Long-term Effects of Antidepressants (SSRI's)

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."