Friday, January 28, 2011

What Do We Really Know about Depression?

A brief but valuable blog post:

--from SciCurious at the Scientific American blog offers some very valuable insights on the recent failure of the antidepressant reboxetine, as we previously reviewed:

What SciCurious adds to our understanding is that the failure of reboxetine is an even bigger setback for research and drug development than would be evident from the failure of a single drug. The problem is that based on everything you can do in the test tube and in lab rats, reboxetine should be the best antidepressant since sliced bread. It jumps thru all the hoops that scientists have long relied on to screen substances for possible antidepressant effects in humans. The fact that a drug passes all these tests and then doesn't work in humans means that the tests are now seriously called into question--as are the basic scientific theories of neurotransmitter function that the tests are based on. In a previous post I briefly alluded to Leo and Lacasse's excellent work in exposing the flaws in the serotonin theory of depression:

It now seems even more likely that we need to go back to the drawing board in figuring out what exact sort of "chemical imbalance," if any, depression really represents, and how that relates to finding better drugs for it. This example simply highlights what really hard work it is to find good new drugs. It's sad that an industry that used to be really good at finding these drugs seems so seriously to have gotten out of the business--as reviewed in the most recent post befoere this.


Bernard Carroll said...

Some will say that we harvested the low hanging fruit years ago so we should not be surprised that the pace of genuine innovation in antidepressant drugs is so slow today.

But the reboxetine example also points up the problem of relying on animal models of human psychiatric conditions. The validity of these models has never been established.

Years ago I coined Carroll's dictum: The model is not the disease.

Joseph P Arpaia, MD said...

Dr. Carroll has it correct. More generally, "the model is not the reality", whether that is in medicine, economics, or even physics.

Considering that there are dozens of known neurotransmitters, most of them peptides, few of which are understood, its surprising that anyone ever believed in the monoamine hypothesis.

In medieval times the theory was that all disease was caused by an imbalance in the four humors: blood, phlegm, black bile, and yellow bile. Treatment for disease was based on restoring the balance in these four humors.

Well modern psychiatry isn't even up to medieval standards yet. We have only three humors: dopamine, serotonin and norepinephrine. Treatment is based on restoring the putative imbalance in these three humors.

Powered rhinoceros horn anyone?

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Steve Scott said...

I have tried countless drugs to help me with my depression and I have been taking a Venlafaxine/Lithium augmentation for the last 4 years. Whilst this proved reasonably successful, in comparison to the previous drugs, my recovery after 30 years of clinical depression has been fuelled not by medication but changes to the way I think, feel and act. If the drugs are the answer, how is it I still have depressive periods from time to time? Nothing perceptible has changed but I now know that when these periods arrive I am far better placed to deal with them by the way I react to them, i.e. by not fighting it and by participating in things that make me happy. I have chronicled my journey from the darkest depths of despair and suicidal thoughts to recovery in my book, 'Insiders: Outsiders' and this provides a powerful incentive for others to stop relying on drugs and to make recovery happen themselves.