Anti-Inflammatory Treatments for Depression: Perspectives on How to Read a Meta-Analysis Critically

Inflammatory mechanisms have been implicated in many psychiatric disorders, including depression, and anti-inflammatory agents have been suggested as potential treatments. In this context, a systematic review and meta-analysis of nonsteroidal anti-inflammatory drugs, cytokine inhibitors, glucocorticoids, statins, minocycline, and pioglitazone, all of which are considered to have anti-inflammatory properties, examined the antidepressant benefits of these agents in 36 randomized controlled trials conducted in patients with major depressive disorder (MDD) and patients with medical diseases and associated depressive symptoms. The meta-analysis found that, overall, relative to placebo, these drugs had superior antidepressant effect in patients with MDD as well as in those with medical disease. With the exception of pioglitazone, every drug/category also outperformed placebo. However, the findings of this extensive meta-analysis do not guide theory; because the different anti-inflammatory agents studied have multiple pharmacodynamic actions, there is no assurance that their anti-inflammatory mechanism was responsible for the reported antidepressant benefits. The findings do not guide clinical practice, either, because of substantial clinical and statistical heterogeneity; no specific drug, dose, duration of treatment, and disorder were identified for application of the findings. Finally, the meta-analysis contained obvious and non-obvious errors, including the combination of endpoint and improvement scores in the same summary estimate (standardized mean deviation) and the use of percentage scores rather than absolute scores in the computations. These issues are explained so that readers can more easily consider or detect the limitations of meta-analyses that are published.