Placebos and Antidepressants

Want to know where we get the ‘up to 70% success’ claim in our packaging?

"The placebo response, noted as an early or nonpersistent improvement in response to an inactive agent, represents one of the most significant challenges in central nervous system (CNS) drug development. Despite a wealth of documentation, there is no commonly accepted definition of this phenomenon. However, it is agreed that there has been a significant increase in the placebo response in the last 20 years, particularly in clinical trials with antidepressant medications for major depressive disorder (MDD).

Estimates as high as 70% have been reported for CNS clinical trials. (our italics) Such large placebo rates have a significant impact on the cost and speed of drug development.

Since fewer than half of the depressed patients who receive active medications in psychiatric trials show clinically significant improvement, some critics claim that antidepressants are no better than placebo treatment, and their illusory superiority depends on poorly designed studies and biased clinical evaluations. In a set of six identically designed, three-arm, parallel controlled trials submitted to the Food and Drug Administration for an antidepressant drug, Leber reported that antidepressants could not be distinguished from placebo in five of the six studies."

Ref. Richard Entsuah, Phil Vinall: Potential Predictors of Placebo Response: Lessons From a Large Database, Drug Information Journal. Ambler: 2007. Vol. 41, Iss. 3; pg. 315, 16 pgs

Is your Doctor Prescribing a Placebo?

An article in the Journal of General Internal Medicine explores the actual use of placebos by conventional doctors


Background – The placebo and the placebo effect are often investigated in the context of clinical trials. Little data exist on the use of placebos in the course of routine health care.

Objective – The aim of this study is to describe a group of academic physicians’ use of placebos and their knowledge, attitudes, and beliefs about placebos and the placebo effect.

Design – A 16-question anonymous web-based survey of physicians from Internal Medicine departments of 3 Chicago-area medical schools was used.

Results – There were 231/466 (50%) physicians who responded; of these, 45% reported they had used a placebo in clinical practice. The most common reasons for placebo use were to calm the patient and as supplemental treatment. Physicians did not widely agree on the definition of a placebo and had a variety of explanations for its mechanism of action. Ninety-six percent of the respondents believed that placebos can have therapeutic effects, and up to 40% of the physicians reported that placebos could benefit patients physiologically for certain health problems. Only 12% of the respondents said that placebo use in routine medical care should be categorically prohibited. Regarding “placebo-like” treatment, 48% of respondents reported giving at least 1 type of treatment in a situation where there was no evidence of clinical efficacy.

Conclusion – Nearly half of the respondents use placebos in clinical practice and most believe in the mind–body connection. The results of this study, based on retrospective self-reported behavior, are subject to recall bias and may not be representative of American physicians.

"Academic Physicians Use Placebos in Clinical Practice and Believe in the Mind–Body Connection"
– Rachel Sherman and John Hickner (University of Chicago Pritzker
School of Medicine), Journal of General Internal Medicine, Volume 23,
Number 1 / January, 2008

Placebo Surgery

Amazing placebo experiment with knee surgery – points to the finding that there can be ‘grades’ in the placebo effect – big pills are more effective than small pills, coloured pills more effective than white ones, inert injections more effective than pills, and sham surgery more effective than any of them.
Of course, at Universal Placebos we feel it sufficient to stay with our modest, aesthetically pleasing, small white sugar pills, in doses of three. That’s enough.

What Happens When You KNOW You’re Taking a Placebo?

One of the rare studies into the action of the placebo effect in ‘non-blind’ clinical trials was undertaken by Lee C. Park and Uno Covi at the Johns Hopkins University School of Medicine in 1964. ‘Non-blind’ means that patients were informed that the pills they were issued were totally inert, that they were placebos, and in this case they were also assured that despite this the pills would be of benefit to them. The study concluded:’The primary finding is that patients can be willing to take placebo and can improve despite disclosure of the inert content of the pills; belief in pill as drug was not a requirement for improvement.’

(Some first-hand reports on our Testimonials page.)

Ref. L. C. Park, U. Covi, Nonblind Placebo Trial – An Exploration of Neurotic Patients’ Responses to Placebo When Its Inert Content Is Disclosed, Archives of General Psychiatry, April 1965, Vol. 12, pp. 336-345

Placebos and Sinusitis

Placebo As Good As Common Treatments For Sinus Infections

A placebo is likely to be just as effective as common acute sinusitis treatments involving a topical steroid and an antibiotic, according to an article published in the Journal of the American Medical Association.

Ian G. Williamson, MD; Kate Rumsby, BA; Sarah Benge, PhD; Michael Moore, FRCGP; Peter W. Smith, PhD; Martine Cross, BA; Paul Little, MD – “Antibiotics and Topical Nasal Steroid for Treatment of Acute Maxillary Sinusitis – A Randomized Controlled Trial”, Journal of the American Medical Association. 2007;298(21):2487-2496.

‘True’ and ‘Perceived’ Placebo Effects

One of the problems scientists have in evaluating the placebo effect is the distinction that can be drawn between ‘true’ and ‘perceived’ placebo effects, where a ‘perceived’ effect might not not be directly attributable to the administration of a placebo. But they also acknowledge the general ignorance of definition and description when it comes to the ‘true’ placebo effect.’A review of the literature shows that most authors confuse the perceived placebo effect with the true placebo effect. The true placebo effect is highly variable, depending on several factors that are not fully understood.’

Ref. E. Ernst, K. L. Resch, Concept of true and perceived placebo effects, British Medical Journal, 1995;311:551-553

Using Placebos in Clinical Practice?

A few – just a few – medical professionals bring up the ethics of therapists actually prescribing placebos as an element of treatment.

Margaret Talbot proposes in the New York Times Magazine (1/09/2000):"The truth is that the placebo effect is huge — anywhere between 35 and 75 percent of patients benefit from taking a dummy pill in studies of new drugs — so huge, in fact, that it should probably be put to conscious use in clinical practice, even if we do not entirely understand how it works."

Others might balk at the suggestion, but there seems to be an ethical shadow-line, where a drug-focused therapy may overlap with the physician’s responsibility (duty?) to care for his or her patient as more than a machine, as a being of heart-mind."The placebo effect can occur," as the physician Herbert Spiegel once put it, "when conditions are optimal for hope, faith, trust and love." It might sound sentimental, but then sentiment, working hand in hand with science, can make medical practice so much more powerful. A world in which placebo — preferably in the form of deft encouragement, but sometimes in the form of a harmless pill — was tolerated, even embraced, would be a world in which doctors never forgot that medical practice consists not only of the technologies of diagnosis and treatment but also of the careful tending of a patient’s expectations and the unabashed willingness to comfort."

Margaret Talbot, The Placebo Prescription, New York Times Magazine

Skeptics Have Two Bob Each Way

Even the skeptics (American English for ‘sceptics’) can’t come down *too* hard on placebos:

"A person’s beliefs and hopes about a treatment, combined with their suggestibility, may have a significant biochemical effect. Sensory experience and thoughts can affect neurochemistry. The body’s neurochemical system affects and is affected by other biochemical systems, including the hormonal and immune systems. Thus, it is consistent with current knowledge that a person’s hopeful attitude and beliefs may be very important to their physical well-being and recovery from injury or illness.
However, it may be that much of the placebo effect is not a matter of mind over molecules, but of mind over behavior. A part of the behavior of a "sick" person is learned. So is part of the behavior of a person in pain. In short, there is a certain amount of role-playing by ill or hurt people. Role-playing is not the same as faking or malingering. The behavior of sick or injured persons is socially and culturally based to some extent. The placebo effect may be a measurement of changed behavior affected by a belief in the treatment. The changed behavior includes a change in attitude, in what one says about how one feels, and how one acts. It may also affect one’s body chemistry.

From The Skeptics Dictionary

The Placebo Effect and Depression

Placebo Effect Accounts for Fifty Percent of Improvement in Depressed Patients Taking Antidepressants (1996 Press Release, American Psychological Association)

TORONTO — The debate about treating depression with drugs, psychotherapy, or a combination of both drugs and psychotherapy has raged on over the years. But a recent analysis of 39 studies of 3,252 depressed patients, presented at the American Psychological Association’s (APA) 104th annual convention, found that 50 percent of the drug effect is due to the placebo response.


In other words, a patient taking antidepressant medication with a self-reported improvement rate of 10 points, can attribute half (.5) of that improvement to the placebo effect. To determine the placebo effect of antidepressant medications, psychologist Guy Sapirstein, Ph.D., at the University of Connecticut, analyzed 39 studies of depressed patients from 1974 to 1995. The studies included patients with a primary diagnosis of depression, were randomized, and controlled for patients who received no treatment.

Studies that measured the effects of antidepressant medications such as fluoxetine (Prozac), sertaline (Zoloft) and paroxetine (Paxil) were included in the analysis. Dr. Sapirstein concluded that the pharmacologic and nonpharmacologic effects of antidepressants indicates that while only 27 percent of the response to medication is due to the medication alone (a true pharmacologic effect), 50 percent is due to the psychological impact of administering the medication (placebo effect) and 23 percent is due to other ‘nonspecific factors.’ ‘People benefitting from drugs are benefitting because they think that taking the antidepressant medicine is working,’

Dr. Sapirstein said. ‘If we take these results and say that improvement is due to what the patients think, then how people think and its effect on how they feel are more powerful than the chemical substance,’ he added. In addition, the study found that patients who either took medication or underwent psychotherapy exclusively had similar treatment outcomes. The promise of future treatment, which was controlled for by the wait-listed patients, did not affect depression levels.