Andrew Leuchter, M.D. is Professor and Vice Chair of the Department of Psychiatry and Biobehavioral Sciences at the David Geffen School of Medicine, UCLA. He is also Director of the Division of Adult Psychiatry and senior research scientist at UCLA Neuropsychiatric Institute and Hospital.

Leuchter received his undergraduate degree from Stanford University, and his medical degree from the Baylor College of Medicine. He completed his residency at the UCLA Neuropsychiatric Institute, and a Robert Wood Johnson Fellowship in the UCLA Department of Medicine. Leuchter's clinical expertise is in the treatment of depression, with a special focus on treatment-resistant and late-life depression. The thrust of his research is the enhancement of treatment outcomes in depression. He uses brain imaging techniques such as quantitative electroencephalography (QEEG), magnetic resonance imaging (MRI), and positron emission tomography (PET) to examine brain function and predict which treatments are most likely to benefit individual patients. His research program combines clinical trials with neurophysiologic and brain imaging studies to inform clinical practice in the treatment of depression.

Leuchter is Board Certified in Psychiatry, has Added Qualifications in Geriatric Psychiatry and is Board Certified in Electroencephalography. He is the author of numerous articles and chapters on the assessment and treatment of depression, dementia and other major mental illnesses, and is the author of two patents for new methods to analyze brain electrical activity.

David Ramirez asks:
What about comparing placebo to no treatment at all? Hrobjartsson et al in their 2001 New England Journal Article found little difference between placebos and no treatment in a variety of ailments (pain being a possible exception)...

Leuchter's response:
The conclusions of Hrobjartsson and colleagues are easily misunderstood. First, they conducted a pooled analysis of data across many different illnesses, using 40 different outcome measures. There are serious scientific limitations with this type of "metaanalysis" and many researchers have questioned the reliability of the findings. Second, all of these studies had a "no treatment" arm, such that the subjects knew that they might be placed into a waiting-list treatment condition. This group of subjects is not typical of most of the patients receiving treatment, and might be less likely to show a placebo response. Third, Hrobjartsson and co-authors did conclude that for illnesses where the primary outcome was subjective complaint (including pain and depression), there was a placebo effect. Some of what we call the placebo response may in part be the natural remission of illness, and it is desirable to have a no-treatment group for comparison purposes. It is difficult, however, to withhold treatment totally: many patients will not submit to such studies, and it is difficult to interpret findings even if they do.

Rachel Carpenter asks:
Hi Dr. Leuchter,

Although I found the show and the inadvertent results of your research fascinating and certainly worthwhile, I was also very disturbed by the fact that some of the subjects who had been on an antidepressant previous to signing up for the study expected to go on a new medication (for free, I assume), and were willing to try it, to be the guinea pigs. It did not seem that they knew that they might be given a placebo.

It struck me as amazing that the gentlemen featured on the show

1) was cheerfully being interviewed and
2) that there wasn't a sort of review process used that would flag such cases. Or was there?

It seems to me that any drug trial is playing with fire. What if this man had attempted suicide while on the placebo? (Did he sign have to sign a non-liability waiver or whatever before he was allowed into the study?)

Your brain research led to unexpected, and very worthy, information about how the brain reacts to placebo drugs. Now you're researching how the placebo effect works in therapy, with the "less warm" doctor and the "warm" doctor. I would think that in many ways some of my concerns stated above apply here, too. I hope that, having found a new area of research (one that explores, among other things, the doctor-patient connection and relationship), you and your colleagues will take into account the possible dangers involved, and take steps to protect your subjects. I would like to know what steps you are taking in this regard. (By the way, I'm with Alan Alda on preferring "less warm" doctor to "warmer" doctor!) Very best,
and best of luck,
Rachel Carpenter

Leuchter's response:
I would very much like to comment on the circumstances of treatment for the gentleman who was interviewed on the show. For reasons of confidentiality, however, I am unable to do so. I can tell you, however, that we take the ethical issues that you raise very seriously. All of our studies are reviewed and approved by an Institutional Review Board whose sole purpose is the protection of subject welfare. This subject (along all others) was fully informed that if they participated in the study, they stood a 50:50 chance of receiving placebo. All subjects were interviewed to ensure that they understood that they might be receiving placebo, and signed a consent form to this effect.

We do everything that we can to ensure patient safety, and minimize any risks associated with placebo-controlled treatment. We do not enroll subjects with the most serious cases of depression, and we exclude patients who are actively suicidal. We believe that with all these precautions, our research is safe and will lead to improved treatment for depression in the future.

Regarding the "warmer" and "less warm" doctors, I frankly did not like either of them. I am not nearly as good an actor as is Alan!

Ankit Sur asks:
Hi Dr. Leuchter,
When I saw that Alan preferred the detached, more businesslike physician instead of a warmer, more empathetic one, I started thinking why that might be. I believe that this is the case because the warmer, more empathetic doctor alarms the patient; since it makes that patient think that something is seriously wrong with him/her that is why the doctor is so concerned. On the other hand, the detached, more businesslike physician doesn't make the patient feel that something is seriously wrong with him/her, since he comes in asks the needed questions and leaves. The detached, businesslike physician might enhance the placebo effect since it might give the patient more confidence in the medication that he/she is taking.

On the other hand, the warmer, more empathetic doctor might deteriorate the placebo effect since he might make the patient hesitant towards the medication. Overall, I was really impressed with your work.
Thanks,
Ankit

Leuchter's response:
Thank you for your kind comments about our work. I have found that different patients prefer doctors with different styles of interaction. Some patients prefer a more personal approach, some a more detached approach. As you suggest, people may find one or the other approach more reassuring, and have many different reasons for preferring one style over another.

Beth Epstein asks:
Dear Dr. Leuchter,
I am curious to know if there was a personality assessment (MBTI or other) component to your study.

If the assumption of Jungian archetypes is accepted, then the lifelong reinforcement of such preferences would likely demonstrate themselves in the "effectiveness" of the placebo effect, particularly in regards to the significance of the attitude of the patient-facing doctor. This seems likely in at least two ways.

First, certain temperaments in MBTI are more naturally prone to believing in authority figures than others. Generally speaking, the SJ temperament is more likely to accept the notion that "doctor knows best". The placebo effect might therefore be easier to evoke in SJ volunteers because of the doctor's role itself. Other temperaments, such as the more naturally skeptical NT might need more clinical, data-like input to experience the same effect.

Second, certain types in MBTI are more likely to appreciate the doctor's sympathetic approach to the patient. For a value-oriented (F in Myers-Briggs) volunteer, the doctor's attitude is more likely to be a crucial part of the whole experience. A sympathetic doctor could be the key to triggering the placebo effect in F volunteers regardless of the placebo itself. On the other hand, a 'too sympathetic' doctor could actually negatively affect the outcome for the more logic-oriented (T) volunteers.

Consequently, it seems that the combination of temperament and T/F characteristics in the study could help quantify and understand the necessary means to induce a placebo effect in all the volunteers and in patients in general. Have you conducted any such personality-correlated studies? Do you know of any such studies?

Regards, Beth Epstein

Leuchter's response:
You ask a very interesting question. Many people have attempted to correlate personality type, suggestibility, socio-economic status, or a variety of demographic factors with placebo response. These efforts have been disappointing; it appears that the tendency to respond to placebo is a characteristic widely shared by people. Your theory is very reasonable, and it would be interesting to examine specific temperaments and determine whether more sophisticated approaches using the MBTI would yield new insights. We now are using measures of temperament in our studies of depression.