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Inert placebos can have significant antidepressant effects, and so to establish a substance as an " antidepressant " in a clinical trial it is necessary to show superior efficacy to placebo.
A review of both published and unpublished trials submitted to the U. S. Food and Drug Administration ( FDA ) found that the published trials had a 94 % success in treating depression while the unpublished literature had below 50 % success.
Combined, 51 % of all studies showed efficacy.
The difference in effect between active placebos and several anti-depressants appeared small and strongly affected by publication bias.
There is some evidence to suggest that mirtazapine and venlafaxine may have greater efficacy than other antidepressants in the treatment of severe depression.

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