More on Suicide---Facts, Opinions, Experience, and a little bit of Nonsense

In the NYT, there is an article by Gina Kolata, one of the best science writers in the business.  The title is: Why Test Animals to Cure Human Depression?  Ms. Kolata has picked up on the issue of antidepressants possibly causing suicide, and posed some interesting questions to some of the people who do research in the area of drug development.


OF MICE AND MEN

Why Test Animals to Cure Human Depression?

By GINA KOLATA

Published: March 28, 2004

YOU might think if questions were raised about whether antidepressant drugs can make patients suicidal during the first few weeks of treatment, that scientists would turn to animal testing for further investigation.

After all, suicides are rare enough that there are no firm human data on whether the drugs can cause them. But you can do experiments with animals - examining their brains, giving them high doses of drugs - that you could never do with people.

That might seem like a reasonable course of action, especially after the Food and Drug Administration announced last week that it was so concerned about a possible, though very slight, suicide risk that it wants antidepressant drugs to carry warnings on their labels. But it turns out that animal experiments are not an option.

The reason, said Dr. Alan Schatzberg, chairman of the department of psychiatry and behavioral science at Stanford University's School of Medicine, is that "we don't have an animal model of depression."

[...]Those symptoms, he noted, involve the prefrontal cortex, a brain area not highly developed in animals. So, he asked, "How do you model it in an animal?"

[...] Some psychologists say they can make animals exhibit signs of depression by putting them in situations where they feel helpless to control their fate. "All this stuff about animals don't feel sad or hopeless, that's some huge leap," said Dr. Martin Seligman, director of the Positive Psychology Center at the University of Pennsylvania. He said that the only sign of depression that could not be elicited in animals was suicide.

What if, by chance, researchers stumbled on an animal test that predicted whether an antidepressant drug might prompt suicide as a rare side effect in people?

"We would immediately go back and test all of our drugs," Dr. Ruffolo said. If the animal tests indicated that the drugs were linked to suicide, he added, the company would use the test to search for other drugs that were not.  [...]

Ms. Kolata points out that one of the difficulties in doing research on suicide is that it happens infrequently in the context of a research study.  Suicide is the 11th leading cause of death  in the USA, but that amounts to only 1.3% of all deaths per year.  In 2001 there were 30,622 deaths by suicide (or that were ruled to be due to suicide) out of almost 300 million people.  This means that, each year, about 0.01% of people will die via suicide. 

After a suicide, the most important question is: why did the person do it?  Obviously, it is very difficult to get the answer to that question, since you can't ask the only person who really knew.  Suicide notes, when they are found, may not always give the real reason.

The only definitive way to study an aspect of human behavior is by doing a randomized, double-blind, controlled, prospective experiment.  Nobody is going to do a study in which people are knowingly exposed to a risk of suicide, so there never will be a definitive study of the causes of suicide.  For similar reasons, I think there never will be an animal model for suicide risk.  If someone developed a putative animal model, it would only be useful if validated.  In order to validate it, you would have to demonstrate that the behavior of the animals is correlated with the behavior of humans.  

To complicate matters further, drugs can be associated with an increased suicide risk even if they are not psychiatric medications.  Accutane and interferon have been associated with suicide, and they have no known direct psychotropic effects.  As a result, it is difficult to postulate a model pathophysiology for suicide risk.  Without an idea about how, on a molecular level, a drug could promote suicide, there is little basis for establishing an animal model. 

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The F.D.A., Antidepressants and Suicide Risk (3 Letters)

Published: March 28, 2004

o the Editor:

Re "Regulators Want Antidepressants to List Warning" (front page, March 23):

There is much to be lost and little to be gained by the new Food and Drug Administration warning. It is true that there have been suicides by adults who happen to be taking antidepressants. But information about these suicides is based only on anecdotal reports, not scientific studies, and we know few details.

Do they involve people suffering from bipolar disorder who become manic when given antidepressants indiscriminately by general practitioners? Are these people using street drugs concomitantly and not telling their internists?

Unfortunately, the F.D.A. warning will scare many people away from taking a medication that would otherwise lead them to have happier and more rewarding lives. Rather than preventing suicides, this warning will create the risk of more suicides.

PETER KUDLER, M.D.
New York, March 23, 2004

To the Editor:

The Food and Drug Administration, with good intentions, has overreacted and opened the floodgates of fear and malpractice litigation ("Overprescribing Prompted Warning on Antidepressants," news article, March 24).

It would be ironic if this action caused patients to abruptly discontinue their medication out of fear and misunderstanding, which could trigger severe rebound depression, withdrawal and suicide.

Imagine the trial lawyers licking their chops ready to blame every suicide not on the disease but on the therapy. The F.D.A. has acted irresponsibly and foolishly.

MITCHEL L. GALISHOFF, M.D.
Valley, Ala., March 24, 2004

To the Editor:

The current brouhaha over antidepressants (front page, March 23) is another example of the medical profession's refusal to understand depression as a serious medical illness. Many internists dispense antidepressants to depressed patients and blithely instruct them to return in six months, as if they were treating a common allergy.

This practice is encouraged by managed care companies to rein in costs. Yet for the last 40 years, psychiatrists have known that depressed patients are at great risk for suicide in the earliest stages of recovery.

JUDITH EBENSTEIN, M.D.
Irvington, N.Y., March 24, 2004

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See this post  for a thoughtful, personal account of the appearance of suicidal thoughts after starting an antidepressant.

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Category: Things found while looking for other things
Subcategory: WTF???

Do you suppose the FDA should put a warning label on feminists?