As the National Alliance for Research on Schizophrenia & Depression in Great Neck, N.Y., pointed out, mood disorders are caused by a flaw in chemistry, not character. That‘s why medications that alter brain chemistry play a large role in their treatment.

There are now five prescription drugs in the class known as selective serotonin reuptake inhibitors -- or SSRIs -- approved in the United States for the treatment of depression, obsessive-compulsive disorders, bulimia nervosa, anxiety, panic disorder and other medical conditions such as PMS.

This raises the question: Does any member of the class provide better symptom relief or reduce serious or long-lasting side effects in treating these conditions?

James‘ Experience

James L. Smith, a 40-year-old high school teacher in Pontiac, Mich., has experienced bouts of depression since he completed college in the mid-1980s. His family doctor initially prescribed a �ricyclics antidepressant for him, but he found its side effects troublesome. "The medication made me tired and I had a difficult time sleeping," he said. "Basically, I just stopped taking it after about three months. I decided I‘d rather live with the depression."

By the time James sought help a second time, SSRIs had become available. "The psychiatrist I saw explained there was a whole new group of medications that were very good," Smith said. "If one didn‘t help after several months, he would prescribe another one. I assumed that meant they weren‘t identical; that one might work better than another for me. But that wasn‘t necessary. The first SSRI prescribed has worked well for more than five years."

How Do They Work?

According to the Encyclopedia Britannica, serotonin -- also known as 5-Hydroxytryptamine or 5-HT -- is a chemical that naturally occurs in the human brain, intestines, blood platelets and mast cells. Interestingly, it is also a component of many toxic venoms, including those of the wasp and some poisonous toads.

The chemical is derived from tryptophan, a natural amino acid. As a neurotransmitter, one of serotonin‘s most important functions is the transmission of impulses across synapses, the space between neurons or nerve cells.

Typically serotonin is concentrated in two specific areas of the brain -- the midbrain and the hypothalamus. These areas are responsible for regulating mood, hunger, sleep and aggression. Changes in the concentration of serotonin in these areas are linked to a variety of mood disorders, particularly depression.

Serotonin levels are thought to be reduced to below optimal levels when it is returned (or taken up) too quickly or in too great a quantity by neurons after the chemical has transmitted an impulse across a synapse.

All SSRI medications function by prolonging (or inhibiting) the process by which serotonin is taken up by neurons (the process referred to as "reuptake"). All SSRIs are designed to prolong the reuptake process only for serotonin. To differentiate between serotonin and a host of other chemicals in the brain, they must be highly selective.

That‘s how the class came to be known as "selective serotonin reuptake inhibitors" -- they prevent (inhibit) serotonin (and only serotonin) from experiencing too much or too long of a reuptake process. This makes more serotonin available in the brain. According to Sheldon H. Preskorn, M.D., professor and chair of the department of medicine and behavioral sciences at University of Kansas School of Medicine, Wichita, and author of Applied Clinical Psychopharmacology, SSRIs are effective for a significant number of individuals who use them as directed for this purpose.

The SSRIs‘ Pedigree

SSRIs weren‘t the first prescription antidepressants. That distinction goes to iproniazid, a member of the antidepressant class known as monoamine oxidase inhibitors (MAOIs).

Ipronizid was discovered accidentally in the early 1950s when the tuberculosis patients for whom it was prescribed experienced not only improvements in their tuberculosis, but also in their mood and activity levels. Later in the decade, the first antidepressant in the �ricyclics class, Imipramine (Tofranil), was found to have good results for depression, although it had been originally developed as a treatment for schizophrenia.

It took almost 30 years for researchers to unravel enough of the brain‘s functioning to understand that MAOIs and tricyclics probably work by promoting increases in the levels of certain brain chemicals, such as serotonin and norepinephrine. Then the search was on for medications that could do this selectively, that is, increase one of the chemicals responsible for improved mood, but not all of them at the same time.

The first SSRI to be approved by the U.S. Food and Drug Administration was Prozac in 1987; the most recent was Celexa in 1998. The five SSRIs presently approved for use in the United States are:

fluvoxamine maleate (Luvox) manufactured by Solvay

paroxetine (Paxil) manufactured by Smith Kline Beecham

sertraline (Zoloft) manufactured by Pfizer

citalopram (Celexa) manufactured by Forest Laboratories

fluvoxetine (Prozac) manufactured by Eli Lilly

In December 2000, Forest Laboratories announced the development of a "new generation" SSRI called escialopram, along with plans to submit it for FDA approval in early 2001. The newest potential member of the class is described on the manufacturer‘s Web site as a "form of Celexa" that may be more effective and have fewer side effects.