It was called the "breakthrough drug for depression."

Boosted by a barrage of media attention, including cover stories in New York magazine and Newsweek, Prozac became the best-selling antidepressant in history in less than two years, bringing in an estimated 1 million prescriptions a month for its manufacturer, Eli Lilly & Co.

But into the life of a drug so successful, inevitably some rain must fall.

First came a report -- published in the American Journal of Psychiatry earlier this year by a Harvard researcher -- about six people who took Prozac and began fantasizing obsessively about killing themselves. Last month, a Long Island, N.Y., secretary filed a $150 million suit against Lilly, alleging that Prozac made her slash herself with razor blades, dig scissors and screws into her skin and attempt suicide repeatedly.

In the past month, more than half a dozen lawsuits have been filed against Lilly by people who claim that Prozac, known generically as fluoxetine, caused violent behavior.

One such suit, filed July 25, involves Joseph Wesbecker, a former press operator, who took Prozac. A Louisville lawyer contends that Prozac was the reason Wesbecker gunned down 20 of his former co-workers with an AK-47 before fatally shooting himself in September 1989. The suit, filed on behalf of three women whose husbands Wesbecker killed, asks Lilly for $150 million in damages.

Whether Prozac is responsible for these incidents is a matter of considerable debate. And even if Prozac can, in rare instances, cause an obsession with suicide, many psychiatrists say these problems are outweighed by the fact that the drug has fewer side effects and is more effective for some people than other antidepressants.

"Prozac is not a wonder drug," said Brian B. Doyle, a clinical professor of psychiatry and family medicine at Georgetown University School of Medicine. "It has side effects and some of them may be very serious. But I'm still very glad to have it available because it helps some people whom nothing else has helped, and many people find it easier to take than other antidepressants. When it works, it really works." Patient Testimonials

Some patients who have taken Prozac are enthusiastic about its effectiveness. They say the drug has worked where therapy and other medications have failed. "It has really made a difference in my life," said a 33-year-old Washington public affairs director, who has taken Prozac. The woman, who asked not to be identified, said she had been depressed since adolescence. Years of therapy and a trial of Xanax, a popular anti-anxiety drug, did not help much, she said.

"After a few weeks on Prozac, I realized my outlook on life was brighter," she recalled. "Since taking it, my friendships have blossomed, I've developed a couple of friendships at work that I never had before. I didn't know that I could look at life without seeing all the bad."

Lilly began marketing Prozac in 1988. Within months, it outpaced what was then the market leader, a drug called Pamelor, to become the top-selling antidepressant in the country.

Much of Prozac's initial success stems from the fact that psychiatrists have viewed it as much safer than other antidepressants, which have been associated with sluggishness as well as blood pressure and heart disturbances. The main side effects associated with Prozac are insomnia, nausea and anxiety -- complications doctors view as considerably less serious.

While other antidepressants have been linked to weight gain, Prozac has been associated with weight loss, an advantage for some depressed people. Another benefit is that the lethal level of Prozac is much higher than that of other antidepressants -- a major consideration in treating depressed patients, who have a greater risk of suicide and may be tempted to overdose on prescribed medication.

"When you make a decision about treating somebody with an antidepressant, you weigh the risks and benefits," said Martin Teicher, a researcher at McLean Hospital, a private psychiatric facility in Belmont, Mass., that is affiliated with Harvard Medical School. "If you have a medication in which there are no serious side effects and the possibility of benefit, then the risk-benefit analysis shifts so far in the opposite direction that you say you might as well try it. You have nothing to lose."

As word of Prozac spread, media interest in a new medication that relieved depression with few known side effects boosted the popularity of this latest "wonder drug."

"People came in asking to be put on Prozac, which is pretty amazing," said David M. Goldstein, director of the mood disorder clinic at Georgetown University Medical Center. "The response was phenomenal."

But as more people started taking the drug, side effects began to emerge. In February, Teicher and two others reported that six patients had developed intense, obsessive thoughts of suicide after taking Prozac. Two patients said they thought about buying a gun for the first time; another fantasized about killing himself in a gas explosion or car crash.

The study is crucial to the Kentucky lawsuit against Lilly -- and is at the heart of the debate over Prozac's safety. "It's a major piece of evidence," said B. Hume Morris, the lawyer representing the three widows. McLean is "a well-respected {hospital}, and the study seems well done," he said.

'Sweeping Conclusion'

But many psychiatrists say Teicher's report is limited and far from conclusive. For one thing, they say, the article is only a case report and not a formal experimental study. A more conclusive study, they say, would directly compare Prozac with a placebo and with other antidepressant drugs. "It doesn't make sense to reach a sweeping conclusion about a drug on the basis of a cluster of events," said Paul Leber, director of the FDA's division of neuropharmacological drug products.

Another criticism is that the few patients the report describes don't accurately represent the more than 2 million people who have taken the drug. Five of the patients described in the article had considered suicide in the past, and all had previously tried other antidepressants -- with mixed success. Critics also say that patients at a psychiatric hospital are probably not typical of depressed people, the majority of whom are never hospitalized.

"Marty's patients weren't your neighbors down the street on Prozac," said Jerrold F. Rosenbaum, chief of the Clinical Psychopharmacology Unit at Massachusetts General Hospital in Boston. "These are very atypical patients" who had tried other antidepressants without success and had been suicidal previously.

Teicher acknowledges that the report alone is not conclusive. But he said the study's findings are relevant because the type of obsessive suicidal behavior he observed in his patients "was unlike anything they had ever experienced either before or since. It really seemed to be something out of the expected pattern."

"Although the study is limited to six patients, it suggests this is a possible effect of the medication and that more research is needed," he added. "We wrote the article to say 'Please be aware of this and please let us know.' "

In May, Lilly revised Prozac's package insert to add that "suicidal ideation" -- violent behavior -- and pancreatitis, an inflammation of the pancreas, had been reported in some of those who took the drug. But company spokesman Edward West said there is no proof Prozac causes suicidal thoughts and adds that such thoughts have also been seen in people on other antidepressants, as well as in depressed people who aren't on any medication. "It's a phenomenon associated with the disease of depression," he said. "The risk of suicide in patients with depression is well documented."

West cites a survey Rosenbaum conducted shortly before Teicher's report was published. In that study, presented at this year's American Psychiatric Association meeting, Rosenbaum concluded that the percentage of patients on Prozac who developed suicidal thoughts was about the same as the percentage of those taking other antidepressants who developed such thoughts.

Drug-Induced Obsession?

Rosenbaum based that conclusion on a survey of 27 Massachusetts General Hospital-affiliated psychiatrists who had treated a total of 1,017 patients. He said the survey found a rate of suicidal thoughts of 3.5 percent for patients on Prozac, 1.5 percent for a class of antidepressants called tricyclics, such as Pamelor, 0 percent for a class called monoamine oxidase inhibitors, including Nardil, and 3 percent for other types of antidepressants. But Rosenbaum calls this difference "insignificant," because all of the figures fell within a statistical error margin of one another.

When Rosenbaum went back and reviewed the cases of the people in his survey who took Prozac and became suicidal, he didn't find any cases of the violent obsessive behavior Teicher observed. He also found that a higher number of the Prozac patients had severe personality disorders and were far more likely to think about suicide. This tendency may have helped skew the percentages of people on Prozac who were classified as suicidal, Rosenbaum said.

In fact, Rosenbaum said, obsessive suicidal thoughts have been seen with other antidepressants, such as some tricyclics. One theory is that these drugs can agitate some people who start thinking about suicide because it seems like a way to relieve their acute anxieties.

Nor does a consensus exist on whether Prozac triggered Wesbecker's murderous rampage. In their report on the case, the coroner's jury concluded that while Wesbecker had Prozac in his blood, along with lower levels of other psychiatric drugs, there was no definitive link between the drug and his behavior. The finding was issued last December, two months before Teicher's report was published in a psychiatric journal.

Even with Teicher's article, "it's going to be extremely difficult to prove in court that Prozac caused Wesbecker's rampage," said Richard Greathouse, the Louisville coroner who investigated the case. "You've got 2 million people taking Prozac, and out of that 2 million people you've got an isolated incident of violent behavior. What is there to say that Wesbecker would not have done this anyway?"

Teicher's report was what alerted the psychiatrist treating Rhonda Hala, the 40-year-old New York secretary who is suing Lilly, that Prozac might be causing her self-destructive behavior. But Hala's attorneys say the article is just one piece of evidence in their case.

They say that the number of adverse incident reports filed with the FDA by doctors who presribed Prozac for patients, combined with articles in other psychiatric journals and with Hala's experience, prove that Prozac caused her behavior. Hala said she was given the drug in late 1988 because she was depressed after she ceased taking painkillers following back surgery.

Eva Kemper, an FDA spokeswoman, said that as of Aug. 3, 8,900 adverse reaction reports about Prozac had been filed with the agency by health care workers. "This is not a large number of adverse reactions," said Kemper. "It compares favorably with other drugs of this type."

Prozac is expected to reap between $700 million and $800 million this year for Indianapolis-based Lilly, whose overall sales are projected to total about $4.7 billion. Lilly stock dropped by about $2 a share immediately after news of Hala's lawsuit, but analysts say part of this was due to a general downturn in the market.

"We're not changing our purchase recommendations or lowering any estimates," said Ronald Nordmann, senior drug analyst at Paine Webber in New York. Nordmann added that he doesn't think the recent bad publicity will affect Lilly's applications with the FDA to market different versions of the drug for weight loss and bulimia.

The lawsuits and a publicity campaign by the Church of Scientology, a Los Angeles-based group critical of psychiatry, allege that Lilly did not adequately test Prozac before it was marketed. They ask that it be taken off the market.

"Their clinical trial period was very brief, and they had no track record as to what the side effects would be with this totally new drug," said Leonard Finz, one of Hala's attorneys. "The fact of the matter is they either knew of the bad side effects or certainly should have known."

But both the FDA and Lilly say trials of Prozac were extensive. Lilly says about 6,700 people took the drug, some for as long as a year, before it was commercially available. "As far as I know, there were more individuals involved in that data base prior to the marketing of Prozac than for any other antidepressant approved by the FDA in the last decade," said the FDA's Leber.

Psychiatrists express mixed feelings about the negative impact the recent bad publicity about Prozac may have on prescriptions of the drug. Some say it may reduce the number of inappropriate prescriptions typically written for weight loss and for reactive depression, a type of sadness that is virtually universal after the death of a relative, a divorce or other traumatic life event. So far, Prozac has only been approved by the FDA for use in treating people with endogenous depression, an illness that is long-term and not caused by a sudden trauma.

Some psychiatrists say they're concerned that if nonpsychiatrists become less comfortable with Prozac, the drug will reach fewer of the estimated 10 million seriously depressed adult Americans. One advantage of the drug, they say, is that family practitioners have felt more comfortable prescribing Prozac over other antidepressants because the side effects associated with the medication were believed to be milder.

"The vast majority of depressed people in this country aren't treated by psychiatrists, nor will they go to psychiatrists, nor are psychiatrists available," said John Livingood, a psychopharmacologist affiliated with St. Elizabeths Hospital in Washington. "I don't think it's a bad thing" for the general practitioner to prescribe Prozac.

"I think the bad publicity is a natural rebound," he added. "The more popular something is, the more people are going to listen to you if you have something to tell about it."