Prozac's Good, Not Wonder Drug
By D. Goleman - NYT News Service

After listening to all the good news about the antidepressant Prozac, researchers are taking a more sober second look. A statistical analysis of 13 studies of the medication finds that it is no more effective than the older generation of antidepressants it has largely swept from the marketplace.

The study, published in the current issue of The Journal of Nervous and Mental Disease, was the first meta-analysis of all of the published, stringently controlled studies of the effectiveness of fluoxetine, the generic name for Prozac. It concludes that "fluoxetine produces modest effects, roughly comparable in magnitude to those of other antidepressants."

Meta-analysis is a statistical method for combining findings from many smaller studies into one large one, rendering a more accurate overall assessment of the effectiveness of a treatment than does any single study.

The average patient treated with fluoxetine had more improvement than 66% of those who received a dummy pill, or placebo. But meta-analysis of tricyclic antidepressants, which were widely used before the advent of Prozac, found equivalent or higher rates of effectiveness.

"Despite all the talk of this being a wonder drug, it doesn't seem to produce any better effects than other antidepressants," said Dr. Roger Greenberg, a psychologist in the department of psychiatry at the SUNY Health Center at Syracuse, who was the main author of the new report. "We're concerned that what's presented to the public is an exaggeration. "

Commenting on the new comparison of benefits, Dr. Stuart Yudofsky, chairman of the psychiatry department at Baylor College of Medicine in Houston, said: "It doesn't surprise me. The tricyclics have been extraordinarily effective in treating depression."

The new finding is in keeping with one of the few studies to compare fluoxetine directly with tricyclic antidepressants. A 1990 article in The Journal of Affective Disorders by Danish researchers found that tricyclic antidepressants were more effective in treating depression, though they had more side effects than fluoxetine. To be sure, psychopharmacologists recognize that people vary widely in their reactions to any drug; there are certainly many people with depression who are genuinely helped by fluoxetine.

Greenberg said: "Fluoxetine undoubtedly works for some people. The question is how well it works compared to other things."

Prozac works by altering the action of the neurotransmitter serotonin. Ordinarily when brain cells secrete serotonin to send a chemical message to a nearby cell, the serotonin is rapidly reabsorbed. This "reuptake" inactivates the serotonin, clearing the way for another chemical message.

Fluoxetine interferes with the reabsorption of serotonin, making it more available to brain cells. Prozac was the first of a new generation of "selective serotonin re-uptake inhibitors," or SSRIs. Others include Zoloft and Paxil.

Unlike earlier antidepressants, which are more scattergun in their action in the brain, the new class of drugs limit their action to serotonin, and so have fewer side effects.

This makes fluoxetine easier to tolerate, an advantage that has played an important role in its becoming the leading antidepressant in sales. Side effects of tricyclic antidepressants can include dryness of the mouth and eyes, sensitivity to bright light, blurry vision, constipation, anxiety, weight gain, night sweats, cardiovascular problems and, in men, trouble getting an erection or ejaculating.

But fluoxetine is not without side effects of its own. The most notable are edginess, nausea, insomnia, weight gain and sexual difficulties, both in reaching orgasm and, for men, in maintaining erections.

Greenberg suspects that the side effects may have played a role in inflating the reported effectiveness of the medication in clinical trials.

The report notes that the effects reported for fluoxetine were greatest in those studies where patients had most side effects. "It's paradoxical that the drug marketed for its low side effect profile seems more effective when it has the most side effects," Greenberg said.