John W. Williams, MD, MHS; Cynthia D. Mulrow, MD, MSc; Elaine Chiquette, PharmD; Polly Hitchcock Noël, PhD; Christine Aguilar, MD, MPH; John Cornell, PhD
Williams JW, Mulrow CD, Chiquette E, Noël PH, Aguilar C, Cornell J. 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.
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.
indicates number of participants; indicates number of studies. GABA = γ-aminobutyric acid; HT = hydroxy-tryptophan; RIMA = reversible inhibitor of monoamine oxidase A; SSRI = selective serotonin reuptake inhibitor; SNRI = serotonin and noradrenaline reuptake inhibitor.
. indicates number of participants; indicates number of studies. HT = hydroxy-tryptophan; MAOI = monoamine oxidase inhibitor; NRI = norepinephrine reuptake inhibitor; RIMA = reversible inhibitor of monoamine oxidase A; SSRI = selective serotonin reuptake inhibitor; SNRI = serotonin and noradrenaline reuptake inhibitor; TCA1 = first-generation tricyclic antidepressant; TCA2 = second-generation tricyclic antidepressant.
indicates number of participants. *Response rates not given. HT = hydroxy-tryptophan; SSRI = selective serotonin reuptake inhibitor.
indicates number of participants. The diamonds represent a summary estimate, derived from the individual studies listed above the diamonds. The center of each diamond is the point estimate, and the tails represent the 95% CIs.
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