During the last decade a number of meta-analysis questioned the clinically relevant efficacy of antidepressants. Part of the debate concerned the method used in each of these meta-analysis as well as quality of the data set. The results suggest that antidepressants have a standardized effect size equal to 0.34 which is lower but comparable to the effect of antipsychotics in schizophrenia and acute mania. The raw HDRS difference from placebo varies significantly with the value of 3 included in the confidence interval. No value of initial severity was found after partially controlling for the effect of structural (mathematical) coupling. Although data are not definite, even after controlling for baseline severity, there is strong possibility that venlafaxine is superior to fluoxetine, suggesting a superiority of double-acting agents. The decrease in the difference between agent and placebo in more recent studies in comparison to older ones is attributed to baseline severity alone. The results reported here, suggest that baseline severity cannot be utilized to dictate or not treatment with medication. Suggestions like this, proposed by guidelines or institutions (e.g. the NICE) should be considered mistaken. Meta-analysis on the available treatments for mania and bipolar depression have also been conducted with much debate concering the interpretation of their results and their utility for the everyday clinical practice.