WSJ Science Journal: Some Drugs Work To Treat Depression, But It Isn't Cle

[question everything]

The Wall Street Journal

November 18, 2005

SCIENCE JOURNAL
By SHARON BEGLEY

Some Drugs Work To Treat Depression, But It Isn't Clear How
November 18, 2005; Page B1

Hardly any patients know how Lipitor lowers cholesterol, how Lotensin reduces blood pressure, or even how ibuprofen erases headaches. But when it comes to Prozac, Zoloft and Paxil, ads and glowing accounts in the press have turned patients with depression into veritable pharmacologists, able to rattle off how these "selective serotonin reuptake inhibitors" (SSRIs) keep more of the brain chemical serotonin hanging around in synapses, correcting the neurochemical imbalance that causes depression. There is only one problem. "Not a single peer-review article... support(s) claims of serotonin deficiency in any mental disorder," scientists write in the December issue of the journal PLos Medicine.

(snip)

Yet the evidence was always circustnatial. You can't measure serotonin in the brains of living human beings. The next best thing, measuring the compounds that seoertonin breaks dowon to in cerebrospinal fluid, suggests that clincally depressed patients had less of it than healthy people did. But it was never clear whether depression caused those low levels, or vice versa. A 2002 review of these early experiments took them to taks for such flaws. There had always been data that don't fit the serotonin-imbalance theory. Depleting people's serotonin levels sometimes changed their mood for the worse and sometimes didn't. Sending serotonin levels through the roof didn't help depression, a study found as early as 1975.

(snip)

A clue to how SSRIs do work comes from how long they take to have any effect. They rarely make a dent in depression before three weeks, and sometimes take eight weeks to kick in. But they affect serotonin levels right away. If depression doesn't lift despite that serotonin hit, the drugs must be doing something else; it's the something else that eases depression.

The best evidence so far is that the something else is neurogenesis -- the birth of new neurons. When scientists led by Rene Hen of Columbia University and Ronald Duman of Yale blocked neurogenesis in mice, SSRIs had no effect. When neurogenesis was unimpeded, SSRIs made the mice less anxious and depressed -- for rodents. As best scientists can tell, SSRIs first activate the serotonin system, which is somehow necessary for neurogenesis. That is what takes weeks.

(snip)


Write to Sharon Begley at [email protected]

URL for this article:
http://online.wsj.com/article/SB113226807554400588.html

[xchrom]

1. i've tried the prozac derivitives -- i couldn't take them.

they help some of my friends -- and don't work for others.