Antidepressant medications probably provide little or no benefit to people with mild or moderate depression, a new study has found. Rather, the mere act of seeing a doctor, discussing symptoms and learning about depression probably triggers the improvements many patients experience while on medication.

Only people with very severe depression receive additional benefits from drugs, said the senior author of the study, Robert J. DeRubeis, a University of Pennsylvania psychology professor. The research was released online Tuesday and will be published today in the Journal of the American Medical Assn.

Hundreds of studies have attested to the benefits of antidepressants over placebos, DeRubeis said. But many studies involve only participants with severe depression. Confusion arises, he said, “because there is a tendency to generalize the findings to mean that all depressed people benefit from medications.”

The current analysis attempted to quantify how much of antidepressants’ benefit is attributable to chemical effects on the brain and how much can be explained by other factors, such as visiting a doctor, taking action to feel better or merely the passage of time.


Researchers reviewed six randomized, placebo-controlled studies with a total of 718 patients who took either an antidepressant or placebo. The patients were adults with levels of depression ranging from mild to very severe based on the Hamilton Depression Rating Scale, a questionnaire widely used in depression research. The studies did not exclude patients who were likely to have a strong response to a placebo. Researchers then compared the patients’ depression scores at the beginning of treatment with those after at least six weeks of treatment.

The study found that the magnitude of the drugs’ benefit increased with the baseline level of depression. The effect of treatment was similar in people with mild, moderate and severe symptoms, regardless of whether they took an antidepressant or placebo. Only the people who rated very severe on the depression scale at the start of the study showed measurable improvements on antidepressants.

“There is no doubt that there are tremendous benefits from antidepressants, as our study showed,” DeRubeis said. “But this study helps us resolve, to some degree, the question of how much benefit people can expect from the medicines themselves when symptoms are not severe.”

Other research has also found that antidepressants are most effective for severe symptoms, said Dr. Philip Wang, deputy director of the National Institute of Mental Health. Though it could be that antidepressants don’t work well for mild to moderate depression, it’s also possible that people enrolled in antidepressant studies have robust placebo responses that mask some of the impact of the medication.


A severely depressed person who would probably benefit from antidepressants might have symptoms such as frequent weeping, feelings of guilt and sadness, thoughts that life is not worth living, problems sleeping, fatigue and withdrawal from normal activities, DeRubeis said.

Better antidepressants are needed for people with mild to moderate depression, Wang said, as is research on how to diagnose depression with tools, such as biomarkers, that could help personalize treatment.

Of the six studies in the current analysis, three involved selective serotonin reuptake inhibitors, or SSRIs, the most commonly used antidepressants, and three involved an older class of medications called tricyclics. Both classes are thought to be equally effective, although SSRIs are associated with fewer side effects.

One exception to the study findings, DeRubeis said, was people with dysthymia, or chronic, low-level depression. The analysis assessed severity of symptoms, not chronicity, he said. Other studies have established that people with chronic depression, no matter how severe, tend to respond well to antidepressants while other treatment may be ineffective.


shari.roan@latimes.com