiro et al., 1973). The quality-of-interaction variable must include some assessment by the patient of the professional staff's attitudes toward him. An 'interactionist' would speculate that placebo effects would be more likely to occur when (1) the patient perceives the professional staff as being warm and supportive, (2) a high status person delivers a very positive message concerning his expectations of a drug's effects, and (3) that message conveys very positive expectations of drug effectiveness. It is less clear what the anticipated outcome would be if any of these three factors were varied. The present study attempts to shed some light on this issue by factorially investigating them in a clinical situation.
Materials and Methods
Subjects. The subjects were 160 individuals coming to the Oral Surgery Clinicof Ben Taub General Hospital, Houston, Texas. All subjectswerevolunteersat least18 yearsof age. Fifty-threepercentof the subjectswere males and the mean age of the subject population was 33 years.Severalclinicalconsiderationsservedas parametersfor the inclusionof subjectsin this study: (1) eachsubjectparticipatingin the investigation needed to receive a local anesthetic, xylocaine hydrochloride, in order to complete necessary dental procedures (extractions); (2) only subjects needing injectionsanesthetizingthe lingualnerve(amandibularblock) wereused; (3) this visitmust have been their first to the Oral Surgery Clinicin the past six months. All patientswereinformedprior to investigationthat theymay be a participantin psychologicalresearchin accordancewith standards set by the Research on Human Subjects at Vanderbilt University.
256 They were asked to complete several rating scales. They were further informed that participation in research would in no way moderate their care from staff.
Experimental Design. The design is a 2 x 2 x 2 x 4 factorial with the following independent variables: (1) status of the individual deliverin'g the communication of tile effects of the pill administration to the patient (i.e. dentist or dental technican); (2) the attitude of the dentist toward the patient (i.e., warm or neutral); (3) the attitude of the dental technician toward the patient (i.e., warm or neutral); and (4) type of message given to the patient concerning the anticipated effects of the pill (i.e., oversell, undersell, saliva, no pill).
Social Interaction Manipulation. The amount and type of verbal interaction among the dentist, dental technician, and patient depended on the patient's assigned interaction condition. Whenever the dentist or dental technician was assigned to play a ~warm' role, he or she attempted to encourage verbal interaction. In these instances the dentist or dental technician attempted to be as friendly as possible toward the patient. Whenever the dentist or dental technician was assigned to play a 'neutral' role, he or she attempted to minimize verbal interaction. There would be more personal interaction and a greater exchange of niceties (e. g., "It's such a nice day !") intended to put the patient at ease in the warm condition than in the neutral condition. There were four dentists, all males, and two dental technicians, both females, who participated. Pill Administration Messages. There were three pill-administrationmessage conditions and one condition in which patients did not receive a pill. In all instances the pill used was a placebo. The placebo was a 100-mg, light green spansule capsule. Half of the patients were informed of the anticipated effects of the pill administration procedure by the dentist and half of the subjects were informed of the anticipated effects of the procedure by the dental technician. The three types of messages of expected effects of the pill administration are presented below: 1. Oversell: "This is a recently developed pill that I've found to be very effectNe in reducing tension, anxiety, and sensitivity to pain. It cannot harm you in any way. The pill becomes effective almost immediately." 2. Undersell: "This is a recently developed pill that reduces tension, anxiety, and sensitivity to pain in some people. Other people receive no benefit at all from it. I personally have not found it to be very effective. It cannot harm you in any way. The pill becomes effective almost immediately if it's going to have an effect." 3. Saliva: "This is a recently developed pill that reduces the amount of saliva in your mouth. It cannot harm you in any way. The pill becomes effective almost immediately." Dependent Variables. Three dependent variables were used in this study: (1) the patient's rating of pain experienced from injection of local anesthesia; (2) the patient's pre- and postplacebo rating of his fear of receiving an injection of local anesthesia; and (3) a pre- and postplacebo measure of the patient's lavel of state of anxiety (StateTrait Spielberger et al., 1969). These three variables were selected because they provide some insight into some of the patient's perceptions of the forthcoming dental procedures. The state-anxiety questionnaire provided an assessment of the patient's apprehension at two points in the procedure. The fear-of-injection item and the injection-pain rating provided an assessment from two different perspectives of one of the more anxiety-arousing parts of the entire dental procedure.
Procedure. Upon entering the waiting room of the dental clinic each potential participant in this investigation was asked to complete a state-anxiety rating scale. In addition to this scale, each individual was asked to rate two items: (1) a seven-point scale assessing their degree of fear of receiving an injection of a local anesthetic, with 1 signifying no fear of injection and 7 signifying terror of injection; and
Psychopharmacology 57 (1978)
Table 1. Analysis of variance of patients' ratings of pain experienced during injection of local anesthesia Source
df
MS
F
~o Variance
Status (A) Attitude of dentist (B) Attitude of dental technician (C) Message (D) AxB AxC AxD BxC BxD CxD AxB• A x Bx D AxCxD BxCxD AxB• C• D
1
2.500
3.76
1.13
1
3.600
5.41"
1.62
1 3 1 1 3 1 3 3 1 3 3 3 3
4.900 26.12 0.100 0.100 1.883 0.900 0,250 2,550 0.400 1.850 0.183 6.517 2.050
7.36** 39.24***
2.21 35.31 0.05 0.05 2.55 0.41 0.34 3.45 0.18 2.50 0.25 8.81 2.77
2.83*
3.83* 2,78* 9.79*** 3.08*
* P < 0.05 ** P < 0.01 *** P < 0.001
(2) how comfortable (nonanxiety producing) they found lhe waiting room to be. The dental examination proceeded until a determination had been made concerning whether a mandibular-block injection was necessary to accomplish diminished responsivity to pain. If a particular patient did not require local anesthesia at that neutral site, he was eliminated from participation in the study. Three of the four groups of patients requiring mandibular-block injections were asked to ingest the placebo. Depending on their experimental condition, they received one of the messages specified earlier concerning the anticipated effects of the pill. This message was delivered by either the dentist or the dental technician. All four groups of patients once again completed that anxiety scale and the fear-of-injection item. The item dealing with the patient's feelings about the waiting room was deleted from this testing period. At this point all of the patients received mandibular-block injections. One minute after the injection they were asked to rate the amount of pain they felt from the injection. The pain rating was a fivepoint sematic differential, with 1 signifying no pain from injection and 5 signifying agonizing pain from injection. In addition to completing the pain-rating scale, patients were asked to rate the behavior of both the dentist and the dental technician. This rating assessed the effectiveness of the operationalization of the interaction variable. Both of the ratings of the behavior of dentists and dental technicians were four-point sematic differentials, with 1 signifying very unfriendly behavior and 4 signifying very friendly behavior.
Results A 2 x 2 x 2 x 4 (Status x Attitude of Dentist x Attitude of Dental Technician • Message) analysis of variance of patient's ratings of pain experienced from the injection of local anesthesia yielded several statistically s i g n i f i c a n t f i n d i n g s ( T a b l e 1): (1) A t t i t u d e o f D e n t i s t (F(1,128) = 5.4 P < 0 . 0 5 ) ; (2) A t t i t u d e o f D e n t a l
S. L. Gryll and M. Katahn: Situational Factors and the Placebo Effect
257 Table
Dentist
2. Means and standard deviations of patients' pain ratings
Dental Technician
D gives message
=,4
9
",l=--
/
_za
/',,,..,._7i
21
I
I
I
Dw
~ /- Aj ' * . / ~LI - ' - / ~ ~..
A
I
i
I
Oversell
.]"
Undersell
.X" v .g .~ X s
I
Dw
Dw
Dn
Dn
Dw
Dw
Dn
Dn
DTw
DTn
DTw
DTn
DTw
DTn
DTw
DTn
Saliva No Pill
ATTITUDE LEVEL Saliva , ~ No pill e ~ - -
Oversell ~. Undersell o,
Dn
DT w
DT.
DT w
DT.
1.60 0.55 2.60 0.55 4.20 0.84 2.40 1.14
1.80 0.45 3.80 0.84 3.20 0,45 4.60 0.55
1.60 0.55 3.00 1.00 4.00 0.71 4.20 0.45
2.00 0.0 3.00 1.00 4.20 0.45 4.20 1.10
DT gives message
Fig. 1. Rating of pain experienced during injection Ow
/ 50-
/
>tu4
/
e
I..- ~
Oversell Undersell Saliva
X
z
0.24, P < 0.01; d > 0.24, P < 0.01), respectively). A 2 x 2 x 2 x 4 analysis of variance indicated no statistically significant difference among the patients on how comfortable they felt in the waiting room. In each case the intended operationalization of 'friendliness' of the dental staff was consonant with the patient's perceptions of these individuals. That is, the operationalization of the dentists' and dental technicians' 'friendliness' was 100 ~ effective. A further series of analyses investigated whether any of the dentists, dental technicians, or combinations of dentist and dental technician differentially affected patient's responses on the three dependent variables. The results of
s. L. Grylland M. Katahn: SituationalFactors and the Placebo Effect the series of 2 x 4 (Dentist x Dental Technician) analyses of variance indicated that none of the dependent measures (pain ratings, post-placebo state anxiety, or post-placebo fear of injection) was affected significantly by any of the dentists, dental technicians, or combinations of dentist and dental technician.
Discussion
The results of the present study indicated that placebo effects are at least partially determined by variations in situational aspects of clinical procedure. Each of the four independent variables investigated (the status of the placebo administrator, the attitude of the dentists and dental technicians toward the patient, and the type of message about expected drug effects) affected the patients' responses to placebo administration. The most salient of the four variables was the type of information contained in the message of drug effects. As anticipated, patients in the Oversell message condition exhibited the least pain from the injection and significantlypost-placebo reductions in both state anxiety and fear of injection. The only other occurrence of a Message condition producing a positive placebo effect was the reduction of state anxiety exhibited by patients receiving the Undersell message. These data argue rather strongly for paying close attention to what information patients are given about the effects of drugs. The same information in terms of statements about potential reductions in anxiety,tension, and sensitivityto pain was contained in both the Oversell and Undersell messages; it is the drug administrator's enthusiasm, faith, attitudes, and expectations of the drug that varied. These data appear to indicate that patients were sensitive to this difference in the two messages and that this sensitivity translated itself into significantly different patterns for the two Message conditions. Because the No Pill message condition was expected to serve as a methodological control group, the significant interactions involving the No Pill message condition were not anticipated, However, since dentists and dental technicians were aware that a placebo study was being conducted, this knowledge may have covertly affected their behavior when they interacted with patients in the No Pill condition, and thus be an instance of indirect iatroplacebogenesis. This possibility illustrates the importance of specifying the amount of information about the effects of the drug both the patient and clinic personnel have. Although the complexity of some of the interactions obtained on the pain-rating variable approaches inexplicability, it is very clear that explicit messages of drug effects are potent determinants of patient's responses to
259
drug administration. The other three situational variables investigated (the attitude of the dentist, the attitude of the dental technician, and the status of the communicator of drug effects) all contribute in much more subtle fashion to the obtainment of placebo effects. Replication will be required to assess more accurately the consequence of variations in these three situational factors. The variations in the attitude of dentist and dental technician and the status of the drug administrator did not significantly influence the patients' responses to the state-anxiety questionnaire or the fear-of-injection item. These two variables did affect pain-rating responses. The lower pain ratings of patients in the DwDT w attitude condition suggests that when clinic personnel create a warm, friendly environment for their patients, the patients' perceptions of one of the more unpleasant aspects of dental procedure (i. e., injections of local anesthesia) can be moderated. These results agree with and extend previous findings (Atoynatan et al., 1954: Shapiro et al., 1954; Uhlenhuth et al., 1959, 1964, 1966) that a physician's warm, supportive attitudes can potentiate the occurrence of placebo effects. Unlike the previous studies containing message-social interaction confounds, the present investigation independently explored the influence of the affective environment and message of placebo effect. Independent of Message condition, either a warm dentist or a warm dental technician can potentiate positive placebo effects. The lack of a significant main effect of status of the drug administrator is noteworthy since it was anticipated that the high-status communicattor of drug effects would be associated with a greater production of positive placebo effects than the low-status communicator of drug effects. Indeed, although the main effect of Status approached statistical significane on only the pain-rating measure, the lower-status communicator appears to be associated with lower pain ratings than the high-status communicator. The importance of the Status variable emerged only within the interplay among the four situational variables under investigation. It had been anticipated that the four independent variables would interact significantly on each of the three dependent measures. This was not the case. significant third-order interaction occurred only on the patients' ratings of pain experienced from the injection of local anesthesia. An interesting finding and one of the primary contributiors to the significant Status x Attitude of Dentist x Attitude of Dental Technician x Message interaction was the markedly lower pain ratings obtained when the dental technician rather than the dentist gave the Undersell message in the DwDTn attitude condition. This was a difference of 1.6 points. A possible explanation of this finding is that patients
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perceive a warm dentist giving an Undersell message as a dissonance-arousing experience. That is, the patients may perceive the Undersell message and the dentist's warmth as incongruous, which may result in their reducing their expectations of the dentist's competence and credibility. Perhaps a more plausible explanation is that the warm dentist is able to create a more supportive environment for his patients. This supportive environment possibly results in patients responding to a greater degree to the dentist's statement that he has not found the drug to be of much clinical usefulness. Both explanations of this interaction support Gryll's (1973) suggestion that implicit and explicit communications of drug effects promote positive placebo effects through the creation of the therapist myth, and subsequent existential shift and doctrinal compliance (Ehrenwald, 1966), and direct and indirect iatroplacebogenesis 1. A dissonance-arousing communication (warm dentist giving Undersell message) possibly reduces the likelihood that dentist and patient can share an assumptive world (accomplishing an existential shift) concerning the dentist's competence and judgment. This inability to effect an existential shift would prevent doctrinal compliance, in this instance positive placebo effeccts, from occurring. The second explanation suggests that patients may anticipate the effects of the drug to be negligible because of the communication to that effect from a warm dentist. In this instance the equivocal message of drug effects may reduce the possibility that direct or indirect iatroplacebogenesis might occur by creating for the patient a more ambiguous relationship with his dentist. From this perspective there would be no treatment from which the patients would displace the dentist's interest onto themselves. Situational aspects comprising the clinical environment appear to be a fruitful area of research into the nature of placebo effects. The results of the present study illustrate the influence of implicit and explicit communications of drug effects on the obtainment of placebo effects. A productive area of inquiry appears to be the exploration of the meaning to the patient of different messages in different attitude conditions. The information gathered in such an inquiry would greatly increase knowledge of how patients perceive drug administrations and what aspects of the process are of particular salience of them. 1 A clinical example served to illustrate this phenomenon. In 1973 a 42-year-old woman required morphine and intravenous injection of valium prior to extraction of first and second upper molars. She was randomly assigned to the DwDTw-Oversell condition with the dentist delivering the message of drug effects. When the dentist returned to give her the postplacebo forms, he found her 'almost asleep and very relaxed' (her words)
Psychopharmacology 57 (1978) References
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Received September 26, 1977
