Comparing the Evidential Strength for Psychotropic Drugs: A Bayesian Meta-Analysis

Abstract

Objective: Approval and prescription of drugs should be informed by the strength of evidence for efficacy. While there is no formal policy towards different standards for drug approval, the typical strength of evidence might differ for different psychotropic drug groups. Using a Bayesian framework, we examine (1) whether psychotropic drugs are supported by substantial evidence (at the time of Food and Drug Administration [FDA] approval), and (2) whether there are systematic differences across drug groups. Methods: Data from short-term, placebo-controlled phase II/III clinical trials for 15 antipsychotics, 16 antidepressants for depression, nine antidepressants for anxiety, and 20 drugs for ADHD were extracted from FDA reviews evaluating efficacy prior to marketing approval. Bayesian model-averaged meta-analysis was performed and strength of evidence was quantified with the Bayes factor (BFBMA). Results: We observed substantial variation in strength of evidence and trialling between approved psychotropic drugs: Median evidential strength was extremely strong for ADHD medication (BFBMA = 1820.4), but considerably lower and more frequently classified as weak or moderate for antidepressants for both depression (BFBMA = 94.2) and anxiety (BFBMA = 49.8). Differences might be accounted for by varying median effect sizes (schizophrenia: ESBMA = 0.45, depression: ESBMA = 0.30, anxiety: ESBMA = 0.37, ADHD: ESBMA = 0.72), sample sizes (schizophrenia: N = 324, depression: N = 218, anxiety: N = 254, ADHD: N = 189.5), and numbers of trials (schizophrenia: Nr = 3, depression: Nr = 5.5, anxiety: Nr = 3, ADHD: Nr = 2). Limitations: The analysis only included pre-marketing studies. Conclusion: Evidential strength varied across drug groups: Although most psychotropic drugs were supported by strong evidence at the time of approval, some drugs only had moderate or even ambiguous evidence. These results show the need for more systematic quantification and classification of statistical evidence for psychotropic drugs, and for transparent and clear communication of evidential strength toward clinical decision makers.