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Second-generation antidepressants equally effective

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Widely prescribed second-generation antidepressants all work equally well, a new study finds. Side effects -- including dizziness, insomnia, nausea, sexual-performance problems and weight gain -- also do not appear to differ significantly among this group of drugs, which includes such brand names as Paxil, Prozac, Wellbutrin and Zoloft.

In the Sept. 20 issue of The Annals of Internal Medicine, researchers report that patients' outcomes were overall similar, regardless of which second-generation antidepressant they had been prescribed. In light of these findings, the researchers suggest that deciding which drug is best may boil down to cost.

"The bottom line is that the comparative evidence on the newer drugs is that there is very minimal differences in efficacy between one and the other," says study author Richard Hansen, an assistant professor of pharmaceutical policy and evaluative sciences at the University of North Carolina at Chapel Hill. "So, given that there are 10-plus of the newer agents on the market, it's really difficult to say which is best, aside from the fact that there are tremendous cost differences."

One side effect that the researchers did not address -- the possible link between suicidal thinking/behavior and antidepressant use -- prompted the Food and Drug Administration in March 2004 to put black box-label warnings on many of these newer drugs, particularly in reference to children. After published reports pointed to the possibility of the same risk in adults taking antidepressants, the agency issued a second warning this summer that applies to adults.

However, the authors of this latest report note there were reasons why they did not deal with the suicide issue.

"I will emphasize that we did not feel strongly enough about the evidence that we reviewed to draw any conclusions on suicidality," Hansen says. "One of the primary reasons for that was that the information that has been reviewed that led to the FDA's decision for putting that warning on all secondary-generation antidepressants was derived from information that is not publicly available.

"These were studies that were submitted by pharmaceutical companies to the FDA," he says. "They were not published in the peer-reviewed literature, and some of the information comes from an analysis that I believe was done in the U.K. by the National Health Services, where they used pool data from published and unpublished studies -- where again we did not have access to the unpublished data -- where they found significant risk with certain drugs.

"A second point on suicide in the randomized, control trials and some of the prospective observational studies that were reviewed is that the way that suicide or suicidal behavior was classified really differs between studies," Hansen says. "So it's difficult to say that suicidal issues or behaviors are greater with one drug than with another when we weren't confident enough about how the researchers characterized or classified those behaviors to draw a parallel between those studies."

Available since the late 1980s, this newest generation of antidepressants works by inhibiting the activity of neurotransmitters such as serotonin and norephinephrine, which scientists believe play a part in the onset and progression of clinical depression. These selective serotonin-reuptake inhibitors -- known as SSRIs -- and selective norepinephrine-reuptake inhibitors have largely replaced the first generation of antidepressants, which are equally effective but more likely to produce side effects.

To assess the differences between all the second-generation antidepressants, Hansen and his team reviewed 46 studies conducted between 1980 and early 2005. The researchers also looked at an additional 24 noncomparative studies, which had observed the benefits of a single second-generation antidepressant, in some cases relative to a placebo.

Among the studies analyzed, the benefits of six SSRIs had been compared or observed: citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil) and sertraline (Zoloft). Four non-SSRI second-generation antidepressants were also assessed: bupropion (Wellbutrin), duloxetine (Cymbalta), mirtazapine (Remeron) and venlafaxine (Effexor).

All the drugs had been used in the initial treatment of patients suffering from major depression. Most of the patients were between 18 and 60 years old, and most of the studies in which they had participated had been sponsored by a pharmaceutical company that manufactured one of the medications.

On basic measures such as speed of patient response and quality of life improvements, the drugs were found to be more or less equally effective. In terms of side effects, the results were also similar across the class of medications, although some differences were evident.

The researchers noted, for example, that some trials indicated that nausea and vomiting were higher for venlafaxine than for other drugs. Dizziness was also most commonly found among patients taking this medication.

Mirtazapine, paroxetine and sertraline demonstrated a tendency to provoke higher rates of sexual side effects in several studies, while others noted that bupropion appeared to have one of the lowest rates of sexual side effects. Weight gain appeared to be most prevalent, on average, among patients taking mirtazapine, while headaches and insomnia were most commonly reported among patients treated with bupropion.

However, the study authors caution that, although differences in the incidence of side effects existed, they were minimal. And they add that wide disparities in the way side effects had been assessed among the studies made it difficult to draw any strongly negative conclusions about any one drug.

The researchers also stress that results that indicated slight benefits of one drug over another had to be taken with a grain of salt, because studies with some sort of connection with a drug manufacturer tended to slightly favor that company's drug over a competitor's.

Dr. Lorrin Koran, a professor of psychiatry and behavioral science at the Stanford University School of Medicine in California, says that the study should raise awareness of the comparative value of the most widely used antidepressants.

"The second generation helps some people that wouldn't have been helped, they have better side-effect profiles and some of them have fewer drug-interaction problems," Koran says. "So the advantages are clearly there."

c.2005 HealthDay News

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