Burning issues in the meta-analysis of pharmaceutical trials for depression

Abstract

During the last decade a number of meta-analytic studies have been published and they triggered a debate on the true clinical usefulness of antidepressants. The current article comments on problems within the randomized controlled trials design, the study samples, the psychometric scales, the methods of meta-analysis, the interpretation of the results, and the reporting of conflicts of interest. Although the meta-analyses published so far agree that medication works in severe depression, they question its efficacy in mild cases. However, several methodological issues should be clarified before conclusions are definite. Different methods give different results and similar results seem to entertain a variety of interpretations. In the future it is important to address all of these problems, and to improve methodology on the basis of clinically informed choices. Otherwise, meta-analysis risks alienation from clinical reality and thus risks becoming the 21(st) century psychoanalysis.

The International College of Neuropsychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 1: Background and Methods of the Development of Guidelines

“…Meta-analytic studies often violate this rule and include a diverse group of trials in the analysis (e.g., studies of monotherapy and combination treatment, fixed and flexible dosage studies, etc.) with unknown consequences (Fountoulakis et al, 2014). …”

From Randomized Controlled Trials of Antidepressant Drugs to the Meta-Analytic Synthesis of Evidence: Methodological Aspects Lead to Discrepant Findings

“…It is also interesting that there is a large variability between sites and countries. North America and Western Europe experience great difficulties in the recruitment of patients while on the contrary, eastern European countries and China recruit participants much easier and faster [ 4 ]. The presence of medical comorbidities as well as the history of response to medications in the past do not seem to be consistently reported in most RCTs [ 45 , 46 ].…”

“…Meta-analysis is regarded as the ‘gold standard’ approach for the evaluation and ranking of evidence in healthcare [ 1 , 2 ]. However, important concerns related to the conduct of meta-analyses have emerged in the literature [ 3 , 4 ]. Notwithstanding meta-analysis as a relevant method to synthesize and rank research data [ 5 ], a number of methodological issues and the presence of inherent biases ( e.g ., heterogeneity and discrepant methodologies across included trials) often lead to erroneous meta-analytic results and interpretations [ 4 , 6 , 7 ].…”

Why Systematic Review rather than Narrative Review?

“…The basic problem of non-systematic search of data is that beneath the shining surface, it seems that the authors utilizing it often misunderstand the true value, underpinning meanings and correct nature of the data, or their true limitations and strengths, and they often go too far or short with the interpretation. 6 Indeed, the main conclusion of a narrative review may often be based on evidence, but such reviews themselves are not rigorous evidence since such reviews are too selective and thus little good quality information could be included. 2 In addition, I found one olanzapine trial was OLS but they included the study in the result (this is a mixture of data yielding a huge heterogeneity).…”