The Downsides of Prozac
by Craig Lambert
Harvard Magazine
Like many others, Elizabeth Wurtzel ’89 and Lauren Slater, Ed. M. ’89—the authors, respectively, of Prozac Nation (1994) and Prozac Diary (1998)—suffered
“Prozac poop-out”: the drug’s mood-altering effects wore off and
depression returned. In fact, according to a 1995 study by associate
professor of psychiatry Maurizio Fava, Prozac wears off within a year
for about one-third of those who take it. “This is tolerance,” says
clinical instructor in psychiatry and University Health Services
physician Joseph Glenmullen, M.D. ’84. His new book, Prozac Backlash (Simon
& Schuster), documents not only tolerance, withdrawal syndromes,
and drug dependency, but a panoply of dangers linked to “Prozac-like
drugs”—selective serotonin reuptake inhibitors (SSRIs). “We now have
unequivocal evidence from a wide range of side effects that Prozac-type
drugs impair the normal functioning of the brain,” Glenmullen says.
SSRIs include Prozac, Zoloft, Paxil, Luvox, Celexa—trade names that invariably include an x or z
for drugs that are best known as antidepressants. But “calling them
that is misleading,” says Glenmullen, who notes that primary-care
doctors, not psychiatrists, write 70 percent of SSRI prescriptions.
SSRIs are now prescribed for anxiety, obsessions, substance abuse,
chronic pain, shyness, even “to feel ‘better than well,’” Glenmullen
says. “They’ve become all-purpose psychoanalgesics. People think they’ve
got to keep up with the Joneses, pharmacologically—if everyone at your
office is taking Zoloft to stay alert and work long hours, you’ve got to
have it, too.”
Prozac sales surged in the wake of Listening to Prozac, the
1993 bestseller by psychiatrist Peter Kramer ’70, M.D. ’76, who coined
the term “cosmetic psychopharmacology” and sang that with Prozac he had
seen “patient after patient become…’better than well.’ Prozac seemed to
give social confidence to the habitually timid, to make the sensitive
brash, to lend the introvert the social skills of a salesman.” Sales
also broadened as pharmaceutical houses developed what some are now
calling “a strategy of marketing diseases as an effective way of
marketing drugs. It’s a trend toward pathologizing daily life,”
Glenmullen says. He points to a psychiatric syndrome called “social
phobia,” a very rare disorder that a therapist might encounter once or
twice in a career—people so terrified of social contact that they may,
for example, avoid going to restaurants for fear of being seen eating in
public. “Over the last few years, psychiatrists have been inundated
with drug-company mailings that cite ‘experts’ renaming ‘social phobia’
as ‘social-anxiety disorder,’” Glenmullen says. “The Food and Drug
Administration [FDA] recently approved Paxil to treat social phobia. But
the mass media report this to the public as a treatment for shyness!”
The drug panaceas, however, may be illusory.
Rigorous studies have shown that the placebo effect accounts for most—at
least 64 percent, and perhaps much more—of SSRIs’ benefits.
Furthermore, in clinical trials, side effects often tip off research
subjects that they are getting the active drug. Better-designed studies
use placebos with side effects (like dry mouth), but no antidepressant
properties. Under these conditions, Glenmullen writes, the “performance
of the placebo climbs and the difference between the placebo and the
antidepressant is virtually washed out.”
What
is not washed out are the side effects, which include the potential for
brain damage. A few years ago one of Glenmullen’s patients who was
taking Prozac developed a tic—the tongue darting in and out of the
mouth—that persisted for months after the drug was discontinued. That
sent Glenmullen to Countway Library. He found reports of tics and other
neurological side effects, like drug-induced Parkinsonism, associated
with SSRIs. “The tics include lip smacking, lip puckering, fishlike
kissing motions, and pelvic thrusting,” Glenmullen says. “They are
involuntary, disfiguring, and can be very noticeable—and may persist
long after the drug is stopped. This is the dread side effect
in psychiatry, and it can indicate brain damage. Such reactions are not
rare. Neurologic agitation is estimated to occur in 10 to 25 percent of
patients, and muscle spasms in 10 percent."
The FDA mandates clinical trials for
antidepressants that typically last only six weeks and primarily test
the drug’s efficacy and short-term safety. “We lack systematic
monitoring of long-term side effects,” Glenmullen says, noting that a
former FDA head estimated that only 1 percent of long-term side effects
comes to the agency’s attention. Glenmullen adds that such side effects
of psychiatric drugs typically take three decades to gain a critical
level of attention, as with the restlessness and involuntary
twitching—tardive dyskinesia—associated with Thorazine and other major
tranquilizers. “Those drugs were prescribed the way Prozac is now,”
Glenmullen states. (To date, an estimated 30 million people have
ingested SSRIs.)
Earlier generations
of serotonin-targeting drugs like cocaine, amphetamines, diet pills, and
Ecstasy “have been exhaustively studied in animals, and all have been
shown to be neurotoxic to cells in the brain—for example, destroying
nerve endings. But there’s very little comparable research on the
SSRIs,” Glenmullen says. “To do animal research, you need tiny doses of
the pure drug. Yet researchers say that each pharmaceutical company
controls the supply of pure drug while it is under patent. To do studies
under a company’s auspices means signing a contract that allows it to
veto publication unilaterally."
Hence, side effects show up in the massive field
trial of the marketplace. “Repeated studies have shown that about 60
percent of patients have some form of sexual dysfunction—loss of libido,
difficulty reaching orgasm, impotence—on SSRIs,” Glenmullen says. “But
Eli Lilly’s official figure is 2 to 5 percent.” More ominously, the
Prozac “lift” has lifted some into violent rampages, like that of the
Louisville printing-press operator who in 1989 killed eight and wounded a
dozen more with an AK-47 assault rifle just weeks after starting
Prozac. Glenmullen has seen some of his own patients besieged by
suicidal thoughts of “a particularly obsessive quality” after starting
Prozac, and says that the Swedish and German equivalents of the Physician’s Desk Reference warn doctors of this potential side effect and provide guidelines for managing it.
For his part, Glenmullen has long prescribed Prozac and other SSRIs and
continues to use them in specific cases. But he also suggests numerous
treatment alternatives for anyone using or contemplating the use of such
drugs—including psychotherapy, cognitive therapy, behavioral treatment,
12-step programs, herbal remedies like St. John’s wort, exercise, and
diet modifications. About one SSRI user in four really does benefit from
the drug, he says, but he adds, “There is no free lunch. Most of these
people who feel so good about the long-term use of Prozac think it’s
cost-free. Patients need to be better educated about the risk-benefit
analysis. If they are taking Prozac to feel ‘better than well,’ that’s a
big mistake."
