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Newer Antidepressant Drugs Are Equally as Effective as Older-generation Drug Treatments, Research Shows

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Press Release Date: March 18, 1999

Newer categories of antidepressant drugs are equally as effective as older-generation antidepressants and roughly equal numbers of patients drop out of clinical trials because of side effects, according to a new evidence report comparing drug treatments for depression. The evidence report was conducted by the San Antonio Evidence-based Practice Center on behalf of the Agency for Health Care Policy and Research (AHCPR). It found that selective serotonin reuptake inhibitors (SSRIs) are equally as effective in treating depression as older generation antidepressants, such as tricyclics.

"SSRIs are therapies of choice for many practitioners, but there are a lot of options out there and no particular class of drugs is routinely more effective than others," said Cynthia D. Mulrow, M.D., MSc, the study's lead investigator and a professor of medicine and geriatrics at The University of Texas Health Science Center at San Antonio (UTHSCSA).

The study found that both newer- and older-generation antidepressants have side effects. Patients taking the newer antidepressants were more likely to have higher rates of diarrhea, nausea, insomnia and headache. The older drugs were likely to cause adverse effects on the heart and blood pressure, and result in dry mouth, constipation, dizziness, blurred vision and tremors. While anecdotal reports suggest high rates of difficulty in sexual functioning, this report found little data that directly addressed this problem.

"The good news for the many people suffering from depression is that this rigorous analysis of the scientific literature has endorsed the effectiveness of a wide array of medication options, however the risks and benefits of these options must be carefully weighed," said co-author John W. Williams, Jr., M.D. "In the studies we analyzed, people dropped out of clinical trials for both older and newer antidepressants at similar rates because of drug side effects."

The study did not compare drug costs for the nine categories of antidepressants, the dosing schedules, nor the risk of various drug-to-drug interactions. The report was designed to provide a comprehensive evaluation of the efficacy of newer pharmacotherapies and herbal medications, such as St. John's wort, kava kava and valeriana, for depressive disorders.

"This analysis shows the importance of evaluating the evidence on the full range of treatments—new and old, conventional and alternative—so that clinicians have all the information available when making treatment decisions with their patients," said AHCPR Administrator John M. Eisenberg, M.D. "This type of broad-based, comparative analysis will be very useful to AHCPR's partners as they develop guidelines and other programs to improve the quality of depression treatment."

The literature review found no evidence of effectiveness of kava kava and valeriana, and concluded the that the evidence about the effectiveness of St. John's wort is unclear. However, compared to a placebo, the literature suggests that St. John's wort shows promise for mild to moderate depression, and may have fewer adverse effects reported than older generation antidepressants. The National Institutes of Health, through the National Institute of Mental Health, the National Center on Complementary and Alternative Medicine, and the Office of Dietary Supplements, is now sponsoring a placebo-controlled, blinded clinical trial comparing St. John's wort to a selective serotonin reuptake inhibitor.

The process for developing AHCPR's evidence reports is very different from the Drug Approval Process of the FDA. St. John's wort is not currently marketed in the U.S. as a drug product, and has not been shown to be "safe" or "effective" for treatment of any disease. AHCPR-sponsored evidence-based reports are taken from literature sources, and the products represented in these sources may not be representative of products currently being sold as dietary supplements.

A summary of the Evidence Report on Treatment of Depression—New Pharmacotherapies (AHCPR Pub. No. 99-E013) is available can be accessed online at Print copies are available from AHCPR Publications Clearinghouse by writing to P.O. Box 8547, Silver Spring, MD, 20907, or calling 800-358-9295 within the U.S., or (703) 437-2078 from outside the United States.

Final copies of the full report will be available in mid-1999 from both the Clearinghouse and the National Library of Medicine's HSTAT full text retrieval system. The Evidence Report on Treatment of Depression—New Pharmacotherapies also will be published in volume 34, number 4, of the Psychopharmacology Bulletin, a publication of the National Institute of Mental Health.

Note to Editors: For further details about the study and to request an interview with the authors, contact Karen Stamm, (210) 617-5300, ext. 4266.

If you would like to receive AHCPR's press releases by E-mail, sign up for our electronic mailing list on the AHCPR Web site. We will remove you from the fax list. If you would like to be removed from the AHCPR media list, contact Karen Migdail at or (301) 427-1855.

For additional information, contact AHCPR Public Affairs (301) 427-1364: Karen Migdail, (301) 427-1855 (

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