Rapid Cycling: Still a “Foggy” Situation

Although cycling acceleration was portrayed long ago, when Bleuler described a 50-hour cycle in a patient suffering from a mood disorder, the limited existing data do not allow clear conclusions regarding the clinical phenomenology, prevalence, and clinical correlates associated with rapid cycling.¹

Additionally, misconceptions exist regarding overlap between this clinical variable and other clinical phenotypes. For example, patients with rapid cycling bipolar disorder are often misdiagnosed as suffering from a mixed episode. The only clinical situation, however, in which a manic or a hypomanic episode coexists in the same period of time as a full-blown major depressive one (as required by the modern classification systems) is within the nosological entity recognized as ultra-rapid cycling.²

Some fundamental questions about rapid cycling remain more or less unanswered. Is it a frequent clinical situation? How is it triggered? Is there a recognized relationship with environmental factors? Is there a specific biological substrate? Is it a real subtype with temporal stability or is it a course specifier?

To answer some of these questions, my colleagues and I performed a systematic review³ of the available data regarding rapid cycling, which was recently published in The Journal of Clinical Psychiatry.

We found some interesting answers. First of all, it seems that rapid cycling is a rather frequent clinical condition. Although the prevalence rates vary widely, we calculated that the mean weighted annual prevalence rate is 18.10%, while the lifetime prevalence rate is estimated to be 31.48%.³ Moreover, prevalence seems dissimilar among females and males, and a previous meta-analysis by Kupka and colleagues⁴ reported a close association between female gender and rapid cycling. Regarding age at onset, it seems that bipolar illness begins earlier among patients with rapid cycling (before 17 years) than among those without.

Does rapid cycling have a specific biological substrate? Do environmental triggers exist? A relationship between rapid cycling and hypothyroidism has been described (but not unanimously accepted) as a part of a more complex inter-correlation that also is associated with female gender and lithium treatment.⁵ Furthermore, the etiological relationship between the use of antidepressants and rapid cycling is less clear than once was thought, as it seems that only a fraction of patients will develop this course after the use of antidepressants.³ Beyond triggering factors, the findings from the field of genetics were not convincing. There is not an increased familial load for rapid cycling bipolar disorder.⁴ Furthermore, despite the existence of genetic studies, their limited number and the lack of replication is still a problem. Overall, the existing data are insufficient and cannot support the existence of a recognizable biological substrate. A hypothesis that deserves further exploration is that possibly temperament is the determining endophenotype, while rapid cycling serves as an intermediate phenotype.³

Finally, although rapid cycling seems like a worsening in the course of bipolar disorder, it does not happen in a predictable manner. Rapid cycling seems to represent a transitory phenomenon rather than a stable phase or feature of the disorder in the majority of cases.³

Financial disclosure:Dr Dimellis has received honoraria from Janssen-Cilag, Eli Lilly, Pfizer, Servier, and AstraZeneca and is a member of the speakers/advisory boards for Janssen-Cilag, Eli Lilly, Pfizer, Servier, AstraZeneca, and Sanofi.

References

1. Fountoulakis KN, Akiskal HS. Focus on bipolar illness. CNS Spectr. 2008;13(9):762. PubMed

2. Fountoulakis KN, Kontis D, Gonda X, et al. Treatment of mixed bipolar states. Int J Neuropsychopharmacol. 2012;15(7):1015–1026. PubMed

3. Carvalho AF, Dimellis D, Gonda X, et al. Rapid cycling in bipolar disorder: a systematic review. J Clin Psychiatry. 2014;75(6):e578–586. Abstract

4. Kupka RW, Luckenbaugh DA, Post RM, et al. Rapid and non-rapid cycling bipolar disorder: a meta-analysis of clinical studies. J Clin Psychiatry. 2003;64(12):1483–1494. Abstract

5. Bauer MS, Whybrow PC, Winokur A. Rapid cycling bipolar affective disorder: I. Association with grade I hypothyroidism. Arch Gen Psychiatry. 1990;47(5):427–432. PubMed