Rapid Cycling in Bipolar Disorder: A Systematic Review

Objective: The long-term course of bipolar disorder is typified by recurring mood episodes of opposite polarity as well as mixed states. Rapid-cycling bipolar disorder refers to the presence of at least 4 mood episodes in the previous 12 months that meet the criteria for manic, hypomanic, or major depressive episode. The purpose of this study was to synthesize data regarding prevalence, clinical correlates, and familial/genetic aspects related to rapid cycling in bipolar disorder.

Data Sources: We searched the MEDLINE database through September 7, 2013 for articles regarding rapid cycling in bipolar disorder. Searches were performed using the keywords rapid cycling or rapid-cycling. The search strategy was augmented through the inspection of reference lists of relevant review articles. Eligible articles included original studies in English on rapid-cycling bipolar patients according to the criteria defined by the Diagnostic and Statistical Manual of Mental Disorders.

Study Selection: This study followed the recommendations of the Preferred Items for Reporting of Systematic Reviews and Meta-Analyses statement. The initial search returned 2,715 articles; 2,594 were excluded for several reasons (not aligned with objectives, pertaining to bipolar disorder but not focusing on rapid cycling, case reports, and case series). The final review included 119 articles.

Data Extraction: Two investigators (K.N.F. and D.D.) independently reviewed articles for eligibility. Final decisions regarding eligibility were made by consensus following the full-text review.

Results: The literature suggests that rapid cycling affects a significant proportion of bipolar patients and is related to a longer course of illness, an earlier age at onset, and more illegal drug and alcohol abuse and increased suicidality. Year prevalence of rapid cycling among all bipolar patients ranges between 5%-33.3%, while lifetime prevalence ranges between 25.8%-43%. The etiology remains unclear, although a causal or triggering role for the use of antidepressants and hypothyroidism is implicated. Rapid cycling seems to represent a transitory phenomenon rather than a stable pattern that characterizes the individual patient and probably is related to a worse outcome.

Conclusions: Rapid cycling is a frequent, although underrecognized, condition in bipolar disorder, and it constitutes a worsening of the primary disorder. There is no good evidence that rapid cycling represents a discrete subtype. Early recognition of this pattern can lead to better treatment strategy and improvement of the long-term course. Conceptualizing rapid cycling according to Research Domain Criteria will be an important advance.