Most physicians make at least some use of the placebo effect to enhance treatments, whether they realize it or not. This article examines the extent of the placebo effect in patients with psychiatric illness, and reviews what is known about how placebos work. It then discusses the application of the placebo response in enhancing the effects of treatment modalities in psychiatry.
It is instructive to note a feature of virtually every antidepressant efficacy trial: in outpatients with moderately severe depression whose symptoms are assessed using the Hamilton Rating Scale, most of the improvement occurs during the first 2 weeks of treatment, and during this time, no differences in outcome between active drug and placebo are evident. After about 2 weeks, the placebo response reaches a plateau. Response to medication may continue to increase for a time, but during the period when most of the improvement occurs, placebo and medication produce similar responses.
In fact, the strength of the placebo response can be quite significant in several psychiatric disorders. 1 Panic disorder is highly responsive to placebo, with a nearly 50% improvement in symptoms among patients assigned to that treatment strategy. In patients with posttraumatic stress disorder or depression, the placebo response is greater than 30%, and a response in the 30% range is also seen in generalized anxiety disorder.
Patients with other conditions, including obsessive-compulsive disorder (OCD) and psychosis, are less likely to exhibit a placebo response. Clearly, the placebo response is not uniformly strong in all psychiatric conditions. We have used these findings as a basis for recommending that clinical trials of agents being tested in patients with psychiatric disorders always include a placebo arm. 1
Placebo vs pharmacotherapy or psychotherapy
How do responses to placebo compare with those achieved with medication? When treated with clonazepam or an SSRI, 60% to 70% of patients with panic disorder become panic-free during a 10-week treatment period. During the same period, half or more of patients with panic disorder who are treated with placebo become panic-free, underscoring the magnitude and importance of the placebo effect in this common condition. 2 Active drug treatment for depression leads to improvement in about 60% to 70% of patients, while placebo administration is followed by improvement in 30% to 40%, again an impressive contribution. 3
Conditions that are poorly responsive to psychotherapy are also unlikely to respond to placebo. Patients with attention-deficit/hyperactivity disorder, for example, are more likely to improve with medication than with behavior therapy. We would not expect a robust response to placebo in this patient group.
The results of a collaborative National Institute of Mental Health study on the treatment of depression are informative. 4 Most of the patients had unipolar disease and were mildly, moderately, or severely ill. Some were randomized to clinical management and placebo; they attended a clinic, were given a placebo pill, and asked how they were doing. Patients in other groups were randomly assigned to cognitive-behavioral therapy, interpersonal psychotherapy, or imipramine. When the results were analyzed, no differences in outcome were evident according to the various treatments. None showed any advantage over the others.
The analysis was also conducted according to whether patients were mildly or moderately/severely ill, and there the effects of some of the treatments did separate. In the less severely ill patients, no statistically significant difference was present among the treatments. In the more severely ill patients, imipramine, which was a popular antidepressant at the time the study was conducted, had an advantage over the 2 psychotherapies and placebo. Although there was a difference between the psychotherapies and placebo, it was not statistically significant. In the severely ill patients, imipramine worked better than any other treatment modality, but placebo was about as good as the psychotherapeutic strategies. 4
Although cognitive therapy for depression is widely used and taught in residency programs, the overwhelming majority of studies that have compared cognitive therapy with a pill placebo in the treatment of moderately severe depression show no difference in efficacy. 5,6 Less severely ill patients may benefit from any one of several different types of treatment, including psychotherapy, alternative therapies, and placebo.
The benefits of placebo treatment are, of course, not limited to psychiatry. In a review of hypertension therapy, it was documented that active pharmacologic agents were associated with a 40% to 60% rate of reducing blood pressure to the normal range, while placebo was associated with a 25% success rate. 7 Some neurologic conditions, asthma, and certain pain problems are also responsive to a placebo effect.
What is a placebo response?
In my opinion, the term placebo is misleading. In fact, patients who receive "placebo" treatment get much more than a sugar pill, whether they are enrolled in a placebo-controlled clinical trial or are the recipients of ordinary medical care. "Treatment situation" is a more evocative term than "placebo treatment," and it includes several essential elements associated with healing, as shown in Table 1 .
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