This week I have had the honour of interviewing Dr Irving Kirsch. Dr Kirsch is Associate Director of the Program in Placebo Studies and lecturer in medicine at the Harvard Medical School and Beth Israel Deaconess Medical Center. He is also Professor Emeritus of Psychology at the University of Plymouth and the University of Hull in the UK and University of Connecticut in the US. He has published 10 books and more than 250 scientific journal articles and book chapters on placebo effects, antidepressant medication, hypnosis, and suggestion. He originated the concept of response expectancy. His meta-analyses on the efficacy of antidepressants were covered extensively in the international media and influenced official guidelines for the treatment of depression in the United Kingdom. His 2009 book, The Emperor’s New Drugs: Exploding the Antidepressant Myth, was shortlisted for the prestigious Mind Book of the Year award and was the topic of 60 Minutes segment on CBS and a 5-page cover story in Newsweek. In this interview, we discuss Dr Kirsch’s research into the placebo effect and the efficacy of drugs used for depression. In this episode we discuss: How, as an undergraduate student, Dr Kirsch became interested in behavioural therapy but that he doubted the rationale behind these approaches That this led to an interest in beliefs that people had and research into the placebo effect How, while working at the University of Connecticut, his research into the placebo led to an interest in the efficacy of antidepressant drugs when compared to placebo How his work led to the surprising conclusion that, were antidepressant drugs were concerned, the placebo effect was so large that there was very little room for a meaningful drug effect How this changed Dr Kirsch’s views on antidepressant drugs entirely, causing him to ask whether the risks were worth the small benefit for depressed patients That a belief that a person has can affect their response to a drug either in a positive way (placebo) or in a negative way (nocebo) Dr Kirsch found that there are many conditions that can show a profound placebo effect including depression, anxiety, irritable bowel syndrome, pain, Parkinson’s disease and asthma  That the placebo tends to have a greater effect in conditions that have a large psychological component when compared to functional disorders such as diabetes That placebo can have an effect even if the patient knows that they are taking an inactive tablet and that part of this response is down to classical conditioning That Dr Kirsch is working on ‘open-label placebo’ which is being able to prescribe placebo to patients without deception That Dr Kirsch used to refer depressed patients for antidepressant treatments, but that his research made him a disbeliever when looking at the evidence of efficacy when compared to placebo How, when you give someone a new treatment, that often will counter feelings of hopelessness that characterise depressive experiences That in looking at this size of this effect, it made clear that the difference between placebo response and antidepressant response was so small that it was not clinically significant That even drugs with very different modes of action resulted in virtually identical responses in patients, for example, Tianeptine, which is an SSRE (selective serotonin reuptake enhancer) and decreases serotonin levels between neurons, this drug should make depressed people worse but instead, it showed the same efficacy as SSRI antidepressants How, when looking at the clinical trials used to demonstrate antidepressant efficacy, it became clear that the obvious nature of antidepressant adverse effects meant that trial participants would often “break blind” and they would know if they were in the active drug group or the placebo group, this would naturally influence the results of the trial That, in a small number of studies, an active placebo was used, which was a substance that mimicked the side effects of the