Second, in order to demonstrate statistically in a controlled study that antidepressants produce a preventive effect in respect of the profound but nonetheless relatively rare event of a completed suicide, we would need a sample size of 20.000 people randomly treated with either antidepressants or placebo. This may be difficult to achieve in practice given 
that suicidal risk tends to be an exclusion criterion in antidepressant trials, naturalistic or experimental. Third, it would be unacceptable for ethical reasons to conduct a randomized controlled trial with suicide as an outcome variable. This rebuffs most criticisms and scepticism on observable antidepressant effects on suicide decrease, usually stating that suicide had already started to decrease before antidepressant utilization exploded, in the nineties, therefore denying earlier generation antidepressant effects. This study has also many advantages over single national studies, though it does not substitute for them: it controls for the variability of factors that affect suicide rates at the country level and it has more explanatory power on the role of antidepressants on suicide rates because of the number of observations Ginsenoside-F2 involved. We also believe it purports more power than reviews and metaanalysis produced so far because of its consistency: close geographic and socio-political context in the last 10 years, use of available annual data series, inclusion of all families of antidepressants and use of DDD/1000/day. In fact, single studies and reviews have used several definitions of antidepressant utilization, including costs, number of packages or pills sold, number of prescriptions issued, defined daily dosage and defined daily doses per thousand individuals per day. These discrepancies hinder comparability and introduce probable sources of bias because drug costs, pills dosages, quantities of pills per package and prescriptions, might oscillate longitudinally because of external, regulatory and commercial reasons. Using DDD/1000/day represents a stable variable for the estimation of the exposure to drugs and the proportion of the population that may receive treatment with a particular drug on a daily basis. Another source of bias in some previous studies has been associated with a major focus on SSRIs, and not on the analysis of the use of the whole class of antidepressants, including SNRIs, atypicals and tryciclics. Patterns in the use of these drugs might vary considerably across countries. Moreover, these studies present substantial differences in the periods of time that are analysed, both for antidepressant use and recorded suicides, from as low as 2 years to as high as 30 years for antidepressant use utilization series, and a similar but slightly better pattern for suicide time series. It is likely that these variations will have had an impact on results, as well as making meaningful comparison difficult. The extent to which data series are available across Atractylenolide-III countries for the same time periods can influence correlation results strikingly. This is quite important to assess previous and future studies: results are far more reliable when longer yearly time series are present. Our study presents an average of 15 years of both annual suicide and antidepressant utilization data, the largest figure to our knowledge, albeit hampered by inconsistent time series data for antidepressant utilization across countries. There is also considerable variability of statistical procedures within studies published so far, which further complicates comparing results. Most studies present differing correlations, linear regressions, Poisson regressions and time series; we avoid this problem in our multi-country analysis.