The Use of Statins for Antipsychotic Augmentation in Schizophrenia: Examination of Meta-Analyses With Flawed Methods and Conclusions.

A very large number of psychopharmacologic agents have been trialed as antipsychotic augmentation strategies for the improvement of positive, negative, mood, cognitive, and other symptoms of schizophrenia; statins are one among these. Two very recent meta-analyses examined data on statin augmentation from 5 to 6 randomized controlled trials (RCTs) in the field. One meta-analysis found that statins were superior to placebo for the improvement of total scale and general psychopathology subscale scores on the Positive and Negative Syndrome Scale; statins were no better than placebo for positive and negative subscale outcomes. The other meta-analysis, in contrast, found that statins were superior to placebo for the improvement of positive and negative subscale scores but were no better than placebo for total scale and general psychopathology subscale outcomes. Both meta-analyses were associated with serious flaws such as the combination of studies conducted in contrasting stages of illness, the combination of change and endpoint scores in the same analysis, and the use of numbers that were prima facie incorrect. The first take-home message is that clinicians who read meta-analyses for guidance on how to better treat patients and researchers who read meta-analyses with a view to citing these in their papers both need to exercise due diligence to determine whether what they are reading is valid or flawed. Because this could be a difficult task, journal editors and reviewers need to take more care during manuscript screening and processing than they appear to be doing at present. The second take-home message is that the consideration of statin augmentation is based on very few RCTs and the differences between trial drug and placebo in these RCTs are mostly so small as to be clinically not worth considering.