5/15/2000 • Doctor lashes out in Prozac battle

By Richard A. Knox, Globe Staff

http://www.boston.com/dailyglobe2/136/metro/Doctor_lashes_out_in_Prozac_battle+.shtml

Dr. Jonathan O. Cole, a Harvard psychiatrist who was one of the first to
suggest that Prozac and similar antidepressants could precipitate suicide,
is now criticizing drug companies and the US Food and Drug Administration,
saying they are failing to take the problem seriously.

Cole made his complaint in support of a federal court lawsuit that claims
the drug Zoloft, a chemical cousin of Prozac, caused a 13-year-old Kansas
City youth to kill himself.

"I still believe our 1990 article was correct and it does happen," Cole
said of the alleged suicide-antidepressant link that he and other McLean
Hospital researchers first suggested a decade ago.

Although Cole had remained silent amid manufacturers' efforts to discredit
his research, the Boston psychiatrist said he was angered by the actions of
Zoloft's maker, Pfizer Inc., in fighting the lawsuit brought by the family
of Matthew Miller, the Missouri teenager.

The youth had been taking Zoloft for only a week when he hanged himself in
his bedroom closet on July 28, 1997. His parents insist he had never
displayed suicidal tendencies and had never been treated for behavioral
problems. They say the boy had been unusually restless and jumpy in the
days before his death - symptoms that Cole and other researchers say are
warning signs of alleged antidepressant-related suicides.

"Against this background ... There is a clear prima facie case that Zoloft
caused Matthew Miller to commit suicide," said Dr. David Healy, a British
researcher who is the family's chief expert witness.

Pfizer lawyers, calling Healy a practitioner of "junk science," are
asking Kansas City Federal District Court Judge Katheryn Vratil to disallow
Healy as an expert witness. Cole was recruited by the Houston law firm
representing the Miller family to vouch for Healy's scientific rigor.

Pfizer representatives say there is no credible scientific evidence that
Zoloft and related drugs precipitate suicide. Company officials did not
return telephone calls Friday seeking comment.

In the decade since Cole and Harvard colleagues first reported on early
cases of extreme agitation among people taking Prozac and related
antidepressants, use of these drugs - called selective serotonin reuptake
inhibitors, or SSRIs - has reached 84 million prescriptions a year.

The wholesale cost of SSRI prescriptions last year was $7 billion, a 15
percent jump from 1998, according to IMS Health, a Pennsylvania research
firm.

Moreover, US physicians are prescribing Prozac, Zoloft, and a related drug
called Paxil for ever-younger patients and for a broadening list of
disorders.

A University of Michigan researcher reported Friday in Boston that nearly 2
percent of North Carolina children ages 6 to 14 received SSRI drugs in
1998. A growing number of physicians are giving children prescriptions for
SSRIs along with stimulants such as Ritalin, the researcher said, despite
the absence of any studies supporting such use.

Dr. Jerry Rushton and his colleagues found that Prozac, Zoloft, and Paxil
are being used widely by children not only for depression, but for school
phobia, anxiety disorders, bed-wetting, eating disorders, and attention
deficit-hyperactivity disorder. Their study was presented at the annual
meeting of the American Academy of Pediatrics and the Pediatric Academic
Societies.

While manufacturers have been successful so far in deflecting criticism,
opponents say the tide may be turning, due to lawsuits, media reports,
books, and statements from prominent scientists such as Cole.

The Globe reported a week ago that Eli Lilly and Co., the maker of Prozac,
was aware more than a decade ago that suicidal thoughts occurred in as many
as 1 percent of patients who were given the drug in early trials.
Furthermore, the patent for a new form of Prozac, invented by physicians at
McLean Hospital in Belmont and scientists at Marlborough-based Sepracor
Inc., specifically mentions suicide as a possible side effect of the
original Prozac. Lily has embraced the new Prozac and plans to market it
within two years.

"I have seen patients and reviewed cases where an SSRI unmistakably
precipitated a driven preoccupation with suicide," said Cole, 74.

Such responses are unusual, Cole said, but they should be taken more
seriously by manufacturers and federal regulators. "It's a relatively
small problem, but it exists," he said in an interview.

The problem, critics say, is that infrequent adverse effects are magnified
when millions of people take a drug every day. "I sense the scientific
community is beginning to understand they made a mistake in concluding that
they could rule out suicide as an adverse effect" from SSRI drugs, said
Thomas J. Moore, a drug industry critic at George Washington University in
Washington, D.C.

Nobody knows how many suicides have occurred among the millions of people
who have taken SSRI antidepressants. Richard Ewing, a lawyer in a firm
representing the Miller family, said the FDA had recorded about 2,000
suicides between 1988 and 1997 that may have been related to the drugs, but
says the agency acknowledges that this is a small fraction of the probable
cases.

Healy, the British researcher, has estimated that as many as 50,000
suicides worldwide may be related to the drugs' use.

Cole cited two studies by Texas researchers in 1993 and 1995 suggesting
that about 1 in 200 patients reported having new suicidal thoughts while on
Prozac, while none did while taking an older non-SSRI drug.

This rate "sounds about right to me," Cole said. It's "rare enough to
make most physicians not notice the effect, but common enough to cause
serious adverse effects, such as death by suicide, in a few patients," he
said.

But Cole said no one has done the large-scale studies necessary to pin down
the frequency of SSRI-related suicides. Such studies are not easy to do,
since suicides are uncommon events even among clinically depressed people
and researchers must distinguish those related to the underlying depression
from those preceded by the extreme agitation, called akathisia.

"Although the manufacturers of SSRI drugs could and should have done these
studies, to my knowledge no manufacturer of an SSRI drug has ever done a
study where the primary outcome of interest was to measure ...
suicidality" that emerged during treatment, Cole said in a document filed
with the federal court Friday.

Cole also said an FDA advisory panel convened in 1991 to consider the
alleged SSRI-suicide link "never came to grips with the reality or
non-reality of the phenomenon."

But other researchers defend drug manufacturers and federal officials for
the way they have responded to studies suggesting a suicide link. These
include Dr. Anthony J. Rothschild of the University of Massachusetts
Medical School, who coauthored a 1991 study that the SSRI critics cite as
evidence of a suicide problem.

Rothschild and his colleagues administered Prozac to three patients who had
attempted suicide and found they developed severe agitation and suicidal
thoughts once again. Those symptoms subsided when Prozac was withdrawn or
when the drug was countered by one with calming effects, according to the
study.

But Rothschild said he thinks Eli Lilly and Co., Prozac's manufacturer, and
the FDA "adequately addressed" the concerns.

"The thing that disturbs me" about current SSRI critics, Rothschild said,
"is the tone that suggests there's almost a conspiracy to cover up
information and not do the right studies."