John W. Williams Jr., MD, MHS; Cynthia D. Mulrow, MD, MSc; Elaine Chiquette, PharmD; Polly Hitchcock Noël, PhD; Christine Aguilar, MD, MPH; John Cornell, PhD
For other ACP-ASIM Clinical Practice Guidelines, see www.acponline.org/sci-policy/guidelines.
Grant Support: By the Agency for Healthcare Research and Quality, contract #290-97-0012. Dr. Williams is a recipient of a Veterans Affairs Health Services Research Career Development Award.
Acknowledgments: The authors thank Drs. Robert Badgett, Valerie Lawrence, W. Scott Richardson, and Madhukar Tirvedi, who contributed content to the original report on which this manuscript is based; the project staff with the San Antonio Evidence-based Practice Center; the 11-member technical advisory panel; and the peer reviewers who provided helpful suggestions that improved the manuscript.
Requests for Single Reprints: John W. Williams Jr., MD, MHS, Department of Medicine, Mail Code 7879, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900.
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Current Author Addresses: Drs. Williams, Mulrow, Aguilar, and Cornell: Department of Medicine, Mail Code 7879, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900.
Dr. Chiquette: 8000 Oakdell Way, #1508-3, San Antonio, TX 78240.
Depressive disorders are persistent, recurring illnesses that cause great suffering for patients and their families.
To evaluate the benefits and adverse effects of newer pharmacotherapies and herbal treatments for depressive disorders in adults and adolescents.
English-language and non-English-language literature from 1980 to January 1998 was identified from a specialized registry of controlled trials, meta-analyses, and experts.
Randomized trials evaluating newer antidepressants (such as serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and St. John's wort) that reported clinical outcomes were selected.
Two persons independently abstracted data that were then synthesized descriptively; some data were pooled by using a random-effects model.
Of 315 eligible trials, most evaluated antidepressants in adults with major depression, were conducted among outpatients, and examined acute-phase treatment. Newer antidepressants were more effective than placebo for major depression (relative benefit, 1.6 [95% CI, 1.5 to 1.7]) and dysthymia (relative benefit, 1.7 [CI, 1.3 to 2.3]). They were effective among older adults and primary care patients. Efficacy did not differ among newer agents or between newer and older agents. Hypericum (St. John's wort) was more effective than placebo for mild to moderate depression (risk ratio, 1.9 [CI, 1.2 to 2.8]), but publication bias may have inflated the estimate of benefit. Newer and older antidepressants did not differ for overall discontinuation rates, but side effect profiles varied significantly. Data were insufficient for determining the efficacy of newer antidepressants for subsyndromal depression, depression with coexisting medical or psychiatric illness, or depression in adolescents.
Newer antidepressants are clearly effective in treating depressive disorders in diverse settings. Because of similar efficacy, both newer and older antidepressants should be considered when making treatment decisions. Better information is urgently needed on the efficacy of newer antidepressants in patients with nonmajor depression and in special populations, including adolescents.
Table 1. Classification and Dosage Range of Antidepressants
Table 2. Treatment Trials of Newer Antidepressants and Herbal Remedies
Meta-analysis of placebo compared with newer antidepressants for major depression in adults.Nn
Meta-analysis of older antidepressants compared with newer antidepressants for major depression in adultsNn
Table 3. Dropouts
Meta-analysis of newer antidepressants for dysthymia in adults.N
Meta-analysis of hypericum (St. John's wort) for depressive disorders in adults.N
Table 4. Treatment Trials of Newer Pharmacotherapies in Special Populations
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Williams JW, Mulrow CD, Chiquette E, et al. A Systematic Review of Newer Pharmacotherapies for Depression in Adults: Evidence Report Summary: Clinical Guideline, Part 2. Ann Intern Med. 2000;132:743–756. doi: 10.7326/0003-4819-132-9-200005020-00011
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Published: Ann Intern Med. 2000;132(9):743-756.
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