Beyond evidence-based treatment of bipolar disorder: Rational pragmatic approaches to management.

The evidence for efficacy of many currently available treatments for bipolar disorder is based on studies of nonrefractory patients with bipolar disorder. Therefore, not surprisingly, most treatment recommendations and guidelines for the treatment of bipolar disorder and its many comorbidities depend heavily on data from placebo controlled randomized clinical trials (RCTs), but these RCTs provide little direction for the clinician as to what next steps might be optimal in non- or partial-responders and in those with ongoing medical and psychiatric comorbidities. Given this and the paucity of RCTs at later treatment junctures, we thought it appropriate to begin a discussion of the quality of the data that some experts in the field might consider using in choosing and sequencing drugs and their combination. We acknowledge that many other clinical investigators may prefer very different sequences, but thought the suggestions offered here might be useful to some clinicians in the field, might start discussions of other options in the literature, and, at the same time, provide a preliminary outline for a new round of much-needed clinical trials to better inform clinical practice. Given the very wide range of the quality of the data and clinical principles on which the current suggestions are based, only minimal references are included and a comprehensive review of the literature supporting each option would be outside the scope of this manuscript.