Antidepressants Remain Popular But Often Disappoint Consumers

Antidepressants Remain Popular But Often Disappoint Consumers

First there was Prozac. Then came Zoloft, Paxil, Effexor and Celexa. Now the Food and Drug Administration is poised to approve what could be the next blockbuster in the enormous antidepressant market.

The arrival of Lexapro, made by Forest Laboratories Inc., is expected as early as this month, and many patients and doctors are eagerly waiting. "Everyone's going to want to try it on some patients," says Philip Muskin, a Columbia University psychiatrist. He explains: "You keep hoping that the next one is going to solve all of the problems."

But both science and past experience suggest that many people are bound to be disappointed. Though demand for antidepressants is huge and growing -- they are now the second-most prescribed drugs after anti-infectives, such as antibiotics -- the frustrating reality for many patients and physicians is that they either don't work very well or have intolerable side effects.

Few patients realize that half of the people who go on antidepressants stop taking them after three months. Add to that the fact that Lexapro is, in part, a marketing maneuver. It is nearly identical in its chemical make-up to Celexa, which Forest also makes. And Celexa works very similarly to the other top-selling antidepressants. But doctors and analysts expect demand for the new drug to be huge, partly because so many patients cycle through antidepressants.

Sibyl Shalo, 32 years old, ran through four different antidepressants between 1994 and 2000. They either didn't work well or lost their benefits over time. Now she's on Celexa, which improves her depression but also causes constipation, diarrhea and fatigue. "If this is the best I'm going to get, that's not such a good thing," says Ms. Shalo. So she's awaiting Lexapro. "Now there's something else for me to try," she says.

Even the most popular antidepressants on the market work on only about half of the people who try them. Though the medicines have been life saviors for some patients, as many as 30% of those who are clinically depressed aren't helped by any existing drug, according to Datamonitor PLC, a London market-analysis company. Moreover, all antidepressants can cause troubling side effects -- for example, 37% of patients on antidepressants experience sexual dysfunction, according to a recent study by Anita Clayton, a University of Virginia psychiatry professor.

Doctors typically say a patient should stay on a treatment for at least six months to stabilize the depression, says Martin Keller, who is leading a long-term study of depression for the National Institute of Mental Health. "Adherence to treatment is a major problem" that leads many people to relapse, says Charles Nemeroff, chairman of psychiatry at Emory University School of Medicine in Atlanta.

The National Institute of Mental Health estimates about 19 million Americans -- 1 in 10 adults -- suffer from depression at some point each year. About half of them, eight million people, used antidepressants last year, according to Datamonitor. If you count those who used the drugs to treat anxiety, such as panic disorder, as many as 10 million Americans may have taken the medications in 2001.

Antidepressants became a staple of modern medicine with the introduction of Prozac in 1987. It was quickly followed by a string of similar drugs that all act by raising the level of serotonin and other chemicals in the brain.

Looming Competition

Forest is expected to lose FDA-granted exclusivity rights to Celexa as early as 2004, which could open it up to competition from cheaper, copycat versions. It's common for drug companies to try to fend off competition by bringing new versions of old products to market. But Lawrence Olanoff, Forest's vice president for scientific affairs, says the company made a conscious decision to develop Lexapro based on pre-clinical evidence that it worked better.

In clinical trials involving 1,321 patients, 59% of those who took Lexapro showed a 50% improvement in their depression after taking the drug for eight weeks, Forest says. In contrast, 53% of patients taking Celexa experienced the same level of improvement, compared to 41% on a placebo. Participants received a smaller dose of Lexapro -- either 10 milligrams or 20 milligrams each day -- than the standard 20 mg or 40 mg per day of Celexa.

But the company is most excited about what it says is a low incidence of side effects with Lexapro. In one study, published in the Journal of Clinical Psychiatry in April, 4% of patients taking 10 mg of Lexapro per day stopped taking the drug because of side effects, a result considered statistically the same as the 2.5% dropout rate for the placebo.

But at the higher dose of Lexapro (20 mg per day) the side-effect profiles of the old and new drug don't look very different. Indeed, 10% of patients on the higher dose of Lexapro stopped taking it, which is statistically the same as the 9% who dropped out on 40 mg per day, the higher dose, of Celexa. (Psychiatrists note that clinical trials in depression have often underestimated the side effects.)

Lexapro isn't the only new antidepressant on the horizon. Eli Lilly & Co., the maker of Prozac, hopes to bring a successor drug to market at the end of this year. Called Cymbalta, it may produce different results because it acts by elevating levels of a chemical in the brain called norepinephrine, as well as serotonin. Many of the newer antidepressants, including Lexapro, raise only serotonin levels.

Another Drug to Try

John Williams, a Honda salesman living in Seattle, enrolled in a Lexapro trial after finding he couldn't tolerate the loss of sexual appetite he suffered taking Paxil. On Lexapro, the sexual side effects almost entirely disappeared and he felt he could handle the others -- ringing in his ears and a spacey feeling in the morning.

When the clinical trial ended in April, he had to go off Lexapro, but began taking the closest thing on the market, Celexa. "They seem to be identical," he says. But while the drugs diminish his depression and anxiety, his symptoms aren't gone.

And so Mr. Williams is already wondering what new treatment is coming. His doctor just told him about a trial for yet another antidepressant starting soon, and he says he's thinking about enrolling.

Write to Geeta Anand at geeta.anand@wsj.com¹

Updated June 12, 2002