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When psychiatrist Peter Kramer, M.D., published his best-seller Listening to Prozac in 1993, he put forth the then-heretical thesis that the new serotonergic antidepressants, of which Prozac (fluoxetine) was the prototype, could alter personality in normal people as well as those with a defined psychiatric disorder.
He coined the term "cosmetic psychopharmacology" to describe how the new selective serotonin reuptake inhibitors (SSRI's) might be used by multitudes seeking to smooth out the rough edges of normal personality. After all, who wouldn't like to be a bit more poised, a tad more cheerful, a bit more attentive?
Regardless of whether skyrocketing sales of Prozac, Paxil (paroxetine), and other SSRI's are proof that cosmetic psychopharmacology has entered the mainstream or merely evidence that physicians are doing a better job of identifying and treating depression may depend on whom you ask. But according to two studies in consecutive issues of the American Journal of Psychiatry (AJP), the jury is still out.
In the February AJP, Yevgenia Gelfin, M.D., and colleagues from Hadassah Hebrew University Medical Center in Jerusalem described the effect of clinical doses of Prozac on healthy volunteers ("Effect of Clinical Doses of Fluoxetine on Psychological Variables in Healthy Volunteers"). In a single-blind, placebo study, 15 healthy subjects received placebo for two weeks, then 10 mg of Prozac daily for one week, then 20 mg of Prozac daily for five weeks, and then an additional two weeks of placebo.
There were few adverse effects, and "no significant effects attributable to fluoxetine were observed on any of the psychological variables examined," the study concludes.
The bottom line: "Significant mood elevating and other psychological effects of fluoxetine would appear to be induced only when symptomatic targets exist." In their discussion, the authors concede that their findings "contrast with the observations of [Peter] Kramer (whose subjects all had sought treatment) and suggest that mood-enhancing and other psychoactive effects of SSRI's are not a general property of these agents but are manifest in the context of target symptoms.
Given the controversy that followed the publication of Listening to Prozac and the book's hold on the popular imagination, it would have been rash to consider the Gelfin study the last word on this subject. And indeed, the March issue of AJP contains an article by Brian Knutson, Ph.D., and colleagues from the Langley Porter Psychiatric Institute at the University of California, San Francisco, in which they draw a radically different conclusion based on their four-week study of two dozen normal volunteers ("Selective Alteration of Personality and Social Behavior by Serotonergic Intervention").
After four weeks of observing normal subjects getting 20 mg daily of Paxil (paroxetine) versus a similar placebo control group, the authors report some intriguing results.
"Relative to placebo, SSRI administration reduced focal indices of hostility through a more general decrease in negative affect, yet did not alter indices of positive affect. In addition, SSRI administration increased a behavioral index of social affiliation." In other words, without a loss of positive feelings, those getting Paxil were more positive and more cooperative, as a result of diminished hostility.
While subjects in both this study and the Gelfin study filled out a variety of standard psychometric questionnaires, the Knutson study also had each subject solve various spatial puzzles in collaboration with another subject. The pairs always consisted of one SSRI- and one placebo-treated subject, and novel partners were assigned for each task. These puzzle-solving sessions were videotaped without the participants' knowledge, and coders blind to the subjects' status rated the video sessions for social behaviors suggesting cooperation. The SSRI-treated group "showed more affiliative behavior in the puzzle task than the placebo-treated group."
The authors conclude that "central serotonergic function may modulate a dimension of normal personality characterized by reduced negative affective experience and increased affiliative behavior. SSRI administration has significant and detectable effects on these measures even in the absence of baseline clinical depression or other psychopathology."
Their results complement the findings of studies with SSRI-treated male vervet monkeys, the authors note. The SSRI-treated monkeys also became more sociable, which, in turn, led to increased status. Sensitive to the implications for human society, the authors comment. "Affiliative behavior may raise one's status only in certain social contexts (e.g., in the absence of a preexisting dominance hierarchy, in the presence of peers who reciprocate affiliative behavior). Thus, while this work suggests that chronic SSRI administration can enhance affiliative behavior of normal volunteers in a cooperative task with novel partners, more research is needed on interpersonal effects of SSRI treatment in other types of social scenarios (e.g., competitive)."
Child psychiatrist Stanley Greenspan, M.D., author of The Growth of the Mind, thinks the differences in the AJP studies could be attributable to different methodologies. "You're dealing with very subtle shifts in behavior," said Greenspan. But he is more concerned about what the trend toward cosmetic psychopharmacology implies about society.
"Rather than explore and try to understand themselves, people can resort to medication as a way of changing their biology. I am very concerned; I think it's a worrisome trend. I think we have to turn back to a basic developmentally based biopsychosocial model where we give equal weight to psychodynamic and family relationships."
Psychiatry, said Greenspan, "plays a major role in how we think about ourselves. Human beings are not just "a bundle of neurochemicals.
While both studies were too short to definitively answered the question that has been raised, it is true that any drug that alters abnormal personality is likely to alter normal personality as well, said Frederick Goodwin, M.D., director of the Center on Neuroscience, Medical Progress, and Society at George Washington University in Washington, D.C. Goodwin, however, is far more concerned about underdiagnosis of depression and underuse of SSRI's than about the trend toward cosmetic psychopharmacology.
"There are data from NIMH surveys showing that undertreatment [of depression] is still more of a problem" than inappropriate use of SSRI's, for which there are not good data, he observed.
-R.B.K.