Ceiling effects in the "Effectiveness of adjunctive antidepressant treatment for bipolar depression" study: was the sky the limit?

Abstract

Comments on the articles by G. S. Sachs et al. (see record [rid]2007-12420-003[/rid]), (see record [rid]2007-12420-004[/rid]) and (see record [rid]2007-12420-005[/rid]). The widely discussed study by Sachs et al., namely the Effectiveness of adjunctive antidepressant treatment for bipolar depression is based on a pragmatic trial that randomly assigned bipolar depression patients to receive mood stabilizer plus placebo or mood stabilizer plus antidepressant. It achieved similar results in terms of durable recovery and other secondary outcomes. Considering that the aforementioned study employed a new methodological approach, I believe that it would be worthwhile exploring its advantages and disadvantages so as to be better positioned to interpret current studies, as well as to design new ones. Based on the aspects listed below, I would like to discuss whether or not the study contains a 'ceiling effect' i.e., a false negative finding resulting from performance and selection biases. In the study by Sachs et al., 60% of the patients presented more than 10 previous manic and depressive episodes, thus suggesting that this group may constitute a refractory sample. The primary outcome of the Sachs et al. study was 'durable recovery', defined as eight consecutive weeks of euthymia, with no more than two manic or depression symptoms. In the Sachs et al. study, patients were allowed to increase the dose of the mood stabilizer and enhance the use of pharmacotherapy, psychotherapy, etc. Such factors could have increased the trial 'noise' by increasing non-specific effects at the expense of decreasing the 'signal' of the experimental treatment. Sachs et al. compared mood stabilizer + placebo against mood stabilizer + antidepressant drug. In such type of design, ceiling effects are important since the effect of the combined intervention is weaker compared to the effect of each intervention tested separately. To assess an antidepressant's efficacy, which was probably lower in the Sachs et al. study, the study's design should have included a pure placebo arm. In conclusion, given that the number of pragmatic trials in Psychiatry has increased over time, we are now allowed to test the effectiveness of interventions in the 'real world'. As exemplified by the Sachs et al. study, such trials, however, have certain design characteristics that can lead to ceiling effects. Therefore, when translating results into clinical practice, clinicians should be aware of the possible caveats to be found in pragmatic studies. (PsycINFO Database Record (c) 2016 APA, all rights reserved)