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Title: DG DISPATCH - ECNP: Venlafaxine Relieves Anxiety Symptoms
URL: http://www.pslgroup.com/dg/13168E.htm
Doctor's Guide
September 23, 1999


By Cameron Johnston
Special to DG News

LONDON, UK -- September 23, 1999 -- The novel antidepressant venlafaxine HCl (Wyeth Ayerst, Effexor XL in Britain, Effexor XR in the rest of the world) might be the next new weapon in doctors' armamentarium to be used in the treatment of generalized anxiety disorder.

Speaking at the annual meeting of the European College of Neuropsychopharmacology (ECNP), being held in London, UK, this week, researchers presented data from five studies showing that venlafaxine, a selective noradrenergic reuptake inhibitor, relieved many of the symptoms of anxiety disorder to a significant degree.

Many primary care doctors are over-diagnosing anxiety, but under-diagnosing depression, said Dr. David Sheehan, a professor of psychiatry at the South Florida University College of Medicine, in Tampa, FL, with the result that the patients are often prescribed an anxiolytic, "with terrible outcomes."

Moreover, he said, for all the changes that have come about in the treatment of all mental disorders over the past 30 years, "we still haven't made much of a dent in the statistics."

"The truth is, we haven't done much in the way of new treatments over the past decade," he said. But that's all about to change."

In one study, patients who received a 75 mg/day dose of venlafaxine showed a 10 point improvement on the Hamilton-Anxiety rating scale. Those in the placebo group showed an 8-point improvement, which Dr. Sheehan said was "not trivial". However, those in the 150 and 225 mg groups showed a much more significant improvement - 11 and 12 points respectively.

Expressed another way, he said, those in the 225 mg/day group showed statistically significant improvements in six out of seven domains for the Hamilton rating score, and those in the 150 mg/day group had statistically significant improvements in two out of seven domains.

Although patients in the placebo group did show some improvement, their Hamilton-Anxiety scores leveled off by week 16 and stayed that way for the duration of the study. Those in the treatment groups improved rapidly throughout the first 10 weeks of the study, but continued to improve to 28 weeks, he noted.

In a study that compared venlafaxine 75 mg and 150 mg/day to buspirone 30 mg/day, buspirone proved to be no better than placebo, whereas both doses of the venlafaxine were statistically significantly superior to buspirone, producing a four-point improvement on the Hospital Anxiety and Depression scale.

Even when adverse reactions were considered, venlafaxine was superior. While a quarter of those in the 75 mg/day group experienced nausea during the first week of the study, this fell to less than five percent at the eighth week. Similarly, for those in the 150 mg/day group, one-third experienced nausea at the start of the trial, but this fell to eight percent at week eight.

While venlafaxine is, in fact, a serotonin and norepinepherine reuptake inhibitor, Dr. Sheehan speculated that part of its unique action might come from the fact that these compounds act at different "levels". "At lower doses, it appears that venlafaxine is active mainly as a serotonin reuptake inhibitor, while at higher doses, the norepinepherine kicks in, so it appears that at lower doses it works more like other SSRIs, in contrast to what we might expect. Similarly, if we go to very high doses - maybe up to 375 mg/day, you get some dopamine uptake inhibition, a small amount, but it is there, and there have been some suggestion that some anxiety and some major depressive disorders are related to dopaminergic problems."

The pooling of these study results make venlafaxine the most extensively studied antidepressant for the treatment of generalized anxiety disorder and it will be several years before its nearest competitor catches up in terms of the size and scope of the drug development program, Dr. Sheehan added.

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