How Efficacious Are Antipsychotic Drugs for Schizophrenia- An Interpretation Based on 13 Effect Size Indices

Background: The magnitude of the superiority of antipsychotics over placebo is debated. One reason is that the effect-size index which is usually used in meta-analyses is in standard deviation units. Many other indices, some of which are more intuitive, exist. Methods: We explain the formulae, advantages, and limitations of 13 effect-size indices: Mean Difference (MD), Standardized-Mean-Difference (SMD), Correlation Coefficient, Ratio-of-Means (RoM, endpoint and change data), Improvement Fraction (IF), Drug-Response Fraction (DRF), Minimally-Clinically-Important-Difference-Units (MCIDU), Number-Needed-to-Treat-derived from SMD (NNT), Odds Ratio (OR), Relative Risk (RR), and Risk Difference (RD) derived from SMD, Drug-response and Placebo-response in percent. We applied these indices to meta-analyses comparing antipsychotic drugs with placebo for acute schizophrenia. Results: The difference of all antipsychotics pooled vs placebo (105 trials with 22741 participants) was: MD 9.4 (95% CI 8.4,10.2) PANSS points, SMD 0.47 (0.42,0.51), Correlation coefficient 0.23 (0.21,0.25), RoM endpoint 0.83 (0.81,0.85), RoM change 1.94 (1.84,2.02), IF (%) 49 (46,51), DRF (%) 94 (84,102), MCIDU 0.63 (0.56,0.68), NNT 5 (5,6), OR 2.34 (2.14, 2.52), RR 1.67 (1.59,1.73), RD 20% (18-22), and 50% (48, 52) improved on drug compared to 30% on placebo. Results of individual drugs compared to placebo are presented, as well. Conclusions: Taken together these indices show a substantial, but not a large superiority of antipsychotics compared to placebo. The general chronicity of the patients in the trials must be considered. Future meta-analyses should report other effect size indices in addition to the Standardized-Mean-Difference, in particular percentage responders in the drug and placebo groups. They can be easily derived and would enhance the interpretation of research findings.