No role for initial severity on the efficacy of antidepressants: results of a multi-meta-analysis

Introduction: During the last decade, a number of meta-analyses
questioned the clinically relevant efficacy of antidepressants.
Part of the debate concerned the method used in each of these
meta-analyses as well as the quality of the data set. Materials and
methods: The Kirsch data set was analysed with a number of
different methods, and eight key questions were tackled. We fit
random effects models in both Bayesian and frequentist statistical
frameworks using raw mean difference and standardised mean
difference scales. We also compare between-study heterogeneity
estimates and produce treatment rank probabilities for all
antidepressants. The role of the initial severity is further
examined using meta-regression methods. Results: The results
suggest that antidepressants have a standardised 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 is 2.82 with the value of 3 included in the
confidence interval (2.21-3.44). No role 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 a strong possibility
that venlafaxine is superior to fluoxetine, with the other two
agents positioned in the middle. The decrease in the difference
between the agent and placebo in more recent studies in comparison
to older ones is attributed to baseline severity alone. Discussion:
The results reported here conclude the debate on the efficacy of
antidepressants and suggest that antidepressants are clearly
superior to placebo. They also suggest that baseline severity
cannot be utilized to dictate whether the treatment should include
medication or not. Suggestions like this, proposed by guidelines or
institutions (e.g. the NICE), should be considered mistaken.