Abstract
This article concerns the challenges faced by pharmaceutical researchers seeking to develop novel antidepressants. Based on ethnographic and documentary research into the drug development process, it shows how researchers try to manage the problem of the placebo response in antidepressant trials. The high rate of placebo response in these trials makes it difficult to demonstrate efficacy and often leads to trial failure. According to researchers, a major reason for high placebo response rates is the inability of standardized rating scales to define a coherent group of ‘drug responders’. They have developed alternative means of classifying patients in order to circumvent this problem and thereby improve the chances of trial success. In their search for ‘the right patients for the drug’, pharmaceutical researchers also provide an incisive critique of the epistemological assumptions underlying the clinical trial process.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Notes
1 Indeed, the development of rating scales was a precursor to a major and controversial effort to standardize clinician diagnostic practices, the 1980 Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-III). See Lakoff (2005).
2 As Charles Rosenberg (1992: 309) argues, the understanding of an illness as a specific entity ‘is a fundamental aspect of the intellectual and moral legitimacy of disease’ in contemporary biomedicine.
3 In this sense, symptom rating scales are an example of a technology of distrust (Porter, 1995).
4 As Espeland and Stevens (1998: 321) write, commensuration ‘standardizes relations between disparate things and reduces the relevance of context’.
5 Leber (2000) notes that in a set of six identically designed, three-arm, parallel controlled trials submitted to an NDA for a new antidepressant, a marketed antidepressant being used as a standard control agent could not be distinguished from placebo in five of six studies.
6 As Clifford Geertz (1983) writes, ‘Men plug the dikes of their needed beliefs with whatever mud they can find.’ In this case it is not a question of a belief system, but of a form of rationality embedded in the clinical trial apparatus.
References
Bodewitz H., Buurma H., & de Vries G.H. (1987). Regulatory science and the social management of trust in medicine. In Bijker W. Hughes T. & Pinch T. (Eds), The social construction of technological systems: New directions in the sociology and history of technology. Cambridge, MA: MIT Press.
Ehrenberg A. (1998). La Fatigue d’être soi. Paris: Odile Jacob.
Espeland W.N., & Stevens M.L. (1998). Commensuration as a social process. Annual Reviews in Sociology, 24, 313–43.
Faries D.E., Heiligenstein J.H., Tollefson G.D., & Potter W.Z. (2000). The double blind variable placebo lead-in period: Results from two antidepressant clinical trials. Journal of Clinical Psychopharmacology, 21, 561–8.
Geertz C. (1983). Local knowledge: Further essays in interpretive anthropology. New York: Basic Books.
Goode E. (2002). Antidepressants lift clouds, but lose ‘miracle drug label’. New York Times, 30 June.
Hamilton M. (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry, 23, 56–62.
Hamilton M. (1972). Rating scales in depression. In Krelholze P. (Ed.), Depressive illness: Diagnosis, assessment, treatment. Baltimore, MD: Williams & Wilkins Co.
Harrington A. (2002). ‘Seeing’ the placebo effect: Historical legacies and present opportunities. In Guess H.A. Kleinman A. Kusek J.W. & Engel L.W. (Eds), The science of the placebo: Toward an interdisciplinary research agenda. London: BMJ Books.
Healy D. (1996a). The antidepressant era. Cambridge, MA: Harvard University Press.
Healy D. (1996b). The psychopharmacologists. New York: Altman.
Kaptchuk T.J. (1998). Intentional ignorance: A history of blind assessment and placebo controls in medicine. Bulletin of the History of Medicine, 72, 389–433.
Kleinman A. (1988). Rethinking psychiatry: From cultural category to personal experience. New York: Free Press.
Kramer M.S., Cutler N., Feighner J., Shrivastava R., Carman J., Sramek J.J. et al. (1998). Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science, 281, 1640–1645.
Krishnan K. (2000). Efficient trial designs to reduce placebo requirements. Biological Psychiatry, 47, 724–726.
Lakoff A. (2005). Pharmaceutical reason: Knowledge and value in global psychiatry. Cambridge: Cambridge University Press.
Langreth R. (2002). Betting on the brain. Forbes, 7 January, 56–59.
Lasagna L., Mosteller F., von Felsinger J.M., & Beecher H.K. (1954). A study of the placebo response. American Journal of Medicine, 16, 770–779.
Leber P. (2000). The use of placebo control groups in the assessment of psychiatric drugs: An historical context. Biological Psychiatry, 47, 699–706.
Lévi-Strauss C. (1963). The sorcerer and his magic. In Structural anthropology, trans. Jacobson C. New York: Basic Books.
McNair D.M., Gardos G., Haskell D.S., & Fisher S. (1979). Placebo response, placebo effect, and two attributes. Psychopharmacology, 63, 245–350.
Marks H. (1997). The progress of experiment. Cambridge: Cambridge University Press.
Moerman D. (1997). Physiology and symbols: The anthropological implications of the placebo effect. In Romanucci-Ross L. Moerman D.E. & Tancredi L.R. (Eds), The anthropology of medicine: From culture to method, 2nd edn. Westport, CT: Bergin & Garvey.
Montgomery S.A. (1999). The failure of placebo-controlled studies. European Neuropsychopharmacology, 9, 271–276.
Nuland S. (2001). The uncertain art: Mind, body, and the doctor. American Scholar, summer: 123–126.
Pignarre P. (2001). Comment la dépression est devenue une épidémie? Paris: La Découverte.
Porter T. (1995). Trust in numbers. Princeton, NJ: Princeton University Press.
Quitkin F. (1999). Placebos, drug effects, and study design: A clinician's guide. American Journal of Psychiatry, 156, 829–836.
Quitkin F.M., McGrath P.J., Stewart J.W., Ocepek-Welikson K., Taylor B.P., Nunes E. et al. (1998). Placebo run-in period in studies of depressive disorders: Clinical, heuristic and research implications. British Journal of Psychiatry, 173, 242–248.
Quitkin F.M., Rabkin J.G., Gerald J., David J.M., & Klein D.F. (2000). Validity of clinical trials of antidepressants. American Journal of Psychiatry, 157, 327–337.
Rosenberg C. (1992). Explaining epidemics, and other studies in the history of medicine. Cambridge: Cambridge University Press.
Schatzberg A.F., & Kraemer H.C. (2000). Review of placebo control groups in evaluating efficacy of treatment of unipolar major depression. Biological Psychiatry, 47, 736–744.
Timmermans S., & Berg M. (1997). Standardization in action: Achieving local universality through medical protocols. Social Studies of Science, 27, 273–305.
Trivedi M.H., & Rush H. (1994). Does a placebo run-in or a placebo treatment cell affect the efficacy of antidepressant medications? Neuropsychopharmacology, 11, 33–43.
Womack T., Potthoff J., & Udell C. (2001). Placebo response in clinical trials. Applied Clinical Trials, February, 32–44.
Acknowledgements
I am grateful to Mireille Abelin, Elizabeth Bromley, Joe Dumit, Steve Epstein, Arthur Kleinman, Natasha Schull and Stefan Timmermans for their helpful suggestions in the course of this research and writing.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lakoff, A. The Right Patients for the Drug: Managing the Placebo Effect in Antidepressant Trials. BioSocieties 2, 57–71 (2007). https://doi.org/10.1017/S1745855207005054
Published:
Issue Date:
DOI: https://doi.org/10.1017/S1745855207005054