Fountoulakis KN, Kontis D, Gonda X, Yatham LN. A systematic review of the evidence on the treatment of rapid cycling bipolar disorder. Bipolar Disord 2013: 15: 115-137. (c) 2013 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objective: Rapid cycling is associated with longer illness duration and greater illness severity in bipolar disorder. The aim of the present study was to review the existing published randomized trials investigating the effect of treatment on patients with rapid cycling bipolar disorder. Methods: A MEDLINE search was conducted using combinations of the following key words: bipolar and rapid or rapid-cycling or rapid cycling and randomized. The search was conducted through July 16, 2011, and no conference proceedings were included. Results: The search returned 206 papers and ultimately 25 papers were selected for review. Only six randomized, controlled trials specifically designed to study a rapid cycling population were found. Most data were derived from post hoc analyses of trials that had included rapid cyclers. The literature suggested that: (i) rapid cycling patients perform worse in the follow-up period; (ii) lithium and anticonvulsants have comparable efficacies; (iii) there is inconclusive evidence on the comparative acute or prophylactic efficacy of the combination of anticonvulsants versus anticonvulsant monotherapy; (iv) aripiprazole, olanzapine, and quetiapine are effective against acute bipolar episodes; (v) olanzapine and quetiapine appear to be equally effective to anticonvulsants during acute treatment; (vi) aripiprazole and olanzapine appear promising for the maintenance of response of rapid cyclers; and (vii) there might be an association between antidepressant use and the presence of rapid cycling. Conclusion: The literature examining the pharmacological treatment of rapid cycling is still sparse and therefore there is no clear consensus with respect to its optimal pharmacological management. Clinical trials specifically studying rapid cycling are needed in order to unravel the appropriate management of rapid cycling bipolar disorder.