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Which antidepressants are most effective?

The glut of antidepressant drugs on the market and the ads for them may have you – not to mention doctors –   wondering how to tell one from the other. But a new study sheds light on which ones may be most effective in battling the blues.

Topping the list of a dozen prescription antidepressants reviewed: Zoloft and Lexapro. Patients taking those drugs in trials were also the least likely to drop out. But because Zoloft, made by New York-based Pfizer, is now off patent and available in relatively cheap, generic form, it may be the better choice for patients starting antidepressant therapy, write authors of the study published today in The Lancet, who are from Italy, Greece, England and Japan.

The scientists reviewed 117 randomized trials – testing "new generation" meds called serotonin-reuptake inhibitors (SSRIs) that enhance the effect of that brain chemical – conducted between 1991 and 2007. The trials involved nearly 26,000 people, two-thirds of them women. Their findings: eight to 69 percent of patients in the trials responded to Zoloft and 51 percent to 69 percent of them responded to Lexapro, which is made by Forest Pharmaceuticals  in New York. (The study of Zoloft with an 8 percent response rate was small and unusual; most studies showed more than a 50 percent response.)

Reboxetine, a Pfizer antidepressant not approved for use in the U.S., was the least effective, with 49 percent to 56 percent responding to it, according to the analysis.

"We have not had a chance to review this study, so it would be inappropriate for us to comment at this time," Pfizer spokesperson Chris Loder told ScientificAmerican.com.

The comparisons are "a new gold standard of reliable information" for doctors prescribing the meds and the patients taking them, writes. Sagar Parikh, a psychiatry professor at the University of Toronto in a commentary accompanying the study.

"They're all at least moderately effective, so how do you choose? Rather than saying everything is equal [when] in fact everything is not equal, you can now tell the patient, 'Here are a few that are the best in terms of strength, and here are the ones that are lightest in terms of side effects," Parikh tells ScientificAmerican.com. "Are you more worried about side effects and willing to sacrifice the potential power of the drug if it's easier on you?' Those who want the ones that are a bit more powerful, they can use this information to choose that."

The trials each lasted an average of eight weeks; most people take the drugs for six months to a year, Parikh notes  The study did not examine withdrawal from the drugs.

Nonetheless, Parikh says the analysis is important because it was done without the financial backing of pharmaceutical companies, although a number of the authors have received funding from such companies in the past. The researchers also used statistical methods to take into account the problem of "positive publication bias," the tendency of drug-makers to publish and release only studies that show favorable results for their products.  In addition, he says, the review also compared studies that used similar doses.

An estimated 15 million Americans  suffer from major depression, according to the National Alliance on Mental Illness (NAMI). (In a 2007 book, sociology and social worker professors questioned whether depression is over-diagnosed.) Some 118 million antidepressant prescriptions were written during U.S. hospital and doctor's office visits in 2005 according to a 2007 Centers for Disease Control and Prevention (CDC) report.

Photo © iStockphoto/Randolph Pamphrey

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