A Brief History of Placebos and Clinical Trials in Psychiatry

Article excerpt

The history of placebos in psychiatry can be understood only in the context of randomized controlled trials (RCTs). Placebo treatments are as old as medicine itself, and are particularly effective in dealing with psychosomatic symptoms. In psychiatry, placebos have mainly been featured in clinical drug trials. The earliest controlled trial in psychiatry (not involving drugs) occurred in 1922, followed by the first crossover studies during the 1930s. Meanwhile the concept of randomization was developed during the interwar years by British statistician Ronald A Fisher, and introduced in 3 trials of tuberculosis drugs between 1947 and 1951. These classic studies established the RCT as the gold standard in pharmaceutical trials, and its status was cemented during the mid-1950s. Nevertheless, while the placebo became established as a standard measure of drug action, placebo treatments became stigmatized as unethical. This is unfortunate, as they constitute one of the most powerful therapies in psychiatry. In recent years, moreover, the dogma of the placebo-controlled trial as the only acceptable data for drug licensing is also being increasingly discredited. This backlash has had 2 sources: one is the recognition that the US Food and Drug Administration has been too lax in permitting trials controlled with placebos alone, rather than also using an active agent as a test of comparative efficacy. In addition, there is evidence that in the hands of the pharmaceutical industry, the scientific integrity of RCTs themselves has been degraded into a marketing device. The once-powerful placebo is thus threatened with extinction.

Can J Psychiatry. 2011 ;56(4): 193-197.

Highlights

* Placebos have always been used in medicine for their effectiveness in treating psychosomatic symptoms, yet, following the Second World War, this valuable psychiatric treatment was banished from clinical use as an instrument of deception.

* The main use of the placebo in modern psychiatry has thus been in the clinical drug trials, particularly with the development of the placebo-controlled RCT. The most intriguing development in the use of placebos for this purpose has been the extent to which the RCT, originally enshrined as the gold standard of clinical pharmacology, has been increasingly discredited in recent decades. This backlash has had 2 sources: growing awareness of the lax standards of the US Food and Drug Administration in mandating trials controlled by placebo alone, rather than also using the standard agent as a test of comparative efficacy; and growing evidence that the scientific integrity of RCTs themselves has been corrupted in the hands of the pharmaceutical industry.

Key Words: controlled trial, placebo treatment, randomized controlled trial

Abbreviations

FDA Food and Drug Administration

RCT randomized controlled trial

It is possible to understand the history of placebo treatments in psychiatry only in the context of controlled trials. Placebos have always been used clinically, though in the Freudian era agents of any kind were frowned on, whether placebo or active. The most intriguing aspect of placebos in clinical trials in psychiatry, however, is the extent to which RCTs themselves have shifted from a positive to a negative valence.

Placebo treatment has been known in medicine - and in psychiatry - since time out of mind, given that placebos are most effective in treating symptoms of psychological origin, or somatoform illnesses. As John T G Nichols1 of Harvard University wrote in 1893,

The average patient listens with much more interest to the prescription of his physician than to his directions about hygiene. Expecting good results from the drug, he often imagines that he feels them. So great is the power of hope that, even in incurable diseases, a temporary improvement often follows each new prescription. This power of hope ... is sometimes used by the educated physician, who calls it 'expectant attention. …