Roest, A.M., de Jonge, P., Williames, G.D., de Vries, Y.A., Shoevers, R.A., & Turner, E.H. (2015). Reporting bias in clinical trials investigating second-generation antidepressants in the treatment of anxiety disorders: A report of 2 meta-analyses. JAMA Psychiatry, doi:10.1001/jamapsychiatry.2015.15.
Previous research has shown that the effects of antidepressant medications for treating depression may be over estimated by as much as 35%. This occurs because of publication bias, which refers to the tendency among researchers and editors to prefer to publish positive findings, and also occurs due to the occasional practice of the pharmaceutical industry to suppress negative findings. In these meta analyses, Roest and colleagues assess publication bias in the research of antidepressant medications to treat anxiety disorders (i.e., generalized anxiety disorder [GAD], panic disorder [PD), social anxiety disorder [SAD], post traumatic stress disorder [PTSD], and obsessive compulsive disorder [OCD]). Anxiety disorders are very common in the population, with an estimated year-prevalence of 12%. Second generation antidepressants (i.e., selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors) are the primary pharmacologic treatment for anxiety disorders. Roest and colleagues were also interested in outcome reporting bias, which refers to mis-reporting non-positive findings as if they were positive findings, and spin which refers to interpreting non-positive results as beneficial findings. Positive findings refer to the pharmacological agent significantly outperforming a placebo, and non-positive findings refer to pharmacological agents not significantly outperforming a placebo. Pharmaceutical companies in the US must register any trial with the Food and Drug Administration (FDA) prior to starting the trial if the company wishes to apply for US marketing approval. And so, all medication trials and their findings, whether positive or non-positive must be listed in the FDA register. Despite being listed with the FDA, not all trials and findings get published in peer reviewed journals. This causes a problem for reviews and meta analyses that tend only to focus on published trials, and prescribing physicians tend only to read published trials and reviews. In their meta analyses Roest and colleagues compared findings from all FDA registered medication trials to those that were published in peer reviewed journal. Fifty seven trials were registered with the FDA but only 48 were published. Regarding publication bias, the proportion of studies with positive findings indicating efficacy of antidepressant medications in FDA trials was 72%, whereas the proportion of studies with positive findings in trials published in a journal was 96%. Overall, trials were 5 times more likely to be published if they were positive than if they were non-positive. Regarding outcome reporting bias, 3 of 16 trials that were non-positive in the FDA review were reported as positive in journal publications. Regarding spin, an additional 3 of the 16 non-positive trials interpreted non-positive results as if they were positive. Effect sizes in the FDA data was g = .33 indicating a small average effect size of the medications for anxiety disorders, but the effect size in published journals was g = .38 indicating a small to moderate effect. This represents a 15% over estimation of the effects of the antidepressant medications for anxiety disorders in the published literature.
The effects of antidepressant medications for anxiety disorders appear to be over estimated by 15% in the published literature. This inflation is not as large as the 35% over estimation in the published literature of the effects of antidepressant medications for depression. By contrast, as I reported in a previous PPRNet Blog, publication bias in psychotherapy trials is small and has little impact on the overall estimate of psychotherapy’s efficacy. Effect sizes for psychological interventions for anxiety disorders are moderate to large, g = .73. Combining medications and psychotherapy only modestly improves efficacy of treatments, and medications may interfere with the efficacy of psychological interventions.