Commentary:

This Commentary summarizes findings from three other papers in this issue with recommendations for evidence-based treatment with lithium, anticonvulsants, antipsychotics, and antidepressants in bipolar disorder. We will also provide a summary of levels of evidence and examine two important methodological issues in assessing drug-induced mania: reliance on significance testing for assessment of side-effects, and limitations of randomized controlled trials (RCTs) for assessing frequency of side-effects. If a study is not specifically powered and designed to assess a side-effect, then no significance testing should be conducted, and side-effects should simply be reported as effect estimates and confidence intervals. Further, RCTs only establish a categorical response to a research question, i.e. whether or not something happens. The frequency of an event (treatment response, side-effects) is often more accurately assessed with observational studies.