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Objective We aimed to explore whether the prevalence of manic switch was underestimated in randomized controlled trials ( RCTs) compared to observational studies ( OSs). Method Meta-analyses and simple and systematic reviews were identified by two reviewers in a blinded, standardized manner. All relevant references were extracted to include RCTs and OSs that provided data about manic switch prevalence after antidepressant treatment for a major depressive episode. The primary outcome was manic switch prevalence in the different arms of each study. A meta-regression was conducted to quantify the impact of certain variables on manic switch prevalence. Results A total of 57 papers (35 RCTs and 22 OSs) were included in the main analysis. RCTs underestimated the rate of manic switch [0.53 (0.32-0.87)]. Overestimated prevalence was related to imipraminics [1.85 (1.22-2.79)]; to serotonin-norepinephrine reuptake inhibitors [1.74 (1.06-2.86)]; and to other classes of drugs [1.58 (1.08-2.31)], compared to placebo treatment. The prevalence of manic switch was lower among adults than among children [0.2 (0.07-0.59)]; and higher [20.58 (8.41-50.31)] in case of bipolar disorder. Conclusion Our results highlight an underestimation of the rates of manic switch under antidepressants in RCTs compared to the rates observed in observational studies. [ABSTRACT FROM AUTHOR]

Objective To detail the disconnect between the quantified efficacy of the mood stabilizer lamotrigine in its registration controlled trials and its later judged clinical effectiveness and consider some determinants of disconnects between some efficacy trial findings and 'real-world' clinical effectiveness judgments. Method Published articles considering lamotrigine as a treatment for the bipolar I or II disorders were selected for review. While randomized controlled trials were weighted, we also consider open trials and effectiveness observations from clinician researchers and demonstrate that lamotrigine has been quite variably judged over time. Results We suggest that the early trials evaluating lamotrigine for acute bipolar disorder depression focused on a suboptimal clinical target, and in so doing, ensured less lamotrigine efficacy compared with trials of bipolar disorder preventative treatment. Moreover, a number of additional methodological limitations compromised analyses. We also detail variable reporting of actual study results. The initial sharp disconnect (between efficacy and effectiveness judgments) has narrowed as lamotrigine has been evaluated and progressively taken up as a maintenance mood stabilizer. Conclusion The lamotrigine disconnect story provides a number of salutary lessons that are salient to evaluating the effectiveness and ecological niche of any psychotropic medication. The lamotrigine story presented here argues strongly for the wisdom of encouraging an iterative process between efficacy studies and clinical observation. [ABSTRACT FROM AUTHOR]