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Do psychiatric adverse events outweigh the potential metabolic effects of some drugs?
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Benefit should justify risk
That was the principal reason why I voted against rimonabant [at the FDA advisory committee meeting]. When evaluating medications within the FDA or in any other context, the question is always: How much benefit do you derive from the amount of risk that is there? There can be situations in which the risk is just overwhelming and the benefit is modest and there can be situations in which the benefits can be substantial and the risks low.
 Sid Gilman |
Personally, I would be willing to endure considerable risk in order to prevent a disease like cancer or Alzheimer’s from progressing. But, when it comes to weight loss, that is a very different situation. The problem we encountered with rimonabant was that the clinical trial evaluated people who were overweight and the researchers eliminated any participant with a previous history of depressive symptoms. Even having done that they nevertheless encountered a number of people who developed suicidal ideation while taking the drug. That led me and others on the panel to conclude that this is not a safe drug.
What we need is more basic science before approving a drug like this. The question is whether there can be a drug developed that would selectively block hunger while leaving the components of the limbic system, which have to do with mood, alone, so the drug does not induce depressive symptoms. That is the holy grail.
Sid Gilman, MD, FRCP, is the William J. Herdman Distinguished University Professor of Neurology Director at Michigan Alzheimer’s Disease Research Center Department of Neurology at the University of Michigan.
Weight loss may have association
 Steven R. Smith |
It is not entirely clear what role weight loss alone, independent of the mode of therapy, plays in psychiatric and psychosocial health and well-being. There are some indications from previous data sets that there may be some mood changes that go along with weight loss in the positive aspect — people feel better when they lose weight — but also some data that suggest there may be adverse effects in some individuals. Until the math on that particular topic is completely cleaned up I am going to have a general “I’m not sure’” sort of attitude.
There is a logical reason to think that these things are connected. As Occam’s razor would say, it is most likely the drug doing that but there is also a little dangling piece of information in the back of my mind that says weight loss itself may be associated with mood and/or cognitive changes and that literature is not entirely clear at this point in time.
A lot has to be put into context. We, as a society, still have a bias against fat people and a bias against obesity pharmacotherapy. Whether we like it or not, those kinds of biases come into play every time a physician has to decide how to treat a patient or respond to the question, “How do I lose weight?” We generally have this view of obesity that is a little bit schizophrenic, in the wrong sense of the term; we have expectations for managing obesity that we do not have for other chronic diseases.
Steven R. Smith, MD, is an Associate Professor and Director of the Inpatient Research Unit at the Pennington Biomedical Research Center in Baton Rouge, La.