Wonder drugs of the 1990s, Prozac and its kin have been prescribed
to tens of millions of people. But a growing backlash may portend the end of
Can Prozac make you want to die? The idea seems strange, given that the drug and
similar antidepressants are supposed to do just the opposite. Yet that is what
Kimberly Witczak believes happened to her husband. Two years ago Tim "Woody"
Witczak killed himself at age 37, soon after going on Pfizer's Zoloft—the
top-selling member of Prozac's class of drugs, known as selective serotonin reuptake
inhibitors, or SSRIs. Her husband was an upbeat, happy man, says Kim Witczak.
Shortly before his death he had been named vice president of sales at a startup
that sold energy-efficient lighting. When anxiety about the new job caused insomnia,
he was prescribed Zoloft. He began suffering from nightmares, profound agitation,
and eerie sensory experiences after a couple of weeks on the medicine—at
one point, she says, he said he felt as if his head were detached from his body.
Then he seemed to calm down. But about five weeks after his first dose, he hanged
himself from the rafters in their garage when Kim was out of town. He left no
"Woody's death was the most out-of-the-blue, out-of-character death,"
she told FORTUNE recently. "He had no history of mental illness."
Kim Witczak, who lives in Minneapolis, has sued Pfizer, alleging that Zoloft
induced the suicide and that the company failed to warn about the drug's potential
to cause perilous side effects. Pfizer declined to comment while the case is
in litigation, but a spokesman asserted that there is "no scientifically
based" evidence to suggest Zoloft can induce violent acts. It's not the
first time SSRI makers have faced complaints related to suicide or other forms
of violence. They have fended off or quietly settled scores of such suits over
the years without significant injury to their drugs' reputations.
But the Witczak case, which may play out in court next spring, is likely to
put SSRIs on trial as never before. For one thing, Kim Witczak has emerged as
a formidable crusader. Poised and articulate, she has appeared at congressional
and Food and Drug Administration hearings (most recently this month) to tell
of her tragedy and the dangers of SSRIs. What's more, her suit is likely to
spotlight disturbing information that drug companies and U.S. regulators have
been aware of for years—but that most doctors prescribing the drugs have
known little or nothing about.
Controversy about SSRIs' side effects flared into national prominence last
year when they and older antidepressants were shown to double the risk of suicidal
thoughts and behavior in children and adolescents. That discovery prompted the
FDA to slap a stern "black box" warning on the drugs' package inserts.
(Among other things, it cautions doctors to monitor young patients closely in
their first months on SSRIs.)
A black-box warning about suicidal thoughts and behavior in adults may very
well be next, say a number of experts interviewed by FORTUNE. "I'm fully
expecting that the same [risk found in young patients] will be found in adults,"
says Dr. Richard Kapit, an ex-FDA official who handled the agency's first safety
review of Prozac before its approval in 1987. (He now works as a medical writer
and consultant in Bethesda, Md.) In fact, last summer the FDA warned that several
recent studies suggest that SSRIs and other antidepressants raise the risk of
suicidal behavior in adults as well as kids. The agency added that it is reviewing
"all available data" on the issue in an investigation expected to
take a year or more.
Risk of suicide isn't the only problem dogging SSRIs. For example, GlaxoSmithKline
faces thousands of lawsuits on another side effect, severe withdrawal reactions
to its drug Paxil, one of the fastest-acting SSRIs. Last year British policymakers
moved to discourage the use of SSRIs to treat mild depression. And a recent
scientific analysis has challenged long-held assumptions about how the drugs
work. That could undercut drugmakers' assertions that SSRIs are well understood,
potentially increasing doubts about their safety.
A black-box warning for adults could have huge repercussions, vaporizing billions
of dollars of future sales, increasing pressure on policymakers to curtail direct-to-consumer
drug ads, and prompting a slew of lawsuits. It could also complicate drugmakers'
efforts to roll out new antidepressants to replace current ones as the drugs
go off patent. The ultimate fallout could well equal or exceed that from Vioxx,
the Merck painkiller whose saga of potentially lethal risks, dodgy marketing,
and damaging courtroom disclosures has given Big Pharma the look of an ethical
disaster zone. If so, it would add a sad twist to a tale in which so many people
have been helped.
Birth of a Blockbuster
Prozac and its kin have been one of 20th-century medicine's great success stories.
Since the debut of Eli Lilly's Prozac in 1988, the drugs have grown into an
$11-billion-a-year market in the U.S. alone. Nearly 150 million U.S. prescriptions
were dispensed in 2004 for SSRIs and similar antidepressants called SNRIs, according
to IMS Health, a Fairfield, Conn., drug data and consulting company—more
than for any other drug except codeine. Perhaps one out of 20 adult Americans
are on them now, making brands like Zoloft, GlaxoSmithKline's Paxil, Forest
Laboratories' Celexa, and Solvay Pharmaceuticals' Luvox household names. Though
they don't work for everybody—many people have gone off the medicines
because of side effects such as dampening of sexual response—they've done
more than any other class of drugs to spur psychiatry's substitution of pills
In fact, we're popping so many SSRIs that their breakdown products in urine,
gushing into waterways, have accumulated in fish tissues, raising concerns that
aquatic animals may be getting toxic doses, according to recent research at
The SSRI phenomenon began almost the minute Prozac appeared. Doctors embraced
the drugs because of a virtue that seems increasingly ironic: It's hard to commit
suicide by overdosing on SSRIs, so they are deemed safer to give to severely
depressed patients than are older, more acutely toxic antidepressants such as
the so-called tricyclics. Indeed, the drugs once seemed so benign that some
psychiatrists marveled about how they appear to violate the law of "conservation
of mood"—a seemingly universal pattern in which drug-induced emotional
lifts are always followed by crashes, resulting in no net gain. Such talk made
Prozac seem safer than coffee. That paved the way for massive prescribing by
general practitioners with no special training in complex mental disorders—in
recent years some 70% of SSRI prescriptions have been written by primary-care
Within three years of Prozac's launch, annual sales neared $800 million. Newsweek
put the pill on its cover —a green-and-white capsule floating against
a blue sky under a headline that hailed it as a breakthrough drug. Even healthy
people were asking for Prozac, the magazine noted. By 1993 the idea caught on
that SSRIs could transform lives—curing not only depression but also shyness,
low self-esteem, and compulsiveness. Major boosts for the fad came from Listening
to Prozac, psychiatrist Peter Kramer's eloquent bestseller, and from celebrity
endorsements. Recounting his fight with depression, Mike Wallace of CBS's 60
Minutes told Newsweek he expected to take Zoloft for the rest of his life.
But for all the glow about SSRIs, the drugs have been among the most controversial
in the history of medicine. Bitter disputes about side effects have seethed
for more than a decade, usually out of sight of the mainstream media—in
supermarket tabloids, on websites, and in professional gatherings of scientists,
regulators, and shrinks.
Rare, dangerous side effects of potent medicines like antidepressants often
emerge only after the drugs have been prescribed to millions of people for years.
But in the case of SSRIs, that is not the whole story. There are signs that
manufacturers have downplayed known risks of the lucrative drugs and that regulators
and doctors haven't been skeptical enough about them.
Even the theoretical basis for prescribing SSRIs is now in doubt. The drugs
have long been said to work by boosting a brain chemical called serotonin, correcting
a neural imbalance underlying depression and other ills. That makes them seem
the epitome of modern medicine—what could be safer than restoring a natural
balance? A growing body of studies casts doubt on the theory, however, according
to a provocative report this month in PLoS Medicine, an influential peer-reviewed
journal published by the nonprofit Public Library of Science. The report points
out that scientists have never really understood the drugs' effects in the brain.
Yet pharmaceutical ads still cite the serotonin theory as a major reason for
prescribing SSRIs—a case of mythmaking "comparable to the masturbatory
theory of insanity," says British psychiatrist David Healy, a longtime
SSRI critic. Drug company spokesmen counter that considerable scientific literature
supports the serotonin-imbalance idea.
A number of scientists have theorized that while boosting serotonin, SSRIs
indirectly inhibit another key neurochemical messenger called dopamine. That
means the drugs may actually create a perilous brain imbalance in some people.
What's more, there's some evidence that dopamine inhibition underlies several
of the rare, serious side effects linked to SSRIs. One is akathisia, a kind
of extreme restlessness that has been implicated in suicidal impulses—Witczak
believes Zoloft induced akathisia in her husband.
The possibility that SSRIs may occasionally induce deranged mental states conducive
to homicide has cropped up again and again in the news. While evidence supporting
that idea is scanty compared with data on the risk of suicidal ideas and behavior,
it isn't easily dismissed out of hand. Consider some of the testimony at the trial
this year of teenager Christopher Pittman, charged with murdering his grandparents.
Richard Kapit, the ex-FDA official, testified for the defense—he says he
felt compelled to come forward after reading about the case in the news. Kapit
told the jury that the teen was "involuntarily intoxicated" by SSRIs
when he shot his grandparents. Kapit added that he believes that Pittman, who
was being tried as an adult and who was ultimately found guilty, "didn't
have the ability to form criminal intent" when he committed the murders at
Many psychiatrists feel that stories about SSRIs' side effects should themselves
carry bold cautions against media hype. The risk noted in the FDA black-box
warning last year is limited: Suicidal thoughts and behaviors occurred in about
4% of youngsters on antidepressants (mostly SSRIs) in clinical trials, vs. 2%
of those taking dummy pills. That doesn't necessarily mean actual suicides occur
more often among SSRI takers—there's too little data to answer that question.
And the risk must be balanced against the fact that SSRIs help many people—no
one disputes that depression is a huge problem, and even some of SSRIs' harshest
critics concede the drugs can play a valuable role in treating it when prescribed
The uproar, in fact, may be hurting some patients without access to psychotherapy,
the main alternative to drugs. Since family doctors are now often afraid to
prescribe SSRIs to kids, more depressed young people than ever are probably
going untreated, says Gregory Simon, a psychiatrist and health-care policy researcher
at Group Health Cooperative, a Seattle HMO. Prescriptions of antidepressants
for patients 18 and under have plunged by 20% since the suicide issue hit headlines
in early 2004, according to NDCHealth, an Atlanta health-care information provider.
(Less than 5% of antidepressant prescriptions are written for youngsters.) Says
Jerrold Rosenbaum, psychiatrist-in-chief at Boston's Massachusetts General Hospital:
"Most of us [in psychiatry] think the number of patients harmed by failure
to treat [due to fear of SSRIs] is much higher than the number who are harmed
Of course, many top U.S. psychiatrists, including Dr. Rosenbaum, have worked
with drug companies to establish SSRIs as medicines of choice for treating depression.
Their views aren't universal in medicine—European authorities have long
been more skeptical about the drugs. Soon after the FDA approved Prozac for
marketing in December 1987, German regulators rejected it, partly because of
concerns that the drug increased the risk of suicide; they later approved it
but required Lilly to include a warning in the drug's package insert about the
possible need to prescribe sedatives to counter the risk. Last December, Britain's
National Institute for Clinical Excellence, which guides that country's health-care
policy, recommended that SSRIs and other antidepressants not be prescribed "for
the initial treatment of mild depression, because the risk-benefit ratio is
And in April the British House of Commons Health Committee issued a caustic
report that may give a preview of things to come in Congress. SSRIs have been
"indiscriminately prescribed on a grand scale," the committee concluded,
partly due to "data secrecy and uncritical acceptance of drug company views."
Further, industry promotions have "worked to persuade too many professionals
that they can prescribe [the drugs] with impunity" to treat "unhappiness
[that] is part of the spectrum of human experience, not a medical condition."
Though Congress isn't likely to buy into the stiff-upper-lip rationale, it may
put some very awkward questions about SSRIs to their makers and the FDA in coming
months. (Texas Republican Joe Barton and other Congressmen grilled FDA officials
for hours just before the agency put the black-box warning on SSRIs for kids.)
Drug marketers have been extraordinarily adept at selling SSRIs—even
to people who may not need them. Consider that the drugs, once limited to treating
major depression, are now prescribed for everything from shyness about peeing
in public restrooms to shopoholism. (Such uses aren't approved by the FDA, but
there's no law against doctors prescribing SSRIs and other drugs for "off
The explosive growth of the drugs' market is largely a story of clever branding
as makers of "me too" SSRIs sought to replicate Prozac's success.
Pfizer, for example, positioned Zoloft, launched in 1992, as a versatile antidepressant
that could also treat ills such as post-traumatic stress disorder. Glaxo targeted
Paxil, launched in 1993, at anxiety disorders such as SAD (social anxiety disorder,
or excessive shyness) and GAD (generalized anxiety disorder, or unremitting
angst)—ills that had received little attention before Glaxo began promoting
Paxil to treat them. Lilly countered by expanding Prozac's indications to include
PMDD (premenstrual dysphoric disorder, or very bad moods some women suffer before
their periods) and depression in children.
Indeed, to marketers, SSRIs have been the pharmaceutical equivalent of Play-Doh.
In a remarkably forthright 2003 article, Vince Parry, now a branding expert
at Ventiv Health, a Somerset, N.J., health-care marketing firm, waxed euphoric
about psychiatry's "ownable syndromes." Published in a trade journal,
the article laid out strategies "for fostering the creation of a [medical]
condition and aligning it with a product" like an SSRI. Wrote Parry: "No
therapeutic category is more accepting of condition branding than the field
of anxiety and depression, where illness is rarely based on measurable physical
symptoms." He cites Lilly's positioning of Prozac to treat premenstrual
woe as an excellent example of condition branding—the company reinvigorated
its aging antidepressant by repackaging it in a lavender pill, dubbed Sarafem,
for women with PMDD.
But blaming marketers alone for the SSRI fad isn't fair. Doctors, insurers,
regulators—and we eager pill-poppers—are co-conspirators. Cupertino,
Calif., resident Ada Spade, for instance, takes an SSRI for a condition that
even few psychiatrists know about: compulsive shopping. The problem started
about 15 years ago when she was in her 30s, she says. "I'd go to the grocery
store and find myself stopping at eight stores on the way to buy something in
every one of them. I just could not stop." She tried therapy, budgeting,
cash-only purchasing—nothing had lasting effect. Her life changed a few
years ago when she took part in a study at Stanford University Medical Center.
Funded by Forest Laboratories, it showed that 17 of 24 "compulsive shoppers"
given Celexa, an SSRI made by Forest, were greatly improved—they could
even visit malls without buying anything. "I learned from the study,"
she says, "that, yeah, something is a little wrong with me, but with medication
I can be okay."
For harried doctors faced with lots of patients complaining of depression,
anxiety, or compulsions, drugs billed as versatile and safe can seem a godsend.
Prescribing SSRIs "has almost become a way that physicians are regulating
demands on their time," says University of Pennsylvania psychology professor
James Coyne. "What happens a lot in primary care, though, is that people
on the drugs don't get adequate follow-up. About half the time they need an
adjustment in dose, which they often don't get," increasing the chance
of side effects.
That effectively means a double whammy of risk: It raises the odds that rare
patients vulnerable to dangerous reactions will get the drugs as well as the
chance that they will spin out of control unmonitored by doctors. Even when
patients are monitored, emerging suicidal tendencies are often missed, says
Jerome Vaccaro, CEO of PacifiCare Behavioral Health, a mental-health-benefits
manager in Santa Ana, Calif. "It's a 'don't ask, don't tell' problem,"
he says. "Doctors don't ask about it, and patients don't spontaneously
volunteer they're feeling suicidal." To SSRI critics, these nitty-gritty
considerations should have prompted sterner warnings years ago. Asserts psychiatrist
Joseph Glenmullen: "The problem is that when you give these drugs to a
large population, you can get lethal side effects."
Mother's Little Helpers
If one had to identify when the sea change on SSRIs started, April 2000 would
be a top candidate. That's when Glenmullen, a clinical instructor at Harvard
who also works for its student health service, published a book called Prozac
Backlash. Playing up SSRI side effects via scary patient vignettes, the book
has become to the drugs' bashers what Listening to Prozac was to their fans.
Glenmullen sipped tea recently at a Cambridge, Mass., coffee shop while laying
out provocative historical parallels for the rise and possible fall of SSRIs.
Drug fads in psychiatry, he says, have appeared "like clockwork"
in 30-year cycles. The first was cocaine elixirs, which doctors in the late
1800s prescribed for everything from depression to shyness. Freud bolstered
the fad by commending cocaine in influential papers. But by the 1920s, cocaine's
dangers had become clear, and amphetamines replaced it as psychiatric cure-alls.
In the late 1930s uppers like Benzedrine were even sold over the counter to
treat nasal congestion. After the dangers of amphetamines rose to the fore,
the pattern was repeated with barbiturates and later with habit-forming tranquilizers
such as Valium. (Remember "mother's little helpers," from the Rolling
Stones song in the 1960s?)
Each fad followed the same trajectory. The medicines were first hailed as wonder
drugs for major mental illnesses. Then general practitioners began prescribing
them not just for major problems but for all sorts of relatively minor maladies.
Next, scattered reports of serious side effects appeared. After 20 years or
so of use, sellers of the medicines could no longer plausibly deny the problems,
leading finally to sharply curtailed prescribing. Given that SSRIs' popularity
took off in 1990, Glenmullen predicts that "we're still five to ten years
away" from full disenchantment with them.
Very few doctors agree with his view that SSRIs are as problematic as, say,
amphetamines. But a number of his positions—such as the charge that drug
companies have selectively used clinical trial data on SSRIs to paint an overly
rosy picture of them—no longer seem radical. Says Group Health's Dr. Simon:
"The real scandal [about SSRIs] has been the failure to disclose data."
Take the revelations that led the FDA to impose the black-box warning about
prescribing SSRIs for kids. The story began in 2003 when FDA officials noticed
a curious thing while examining the results of a trial with youngsters on Glaxo's
Paxil: The company reported that substantially more kids had shown "emotional
lability" on the drug than on a placebo.
Emotional lability? When the officials asked what the term meant, Glaxo submitted
details showing that "almost all of these events related to suicidality,"
according to an FDA internal e-mail on the matter in June 2003. (Suicidality
is shrink-speak for suicidal ideas or actions; the e-mail was eventually made
public at a congressional hearing but got scant media attention.) The implication
of higher suicidality on Paxil "has us worried," the FDA's Dr. Russell
Katz noted in the message, which he sent to colleague Dr. Andrew Mosholder,
an expert on drug safety. Glaxo, he noted acidly, "has not proposed labeling
changes [on Paxil to reflect the discovery], and makes a feeble attempt to dismiss
the finding." Agency officials launched a massive reexamination of trial
data on antidepressants in children.
That inquiry turned up worrisome data on suicide-related risk—information
that caused internal dissension at the FDA. Just before an FDA advisory panel
hearing on the issue, the San Francisco Chronicle reported that senior agency
officials had forbidden Mosholder to go public with his findings on the risk.
The agency's top brass feared that the data, which were still tentative, might
discourage doctors from giving antidepressants to kids who needed them. But
the focus of criticism soon shifted back to Glaxo. In June 2004, New York Attorney
General Eliot Spitzer sued the company, alleging that it had fraudulently withheld
unfavorable data on youngsters treated with Paxil. (Glaxo, which asserts that
the lawsuit was "unfounded," settled by agreeing to post its clinical
results on the web.) Last October the FDA finally confirmed that the suicide-related
risk is real for a wide array of antidepressants and required the stern warning
on their labels.
Clean Bill of Health?
For years, FDA officials had reason to be perplexed. SSRI makers have long
maintained there's no reliable scientific evidence that SSRIs cause suicidal
or aggressive behavior. Other key factors, like mind-boggling medical complexity,
helped obscure the issue. For instance, depression itself can increase suicidal
thoughts and behaviors, which makes it extremely difficult to tell whether a
drug is to blame. Further, doctors have long believed that antidepressants sometimes
"energize" depressed patients before lifting their moods—potentially
making them more prone to enact their despair. But over the past 15 years critics
have amassed a small mountain of data that point to suicide-related side effects,
including reams of medical journal reports, internal FDA memorandums obtained
with Freedom of Information Act filings, and unpublished industry documents
pried out via discovery in lawsuits.
The commotion about suicide risks dates back to 1990, when Harvard psychiatrist
Martin Teicher and colleagues reported that six of their depressed patients
had developed "intense, violent suicidal preoccupation" soon after
starting on Prozac. The report sparked sensational media stories on the drug's
purported dangers. But studies soon made the case that Prozac is no more dangerous
than older antidepressants and possibly much safer. The scare was further deflated
by revelations that the anti-psychiatry Church of Scientology had helped promote
it. In September 1991, an FDA advisory panel concluded there was "no credible
evidence" that Prozac promotes suicidal or violent impulses.
A far less reassuring analysis had unfolded behind the scenes, according to
internal FDA documents. The documents were later obtained by attorneys representing
plaintiffs who sued Lilly, alleging that Prozac had triggered suicidal and violent
acts. Lilly has quietly paid an estimated $50 million-plus to settle more than
30 such suits, according to an investigation in 2000 by the Indianapolis Star.
"Any settlements were based upon business decisions," says Lilly spokesman
Dan Collins. "We do not comment on specific details regarding lawsuits."
A few months after Teicher's report, an FDA safety official wrote to his superiors
sharply criticizing a study Lilly had submitted to the agency in hopes of quelling
the suicide concerns. The memo's author, David Graham, is the same official
who made headlines last year by publicly lambasting the FDA's handling of Vioxx.
His 1990 memo about Prozac argued that Lilly's "analysis of suicidality
does not resolve the issue" because the company had excluded cases of patients
who weren't in the company's main clinical trials—Graham had access to
data from early Prozac studies that were separate from the ones the drugmakers
emphasized. "It can be argued that these exclusions are not justified or
appropriate," he wrote. This "apparent large-scale underreporting"
of patients with "treatment-emergent suicidality" meant Lilly had
not proved that Prozac and violent behavior are unrelated, he argued. Yet when
it came time for the FDA to conduct the crucial hearing in 1991, Graham's analysis
wasn't mentioned and Prozac was exonerated. The clean bill of health is well
deserved, Lilly maintains. "More than 54 million patients worldwide have
taken Prozac," says Collins; it's "among the most studied medications
in history," and its safety "is thoroughly documented."
Yet critics blame the FDA's response largely on coziness between the agency
and Big Pharma—and on senior officials' fear of looking careless. Says
Kapit: "There's definitely a reluctance by the FDA to come out and say,
'A drug we've approved is really dangerous.'" The problem is compounded,
he adds, by the fact that the FDA unit charged with monitoring drugs' post-launch
safety is subsumed under the FDA branch that oversees drug approvals. The drug-safety
office has no autonomy to go public with its findings. If it could, Graham's
analysis of the Prozac data might have come out as early as 1991. (The FDA did
not respond to repeated requests for comment.)
An Injection of Itching Powder
SSRIs' darkest side may be the suicide risk. But other adverse effects may
pose just as big a problem for drugmakers. In the mid-1990s, for example, horror
stories about SSRI withdrawal symptoms began circulating on the Internet, signaling
a controversy that is now nearly as bitter as the one about suicide. One of
its leading crusaders, Rob Robinson, a building contractor in Signal Mountain,
Tenn., recently organized a protest against GlaxoSmithKline at its U.S. headquarters
in Philadelphia. He held a boycott glaxosmithkline sign as he paced the sidewalk
in front of the high-rise building along with a handful of fellow protesters.
A rock climber of renown—Climbing magazine once put him on its cover—Robinson,
45, says his experience with SSRIs started in 1998. He had committed to do a
traveling exhibition on climbing, but the project stressed him out and interfered
with his sleep, so his doctor prescribed Glaxo's Paxil. After a few weeks on
the drug, Robinson says, "I felt calmer. I thought, 'That's good.'"
Quitting it after a half-year, though, "I started having what I now know
are withdrawal symptoms," he asserts, including muscle spasms, extreme
sensitivity to sound, and "horrible electric-shock sensations in my head."
He went back on Paxil to alleviate the symptoms. Eventually concluding he had
a drug dependency, he found a specialist who took him off the drug in 18 days.
That triggered severe symptoms that Robinson claims brought him to the brink
of suicide. "I finally opened a door at the far side of hell after about
18 months," he says.
Today Robinson runs a website on Paxil's risks and has sued Glaxo, charging
that it deliberately failed to warn about the drug's potential to cause severe
withdrawal symptoms. Some 3,000 similar suits against Glaxo have been filed
across the country over the past few years, says Karen Barth Menzies, an attorney
at Baum Hedlund, a Los Angeles law firm that has handled many SSRI-related suits.
Glaxo's drug has become the withdrawal issue's main lightning rod because it
washes out of the body more quickly than most other SSRIs. Hence the effects
of its absence in the brain can occur with literally dizzying speed. (Doctors
recommend gradually tapering doses before quitting to minimize such symptoms.)
The symptoms of SSRI "discontinuation syndrome," as psychiatrists
call it, include dizziness, headaches, nausea, lethargy, insomnia, irritability,
visual disturbances, movement disorders, and electric-shock sensations (known
as "electric head" on web chat groups about SSRIs).
Glaxo concedes that such symptoms may occur when people quit taking Paxil abruptly.
Discontinuation symptoms, a spokeswoman notes, can also occur with other medicines,
such as blood-pressure drugs. But she says allegations that Paxil is addictive,
or that Glaxo has tried to hide data on side effects, are groundless. Most discontinuation
symptoms, she adds, are "mild to moderate in intensity, resolve on their
own within two weeks, and seldom need corrective therapy." It remains to
be seen how well such assertions will play in a courtroom if the withdrawal
lawsuits, which are still in pretrial proceedings, aren't settled first.
The most consequential SSRI side-effects lawsuit on the industry's horizon,
however, appears to be the Witczak case against Pfizer—the one involving
the man who hanged himself after taking Zoloft. The symptoms Woody Witczak purportedly
experienced suggest the restlessness-causing condition called akathisia. It
was first linked to the antidepressants in the 1980s; critics like Glenmullen
assert that it is one of SSRIs' most dangerous side effects, in part because
it is rarely seen, hence easily missed, by general practitioners who prescribe
the drugs. Ironically, a former Pfizer researcher wrote one of the medical literature's
most detailed articles on the subject while working for the company. His report,
which appeared in the Journal of Psychopharmacology in 1998, states that SSRIs
"may occasionally induce" akathisia. The condition's name comes from
the Greek for "not sitting still," and its cardinal symptom is intense
jitters—a patient who has experienced the sensation compares it to an
intravenous injection of itching powder. Akathisia is so unbearable for some
depressed patients on SSRIs that they apparently feel "death is a welcome
result," according to the report.
An internal Pfizer memo on the akathisia report may backfire on the company. Obtained
by Kimberly Witczak's attorneys in pretrial proceedings, it makes the remarkable
statement, "This article is not suited for distribution to general practitioners,
but may be of interest to neurobiologically inclined psychiatrists." Was
Pfizer leery of scaring GPs away from Zoloft? Responds company spokesman Bryant
Haskins: "It's a bit absurd to allege that Pfizer thought the paper revealed
some serious health issue and [then] decided to keep the information hidden by
publishing it in a medical journal." He adds that the paper "makes crystal-clear
that the scientific basis for any causal connection between SSRIs and akathisia
is very weak."
The SSRI backlash is being fueled by people across the political spectrum.
Dr. Sidney Wolfe of the liberal watchdog group Public Citizen in Washington,
D.C., for example, has long argued that the drugs are overprescribed; conservative
activists such as Phyllis Schlafly have launched campaigns against prescribing
SSRIs and other psychiatric drugs to children based on mental-health screening
How the controversy will affect Big Pharma revenues and profits isn't clear,
though. Since generic SSRIs are now on the market (Prozac's U.S. patent expired
in 2001), drugmakers are racing to bring out new versions of antidepressants.
Concerns about SSRIs may help speed the transition to such pricier, patent-protected
alternatives, offsetting the controversy's fiscal fallout. Or the new drugs
could themselves be damaged by the skepticism that has besieged the industry.
The FDA's scrutiny certainly seems to have intensified. Last year Lilly launched
a successor to Prozac called Cymbalta. It's an SNRI, a class of drugs that has
been hailed as offering significant advantages over SSRIs, such as faster action.
(SNRIs are touted as targeting two different chemical messengers in the brain
instead of just serotonin, as SSRIs do.) A few months later Lilly dropped plans
to seek approval for the drug as a treatment for urinary incontinence in women.
Last July the FDA revealed in a public alert that "a higher than expected
rate of suicide attempts was observed" in clinical trials with incontinence
patients on Cymbalta. Increased suicide risks hadn't been seen in earlier trials
of the drug. (A Lilly spokesman says that the Cymbalta suicide-attempt rate,
while higher than the rate for the U.S. population, is "consistent"
with worldwide suicide rates.) Such problems may someday be resolved by genetic
testing. It could take the guesswork out of determining which patients a drug
might help and which it might hurt.
Waiting for her day in court, Kim Witczak appeared at another Washington, D.C.,
forum this month—an FDA public hearing on direct-to-consumer drug ads.
"Prescription drugs ... should not be treated in the same manner as cars,
soap, or fast food," she told agency officials. Safety has to be No. 1,
she added, and all serious side effects ought to be communicated "in a
clear, concise, and honest manner, not just those that won't scare people away
from thinking twice about taking the drug."
Witczak's comments sounded like points her attorney is likely to make to a
jury. But as a success formula for the post-Prozac era, transparency might be
just the prescription that pharmaceutical marketers need.