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Prozac, Paxil, Zoloft and Depression

A new drug that’s been approved in Europe and South America for treating depression may provide a potent new weapon in combating this debilitating condition, researchers announced this week at the annual meeting of the American Psychiatric Association in Chicago.

Like the currently popular antidepressants — Prozac, Paxil, and Zoloft, the new drug, called reboxetine, affects pathways in the brain involving brain chemicals called neurotransmitters. But while the leading drugs work on a neurotransmitter called serotonin, the new medication takes a different approach, targeting a transmitter called norepinephrine. Research results from a number of countries suggest that this approach is at least as effective, and for some patients, more so.

According to Dr. Gerd Laux of Germany, reboxetine has proved “highly significant” in reducing depression in studies that included over 5,000 hospitalized and outpatient participants. The number of patients who stop taking the drug due to side effects, most commonly dry mouth, agitation, and urinary hesitancy, was similar to the number that stop taking other antidepressants — a little less than 10 percent.

In Spain, reports Dr. Jose Carrasco, reboxetine has been used with patients who don’t respond to other antidepressants, as well as in combination with other drugs. “However, it is progressively becoming a first-line treatment,” he stated, noting that between 10 and 20 percent of Spanish psychiatrists now prefer to start treatment with reboxetine.

Carrasco said that among more than 2,500 patients with major depressive disorder, 78 percent had no symptoms after eight weeks of treatment. He also pointed out that although 28 percent reported side effects such as dry mouth, constipation, and sleepiness during the first week, this number dropped to 10 percent by the eighth week, suggesting that side effects may clear up after a short period of time.

All of the researchers emphasized the positive effects of reboxetine on social function in depressed patients. “There is a strong sense that most of the patients who use this [drug] have improvements in social function,” noted Dr. Carlos Berlanga of Mexico. He reports that many patients returned to their pre-depression levels of social functioning. Laux of Germany, Carrasco of Spain, Dr. Roger Montenegro of Argentina, and Dr. Koen Demyttenaere of Belgium all reported significant improvements in this area in patients taking the drug.

Reboxetine may be particularly helpful for depressed patients who haven’t responded to other therapies, and for those whose condition is severe, noted several of the researchers. Demyttenaere of Belgium noted that for these patients reboxetine may be more effective than medications that target serotonin.

Demyttenaere explained that because reboxetine targets norepinephrine, it seems to work on different aspects of depression from the drugs that target serotonin. Drugs like Prozac and Paxil appear to be more effective against symptoms of anxiety and agitation, while reboxetine may improve motivation and drive, he said. He noted that some patients taking serotonin-targeting drugs complain of feeling detached, and reboxetine may alleviate this feeling.

Montenegro of Argentina, who is Secretary of Education for the World Psychiatry Association, said that reboxetine also appears safe and effective in patients over age 65. “We experienced a very good profile of action with very low side effects, and also rapid function, with a very good relief of symptoms after the first or second week.” Demyttenaere also noted that reboxetine appears to take effect faster than other antidepressants, and researchers from the United States suggest that the drug may be more effective than current antidepressants for elderly patients.

A common complaint among patients taking drugs that target serotonin is sexual dysfunction. Both Demyttenaere and Montenegro reported that reboxetine does not appear to have this side effect.

According to Gerri Schwartz of Upjohn, the company that hopes to market reboxetine in the United States, the company is doing two large additional studies in this country that they hope to complete by fall. When these are finished, the FDA is likely to approve the drug. So far, reboxetine is the only drug of its kind in this new class of antidepressants.

Editorial Commentary: The release of Prozac in the late 1980’s marked the beginning of a new era of antidepressants. Previous antidepressants were just as effective, but had more side-effects, and most importantly, were much more dangerous in an overdose. The earlier antidepressants were like shotguns, binding to many sites within the brain. Prozac seems to bind primarily to sites associated with serotonin, one of the actions of the older antidepressants. Reboxetine binds to another site affected by the older antidepressants, one associated with norepinephrine. Acquiring more specific compounds such as reboxetine provides more choices for patients suffering from depression. Like taste in movies and food allergies, there is wide individual variations in response and tolerance to antidepressants, and the more choices, the more likelihood of finding a good fit. In addition, it is probable that like most other psychiatric medications, reboxetine will prove to be effective in other conditions beyond depression.

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