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Newer and older antidepressants are equally effective for treating major depression in adults, but side effects differ

Major depression is estimated to be the fourth most important cause of worldwide disability. In fact, the lifetime risk for major depressive disorder ranges from 10 to 15 percent for women and 5 to 12 percent for men. Newer antidepressants and readily available herbal remedies have led to wider but sometimes confusing choices for doctors treating patients with depression. A recent study may help guide these choices. [Editor's Note: It is important to note that psychotherapy continues to be a treatment option for major depressive disorder, although this study did not deal with it.]

For this study, researchers at the Evidence-based Practice Center (EPC) at the University of Texas Health Science Center did a meta-analysis of 315 randomized trials comparing newer antidepressants such as serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and St. John's wort to placebo and to older tricyclic antidepressants.

The 6- to 8-week long studies were done on adults with acute major depression (at least 2 weeks of depressed mood or loss of interest or pleasure in nearly all activities, along with loss of appetite and/or difficulty concentrating or making decisions) or dysthymia (chronic mood disorder with depressed mood on more days than not for at least 2 years with two or more symptoms such as loss of appetite, insomnia, fatigue, or difficulty concentrating). Overall, 51 percent of those receiving newer antidepressants compared with 32 percent who received placebo improved (at least a 50 percent reduction in depressive symptoms). Efficacy did not differ among newer agents or between newer and older agents (54 percent of patients receiving either agent reduced symptoms by least 50 percent). Hypericum (St. Johns wort) was more effective than placebo for mild to moderate depression, but publication bias may have inflated its benefit.

Also, 59 percent of dysthymic patients who received either an older or newer antidepressant improved compared with 37 percent on placebo. Newer and older antidepressants did not differ overall in terms of the number of patients who stopped taking their medication, but side effects (e.g., diarrhea, nausea, insomnia, blurred vision, constipation) varied significantly depending on the drug class. Because they are similarly effective, both newer and older antidepressants should be considered when making treatment decisions, according to Cynthia Mulrow, M.D., M.Sc., the EPC project director. The EPC is supported by the Agency for Healthcare Research and Quality (contract 290-97-0012).

In conclusion, Dr. Mulrow and her colleagues point out the limitations of this study. In particular, they note that most studies were short-term (less than 8 weeks duration), focused exclusively on relief of depressive symptoms, and were conducted under rigorously controlled conditions necessary to evaluate efficacy. Longer term trials that could provide more informative data on adverse effects and the sustainability of beneficial effects are lacking. They call for effectiveness studies to evaluate the relative benefits of treatments under usual clinical conditions, research to determine whether combinations of antidepressants or antidepressants plus psychosocial treatments are more effective than treatment with an antidepressant alone, more studies on the relative benefits of St. John's wort compared with newer antidepressants, and research on the efficacy of antidepressants in patients with coexisting chronic conditions.

More details are in "A systematic review of newer pharmacotherapies for depression in adults: Evidence report summary," by John W. Williams Jr., M.D., M.H.S., Dr. Mulrow, Elaine Chiquette, Pharm.D., and others, in the May 2, 2000 Annals of Internal Medicine 132(9), pp. 743-756.

Editor's Note: The journal article summarized here was drawn from the evidence report, Treatment of Depression—Newer Pharmacotherapies (AHRQ Publication No. 99-E014). Copies of the report and a companion summary (AHRQ Publication No. 99-E013) are available from the AHRQ Publications Clearinghouse.

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