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Lexapro: Anti-Depressant May Not Be Cure-All

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By LAURAN NEERGAARD, AP Medical Writer

Starting next week, psychiatrists will be able to prescribe an eagerly awaited new anti-depressant called Lexapro. It's being promoted as more potent and possibly safer than older competitors — but there's little evidence that it's much better.

Still, Lexapro promises to be a big player in the $12 billion anti-depressant market. So how do patients and doctors choose whether to try it or another of the bewildering array of depression drugs?

"You're playing the odds," is the blunt way Dr. Philip Ninan of Emory University puts it: Each anti-depressant comes with a different set of pros and cons, and there's little way to know in advance which will work best for which patient.

While patients today have better drugs than ever to fight depression, a huge swath of the 19 million Americans afflicted at some point in their lives fail to get relief. Experts estimate up to half of patients who try an anti-depressant stop altogether or switch to another within three months. Some can't handle the side effects; others get little or no benefit — likely because there are different causes of depression that require novel treatments.

Today's medications emphasize balancing brain levels of the feel-good neurochemical serotonin. Ninan is excited about a radically different approach, targeting hormones believed to cause patients with depression to have exaggerated responses to stress. But it will take years more research to prove if these experimental "CRF antagonists" fulfill that promise.

With potential breakthroughs so far away, any new option causes excitement — even if, like Lexapro, the drug isn't very different chemically from its predecessors. Indeed, Lexapro is a fine-tuned version of the popular drug Celexa, the latest in the Prozac-spawned class of "selective serotonin re-uptake inhibitors," or SSRIs.

Lexapro is "not God's answer to this illness, but it is a step forward," Ninan says. "The word I'd use is an incremental advance."

Forest Laboratories Inc., maker of both Celexa and Lexapro, argues that even an incremental advance means Lexapro can make a meaningful difference. So when Lexapro hits pharmacy shelves Sept. 5, the company will virtually end its Celexa marketing — meaning few if any free samples anymore — in favor of Lexapro, which will sell for 5 to 10 percent less than its roughly $2-a-pill predecessor.

"We're arguably taking a little bit of a gamble on this, but we believe we have a better drug," says Forest vice president Dr. Lawrence Olanoff.

Why? Celexa consists of molecules with mirrored halves. Only the left-hand side is believed to enhance brain serotonin levels; the right side is thought to be inactive or perhaps linked to some side effects. Lexapro is Celexa cut in half to get the presumed good side.

The Food and Drug Administration ( news – web sites) cautions that Lexapro hasn't been proved superior to any anti-depressant. But in a 491-patient study, 10 milligrams of Lexapro once a day worked as well as 40 mg of Celexa. A few patients felt better about a week sooner than Celexa users. And while Lexapro causes the same side effects seen with most SSRIs — from nausea and sexual disfunction to insomnia and daytime fatigue — about 5 percent fewer Lexapro users experienced them.

But there are numerous other choices, and psychiatrists advise considering dosing, side effects, even prices:

_SSRI granddaddy Prozac, for example, is available as a cheaper generic and as the only once-a-week anti-depressant. Even the once-daily version stays in the body longer than any other SSRI, possibly good if the patient skips pills but not if they take other medicines that can interact with Prozac, says Dr. Christopher Colenda of Michigan State University. The SSRI Paxil, conversely, clears out of the body so fast that patients suffer side effects if they quit cold turkey.

_The SSRI alternative Serzone helps balance serotonin through a different brain mechanism, meaning fewer sexual and sleep-related side effects. The trade off is occasional liver toxicity.

_Effexor targets both serotonin and the similar brain chemical norepinephrine, and thus is popular when SSRIs fail. Wellbutrin also affects both brain chemicals, although not as powerfully; it carries a risk of seizure.

_Depression often is accompanied by other mental health problems so look for drugs that have more than one effect. Luvox, for example, is an SSRI sold to treat obsessive/compulsive disorder; Paxil also treats anxiety.

And Colenda says always ask how other relatives with depression fared on different drugs, because a new patient will likely fare similarly.

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