By ERICA GOODE
A new Government report on anti-depressants offers some conclusions that may surprise Prozac Nation, even if they are no surprise to researchers: Prozac and other drugs of its generation are not any better--or any worse--than older compounds in treating major depression.
The report also sounded a note of caution for physicians who prescribe new antidepressants for children, and for patients who are only mildly depressed: There has not been enough research to establish whether the drugs are effective in either case.
Psychiatrists who specialize in treating depression said the report, by the Agency for Health Care Policy and Research of the Department of Health and Human Services, would help put to rest assertions that the new drugs make older antidepressants obsolete, and the skepticism of those who insist that older drugs remain the "gold standard" for treating severe depression.
"Neither of those extremes is accurate," said Dr. Matthew Rudorfer, acting associate director for treatment research at the National Institute of Mental Health, who is familiar with the report. "The importance of this report is that when one actually looks at the scientific data, it's clear that in the effective treatment of depression, one has many options, all of which work. What can make the difference, therefore, is how well matched a given individual with depression is with a given treatment.
The report, which examined 32 drugs, including three herbal treatments, was based on a review and analysis of hundreds of clinical studies and reports of adverse drug effects. Using a statistical technique called meta-analysis, the researchers were able to draw conclusions more sweeping than any individual research project could.
All the newer drugs, the researchers found, were more effective in alleviating major depression in adults than placebo treatments. Fifty percent of severely depressed patients improved significantly on the antidepressants, compared with 32 percent of those given dummy pills. And the drug performed just as well as tricyclics, the older class of antidepressants.
An analysis of long-term studies, the report said, showed that newer antidepressants also are effective in preventing relapse in patients who have recovered from depression.
The most widely known new anti-depressants are the S.S.R.I.'s, or selective serotonin reuptake inhibitors, like Prozac. But the new generation of drugs also includes drugs like Effexor, Wellbutrin and Serzone, which have different effects on chemicals in the brain.
The newer antidepressants do have some advantages over older medicines, said Dr. John W. Williams Jr., an associate professor of medicine at the South Texas Veterans Healthcare System in San Antonio, and a co-author of the report. While both have side effects, patients taking newer antidepressants on the whole appear to find the side effects more tolerable, and are less likely to stop taking the medicines because of them, Dr. Williams said.
Still, compared with patients taking tricyclic antidepressants, the report found, patients on the newer drugs are more likely to experience diarrhea, nausea, insomnia and headache. Sexual dysfunction is a familiar complaint of patients taking S.S.R.I.'s, but only a small percentage of studies reviewed in the report mentioned the side effect, and the report's authors concluded that it was "reported too infrequently for reliable interpretation."
Tricyclics, the report noted, are more likely than newer drugs to produce dry mouth, dizziness, blurred vision and tremors.
S.S.R.I.'s are also significantly less lethal than tricyclic antidepressants, making them safer for depressed patients, who can run a high risk of suicide. "There appears to be less of a risk of completed suicide with overdose," Dr. Williams said.
And the newer drugs, which have a simpler dosing system and do not require periodic blood tests to monitor drug levels, are easier for general practitioners, as well as psychiatrists, to prescribe. A large proportion of prescriptions for the drugs is written by general practitioners.
Still, older drugs may be a better "match" for some patients because the side effects of any antidepressants vary from person to person. Some side effects may be less of a problem for some patients than others: A drug that has sedation as a side effect, for example, may actually help a depressed patient who is having trouble sleeping.
New antidepressants, in particular S.S.R.I.'s, are often prescribed by physicians for minor depression, Dr. Williams said, though there are no good estimates of how frequently this occurs. Nevertheless, the report's authors could find few well designed,controlled studies examining the effectiveness of antidepressants in minor depression, though some S.S.R.I.'s appeared in some studies to effectively treat "dysthymia," or chronic low-level depression that may last for years.
Similarly, the report found that there are few conclusive studies of antidepressants in very young patients, leading the authors to conclude that "data are insufficient to guide management of depression in children and adolescents."
Three herbal treatments--kava, valeriana and St. John's wort--received mixed reviews in the report. The authors found no controlled studies, and thus no evidence, for the effectiveness of either kava or valeriana. Several European studies, however, have found St. John's wort to be more effective in treating depression than placebos. Because patients in those studies suffered from different types of depression, however, and because the quality and strength of European preparations of St. John's wort differ from those available in the United States, the report's authors resisted coming to firm conclusions about the herbal medicine.
Dr. David Kupfer, chairman of psychiatry at the University of Pittsburgh School of Medicine and an expert on the treatment of depression, said that perhaps the best thing about the new antidepressants is that they have made more people aware that depression is a treatable illness.
"As the pharmaceutical companies continue to target their new compounds," he said, "it increases the recognition of depression, increases the likelihood that people are going to get treated and decreases the stigma."