ABOUT DRUGS

           
 PSYCHOPHARMACOLOGY
Although psychopharmacology is a relatively new scientific word, the interactive effects of drugs and behavior are perhaps as old as man himself. This presentation will describe contemporary interest in psychopharmacology and will emphasize the social research frontiers. It will not attempt to describe the emerging body of human and animal research results or the treatment aspects of drugs.


Although there are clearly a number of focuses for discussion, the individual human has been selected as the center of analysis; this article will deal with a number of individual and social factors relating to the effects of drugs. These factors are complex and generally poorly identified and weakly conceptualized. The ramifications of the questions lead one to consideration of the pathways of activity in the nervous system, the complexities of biochemical analysis, the assessment of human performance in laboratory or simulated situations, the management of patients, and the social matrix in which all of human behavior is embedded.


Historical considerations. Drug utilization for health, religious, or individual purposes is one of the many primary characteristics of human behavior in a wide variety of cultures. Drugs thus constitute an almost universally present element in human social behavior, and one to which individual reinforcement, social training, and private meaning are attached. One of the world’s oldest professionals, the medicine man, has long made use of a variety of chemical substances in the technology of his affairs.


Although the term “psychopharmacology” has been used with increasing frequency over the past few years, the concept is by no means new to psychology. Studies of the effects of drugs on the behavior of animals were undertaken in the nineteenth century, and the classic investigations of the effects of caffeine on human behavior were carried out by Hollingworth (1912) in the first decade of the twentieth century. This series of studies embodied many of the aspects of good design and may still have value as a model for analysis of the effects of drugs on human behavior.


The current dramatic expansion of interest in psychopharmacology as a special area dates from the early 1950s. In its early phases it was a product of the joint action of pharmacologist and psychiatrist in their attempts at modification of the behavior of psychiatric patients.


Since the early 1950s, when drugs such as reserpine and chlorpromazine were introduced, the list of compounds has grown, although some central questions surround these drugs and their utilization.


Problems. Any real understanding of drugs that affect behavior depends upon the development of adequate theory relating biochemical or pharmacological events to behavioral events. Callaway and Stone (1960) have examined the nature of theory in this area and find that an integrating theory is still to be developed. On the biochemical side they find that the problem is formidable and aggravated by the lack of appropriate behavioral referents. Theories proposed by behavioral scientists may greatly oversimplify the underlying biological complexities. On the other hand, theories constructed by biochemists and pharmacologists may be naive about the behavioral complexities. No available theory is consistent with the available data, and many approaches use ambiguous and subjective terms. Callaway and Stone express the hope that the new psychotropic drugs can serve as a valuable class of independent variables in an integrated theory of behavior.


The task of analyzing the specific pharmacological effects of a drug is confounded by the history, learned expectations, and social roles of the individuals involved. Poffenberger (1942, pp. 200–202) discussed several major sources of error in drug investigations. He expressed serious concern about the “suggestibility of people who have a knowledge of the effects to be expected,” the lack of control subjects, the difficulties in the selection of appropriate measures of drug effects, the short duration of drug studies, and, finally, the facts of interindividual and intraindividual differences [seeSuggestion].


Modell has recently reviewed the problem of experimental controls in clinical pharmacology. He writes:


It may surprise some laboratory workers as well as a large number of clinicians that the pharmacologic experiment in man is really far more difficult than in the animal. The training and the orientation of the physician, as well as his relationship to the patient, make him an interested and purposive observer rather than a precise and objective one. Also realistic restrictions on the techniques that may be used in making observations on man make the clinical experiment difficult to perform and limit the depths which can be proved directly. Then there is the subject, whose human mind, human culture, human society, and human frailties make it uniquely difficult to experiment on him. All of these factors make the establishment of controls in a human experiment quite a different kettle of fish from the laboratory procedure of dividing littermates into two equal groups. (1963, p. 372)


Methodological developments
Experimenter and subject bias are presumably dealt with by the double-blind control, in which both E and S are prevented from knowing who has been assigned to a specific experimental group. The placebo presumably is utilized to deal with the implications of medication, and randomization of other variables permits dealing with extraneous factors. The advantages and liabilities of the double-blind procedure have been discussed by Nash (1962) and need not be pursued here [seeExperimental design].


Placebo effects and research design
The placebo issue has also been of much interest and has been reviewed by Wolf (1959) and by Roueche (1960, pp. 85–98). Beecher (1955) has stressed the importance of the placebo concept, distinguishing between the effects of suggestion and the direct pharmacological effect. Wolf defines placebo effect as “any effect attributable to a pill, potion, or procedure, but not to its pharmacodynamic or specific properties” (1959, p. 689).


An experimental design involving an extra group of subjects in addition to the usual drug, placebo, and untreated groups has been developed (Ross


Table 1
  DRUG NO DRUG
PILL Drug Placebo
NO PILL Drug disguised Nothing
et al. 1962; Lyerly et al. 1964). This extra group, called the “drug disguised group,” receives the drug in a disguised form. Table 1 outlines this fourfold design.


The main question to which this design is directed is the analysis of drug effects. Most studies are based on a drug group—placebo group design or, less frequently, a drug group-placebo group-untreated control group design. In the typical drug—placebo experiment, both drug and placebo groups are given pills with the same instructions. The effects observed in the drug Ss are generally attributed to the pharmacological properties of the agent after subtraction of the effects found in the placebo Ss. But these “drug” effects may be partly a function of Ss’ expectations or of the experimental or therapeutic setting. When a nontreatment group is added to the design, however, the differences between the untreated and the placebo groups can be attributed to the placebo effect. The special advantage of the four-group design is that it permits direct assessment of drug and placebo effects. In a typical experiment the drugs and placebos were given to the Ss in capsules, and all Ss received orange juice, which was also the vehicle for the disguised medication. The untreated group received orange juice only.


One experiment has been reported on the effects of d-amphetamine sulfate. The results of this experiment, carried out with neutral instructions, indicated a positive pill effect on mood, that is, the S felt more “comfortable,” and a negative effect of the drug when administered in the disguised condition. The untreated group provided results similar to those of the group that received the drug as a pill. Motor performances of both the drug and the drug-disguised groups were significantly poorer than those of the placebo and untreated groups.


Effects of expectancies. A second experiment was designed to determine the specific effects of direct and conflicting instructions and the effects of two drugs (amphetamine sulfate and chloral hydrate) that might be expected to produce different pharmacological and perceptual effects. Two sets of instructions were developed to lead Ss to expect that the capsules they swallowed would yield the specific effects of one of the two drugs. Groups similar to those in the previous experiment were used.


Instructions alone affected motor performance but had little or no effect on mood. Direct instructions, appropriate to the presumed drug effects, produced performance deterioration with the simple motor tasks used. Conflicting instructions, inappropriate to the presumed drug effects, counteracted much of the drug-produced decrement. A slight decrement in performance was found in the placebo group which received instructions appropriate to the effects of amphetamine. Amphetamine produced reports of greater comfort on the “mood index” than did chloral hydrate. On the other hand, the chloral hydrate instructions resulted in greater comfort than the amphetamine instructions. There was no interaction between drug effects and instructional effects. The two placebo groups did not differ significantly on the mood index. The effects of instructions on mood were found only when the drug was present.


The general problem of placebos has been analyzed from a variety of viewpoints (Fisher 1962; Gorham & Sherman 1961; Hawkins et al. 1961; Kast 1961; Wilson & Huby 1961) and is far from settled.


Personality and social aspects
Increased sophistication has been emerging in the field of human experimentation, stimulated by analyses of the social psychology of the psychological experiment (Orne 1962; Rosenthal 1963). The issue of ecological validity and the appropriate generalization from the laboratory to nonexperi-mental situations were treated by Brunswik (1947). Perhaps it is fair to say that the problem has not received its appropriate emphasis to date. Orne has suggested that the subject must be recognized as an active participant in any experiment and that it may be fruitful to view the psychological experiment as a special form of social interaction. He has proposed that the behavior of the subject is a function of the total situation, which includes the experimental variables being studied and at least another set of variables. The latter group has to be put under the heading of “demand characteristics” of the experimental situation. Rosenthal has described a program of research dealing with experimenter bias. It is shown that the expectation of the experimenter was a partial determinant of the results of behavioral research. The issues in these studies are vital ones for psychopharmacology, and it is hoped that future research will attend to these problems.


Drug therapy
A recent analysis of psycho-pharmacology and personality takes stock of personality measurement in relation to drugs. It reports the rather meager progress in psychopathology and deduces a static plateau in personality measurement “cushioned by factor analysis on the one hand and by psychodynamics on the other” (Zubin & Katz 1964).


In the specific domain of the treatment of hospitalized psychiatric patients, additional aspects of the effects of drugs become of interest to the social scientist. Klerman (1961) states that before the 1930s major interest lay in such disorders as general paresis or epilepsy. Metrazol, electroconvulsive therapy, insulin coma, and lobotomy made their appearance at this time. It was in the decade before World War ii that schizophrenia became the center of attention. Psychotherapeutic innovation also appeared under the leadership of Harry Stack Sullivan, Jacob Moreno, Frieda Fromm-Reichmann, and others. Klerman indicates that it is unfortunate for drug evaluation that the advent of the newer tranquilizing agents in the 1950s coincided with a wave of hospital reforms and innovations in the treatment of psychotic patients. This interaction is a complex one, and it is difficult to assess the effects of “drugs” on hospital admission, readmission, and other rates.


In addition to affecting the individual patient or subject the psychotropic drugs also affect the hospital milieu and functional organization. Elkes has described this interaction as follows:


In an age of revolutions, one is apt to get used to revolutions. In considering the impact of the pharmacotherapies on the management of the psychoses in a mental hospital, one is apt to be reminded of the violent changes brought about in the past by the introduction of other somatic therapies, such as deep insulin coma, electroplexy, and the lobotomies. Each of these has wielded changes, based essentially upon relatively short-term results; only in recent years could these be viewed against the perspectives of long-term follow-up studies. The changes in management, and the attendant changes in attitude, however, have stayed and become cumulative. It is quite possible that a similar fate may befall the pharmacotherapies of mental disorder, though three important differences distinguish them from earlier treatments and encourage a more hopeful view. The first is the fact that these therapies can be graded and made individual in a way which was quite impossible with the less variable and massive procedures used in the past. Secondly, they can be used on a scale far larger than the earlier therapies. Thirdly, whereas in the past systematic studies of mode of action followed essential empirical findings and measures, the empirical findings of the pharmacotherapies are being increasingly related to a growing body of modern theoretical neuropharmacology and neurochemistry. Theories are thus likely to keep abreast of clinical findings in a way never before witnessed in psychiatry, and are likely to make these ever more precise, discriminate and long-term.


The impact of the drug therapies on mental hospital population is essentially threefold. They have altered the immediate management and treatment of certain types of acutely disturbed psychotic patients; they have mobilized large chronic populations hitherto secluded in the continued-treatment units of the average mental hospital; and, in individual cases, have made possible measures of rehabilitation which would have been very difficult to achieve in their absence. Lastly, they have increased and made more urgent the contacts between the mental hospital and the community. In terms of all these effects the drugs are wielding profound changes in staff attitudes at all professional levels. The precise pattern of these changes at present is far from clear, and for the moment can only be discussed in the broadest terms. (1961, pp. 91–92)


With respect to the clinical treatment of the chronically hospitalized patient, there has long been evidence that increases in staff attention alone will produce symptomatic improvement (Galioni et al. 1953). A recent study by Bullard, Hoffman, and Havens (1960) indicates that drugs may be more important than environment in producing changes in chronic patients. An excellent review of this problem by Hordern and Hamilton (1963) indicates its complexities and the lack of clarity regarding the contributions to patient response of drugs and special nondrug treatments and of staff and patient attitudes. It is unfortunate but true that the effects of the drug and/or environment found in any single study represent only a single case in the larger sense, since it is almost impossible at present to measure or even meaningfully hypothesize what aspects of the staff–patient–milieu–drug context are responsible for the effects produced.


The introduction to a recent volume on specific and nonspecific factors in psychopharmacology states the central issue cogently: “The concept of specificity of drug action is at the heart of all pharmacological enquiry and speculation, and the stated hope of chemotherapy. Yet, in the unfamiliar terrain now extending between biochemistry and behavior, the term is assuming new and unexpected meaning. The interaction between the somatic and the symbolic compels a revision of premises, a recalibration of tools, and a reassessment of rules” (Elkes 1963, p. v). In this revision, recalibration, and reassessment, all of the sciences of man are involved. The social sciences have their special assignment and central contribution.