SUMMARY- A case study that linked the popular antidepressant Prozac to suicidal tendencies has opened the gates to lawsuits. Many psychiatrists worry that despite a lack of clinical evidence that Prozac causes people to become violent, an overdose of litigation could spell the end for an effective and worthwhile drug.

A 29-year-old mother of two small children in Florence, S.C., prepares a roast, starts making gravy and sets the table for dinner. When the family arrives for the meal, the woman is not in the kitchen. Her husband finds her hanged by a belt in a bedroom.

According to lawyers for the family, this woman was a victim of the controversial drug Prozac, which she had been taking to combat postpartum depression before she died in August. Marketed as an antidepressant, Prozac causes some depressed people to become violent or suicidal, critics say. "One does not make a roast and then make gravy and then set a table expecting everyone to have dinner and then go upstairs and commit suicide in this horrible manner," says Leonard L. Finz, who heads a New York law firm

specializing in product liability cases.

Finz says he is getting ready to file a lawsuit on behalf of the South Carolina woman's family, whose name he declines to reveal until he gets his case on file. It is one of hundreds of suits he says he is preparing against the drug's Indianapolis manufacturer, Eli Lilly and Co.

Approved by the Food and Drug Administration in December 1987, Prozac has captured 20 percent of the antidepressant market, has treated more than 3 million people in 45 countries and is expected to gross $1.1 billion for Lilly this year.

But the capsule that Newsweek magazine featured splashily on its cover last summer as a "miracle drug" with few of the unpleasant side effects of older antidepressants has found its way into the police beat stories

of newspapers as a "miracle defense" in murder cases and as a purported cause of suicide. The best-known example of violence that some have linked to Prozac was a September 1989 shooting spree in a Louisville printing plant in which former employee Joseph Wesbecker, who was taking the drug at the time, killed eight persons

and then himself.

About 70 civil lawsuits over Prozac have been filed against Lilly in state courts across the country. Most accuse the company of failing to test the drug properly before releasing it and of not warning physicians that a small percentage of people could become suicidal or violent. Lending credence to these allegations, lawyers say, are some 12,400 reports of adverse effects on file with the FDA,

including self-mutilation, suicidal obsessions and homicidal thoughts.

But there are few clinical studies supporting these allegations. Furthermore, depression can be an inherently fatal disease. One out of every six severely depressed people commits suicide. That means lawyers must prove that Prozac, not the depression it is supposed to treat, was the culprit in a death.

Russell Waddell and Dan Fontaine, two Houston attorneys specializing in product liability cases, say they got 73 calls from people seeking their services after a story was published about their client, Michael Morris, whose wife committed suicide while on Prozac. Because Prozac claims appear hard to prove, the lawyers have decided to take only three cases involving people whose medical histories showed no suicidal behavior and only mild depression before taking the drug.

The case of Susan Skye Morris fits the bill, Waddell says. She was 33 when she married Michael in Austin in September 1989 and moved to Houston. She had experienced previous bouts of minor depression and, separated from family and friends, she became depressed again. Last June she consulted a doctor, who prescribed Prozac. Within a week she was acting hostile and had quit her job with the Houston office of a state agency she had been with for years.

Suspecting the drug was to blame, she stopped taking it and was soon back to normal, Waddell says.

But by August her depression had returned , and on her doctor's advice she went back on Prozac. On Sept. 7 she took a lethal dose of other drugs and curled up in bed. Her husband did not realize she was dead until the next morning.

Waddell and Fontaine say they hope to get Lilly to court quickly. They have filed the case in Harris County's Probate Court, which oversees decedents' estates, because that court does not have the case backlog of the county's regular trial court. The suit seeks punitive damages for Lilly's allegedly reckless release of the drug. A victory on this claim

could provide a blueprint for similar lawsuits elsewhere, Waddell says.

What gave rise to the suits was a case study published in the American Journal of Psychiatry 14 months ago in which Dr. Martin H. Teicher of the Harvard Medical School observed

six patients who were depressed but free of suicidal tendencies. He noted that they developed "intense, violent suicidal preoccupation after two to seven weeks" on Prozac. Two other case studies show similar results.

But researchers have not explained how Prozac, whose chemical name is fluoxetine hydrochloride, could cause such behavior. The drug works on a neurotransmitter in the brain called serotonin, low levels of which are often found in people who commit violent acts. Prozac maintains high levels of serotonin in the synapses for a longer time. Flooding the brain in this way shuts down the brain's own production of serotonin, resulting in low levels that trigger aggressive behavior, says Bethesda, Md., psychiatrist Peter Breggin, a longtime critic of drug and shock treatments for the mentally ill.

"This should have set off terrible red flags at Eli Lilly," says Breggin, who will be an expert witness in several of Finz's cases.

Some antidrug activist groups, including the Citizens Commission on Human Rights, an offshoot of the Church of Scientology that earlier battled against prescribing the stimulant Ritalin to hyperactive children, want a ban on Prozac. The Public Citizen Health Research Group, a division of consumer activist Ralph Nader's organization, would not go so far, but wants Lilly to attach a warning to the label advising that some users have exhibited violent or suicidal behavior.

"Prozac appears to be very useful for people for whom nothing else has worked," says Public Citizen researcher Ida Hellander.

What concerns Public Citizen, she says, is overprescription: Although Prozac was designed to treat clinical depression, some doctors who are not psychiatrists prescribe it for mild depression and eating disorders, even for patients who want to quit smoking. Doctors like the drug because it is not as easy to overdose on as other antidepressants and it lacks such unpleasant side effects as sedation, weight gain and constipation.

In response to Teicher's article, the FDA issued an internal memorandum last summer concluding that suicidal preoccupations reported by some Prozac patients were not unusual or unexpected. The agency concluded there was "no basis to conclude that the use of Prozac is associated with any unreasonable or unexpected risk." FDA spokesman Eva Kemper will not comment on the pending lawsuits.

Lilly also refuses to comment on the suits. Marie Abbott, a spokesman for the company, says the results of 15 years of research at Lilly before the drug went on the market do not support Teicher's findings. After Teicher raised the issue of suicides, she says, Lilly researchers looked back through their data and studied 3,000 randomly selected patients who had participated in clinical studies. "We found serious suicidal tendencies were less" among Prozac users than among those on placebos or other antidepressants, she says.

Lilly, with assets of $21 billion, has made it clear

that it will not settle lawsuits. Ronald Nordmann, a drug industry analyst for PaineWebber Inc., says the controversy has barely dampened Lilly's sales. Prescriptions for Prozac are at 90 percent of the rate last July, before the lawsuits started.

Most psychiatrists still support Prozac, although some are asking patients to sign informed consent waivers. "It's the only drug in my practice that people have come in asking to take," says Dr. John Dluhy, a Washington psychiatrist.

John Blamphin, director of public affairs for the 37,000-member American Psychiatric Association, says, "Prozac is one of many drugs available to psychiatrists for the treatment of depression. It's not the best drug for all patients, but it's a good drug. There's no reason to push the drug off the market."

A flood of lawsuits over Prozac could do just that, doctors fear, despite the lack of clear scientific proof that the drug

prompts suicidal and violent behavior. They point to the example of Bendectin, an antinausea drug taken by more than 30 million pregnant women between 1956 and 1983 but pulled from the market that year amid an avalanche of lawsuits alleging it caused birth defects. Its manufacturer, Merrell Dow Pharmaceuticals Inc., spent $120 million fighting 1,300 suits and winning virtually all of them. The Bendectin experience led pharmacologists to doubt

whether any company will ever again risk introducing a drug for morning sickness.

In a few instances the federal government has stepped in to keep "unavoidably unsafe" but largely worthwhile drugs on the market by offering immunity to manufacturers. In 1976 the government agreed to be the sole defendant in lawsuits arising from swine flu vaccinations after drug companies refused to produce the vaccine. The government also started directly administrating damage awards over the DPT vaccine that prevents whooping cough. The vaccine saves an estimated 150,000 lives each year but also causes central nervous system damage in a handful of cases.

However, mere approval by the FDA is not a foolproof shield for a manufacturer. In a holding typical of those in most states, New Jersey's high court ruled in 1984 that manufacturers are liable for damages if a jury finds that an FDA-approved drug contains "avoidable" defects. In a case with a similar issue, the U.S. Supreme Court agreed last month to decide whether federally required health warning labels protect cigarette companies from lawsuits filed by people who claim they were

not properly warned about the hazards of smoking.

Over the past decade manufacturers have been trying to persuade Congress to pass a law outlawing punitive damages when an FDA-approved drug hurts someone. Victor E. Schwartz, a Washington tort defense lawyer who drafted a proposed Product Liability Fairness Act, says it is "preposterous" to expect manufacturers to come out with new drugs while damage awards skyrocket and liability laws differ from state to state.

But such a bill would not absolve drug companies from paying compensatory damages. That leaves plenty of room for Finz and other attorneys to weave a case against Lilly by dramatizing to juries the personality differences in alleged Prozac victims before and after taking the drug. Says Finz: "These kinds of violent deaths are not the kind of suicides that a person contemplates, except if that person does not have control of what that person's doing. They are typical Prozac fingerprints."

Photo (color), The drug has won 20 percent of the antidepressant market since its 1987 approval., By Jon A. Rembold/Insight Photo (color), Finz is preparing hundreds of suits. Photo (color), Morris killed herself while on Prozac.