Continuous circular cycling as a predictor of treatment response in bipolar disorders: a comprehensive review of the current literature

Evidence from the literature suggests that, on average, 27% of patients with a bipolar disorder (BD) experience a continuous cycling course (CCC) and that this subgroup differs significantly from patients with a noncontinuous cycling course (N-CCC) with respect to sociodemographic characteristics and clinical presentation. The aim of the present paper is to review the studies that evaluated short- and long-term treatment responses in BD patients with CCC. The retrieved studies indicate that CCC is a significant predictor of poor response to long-term treatment with lithium (the odds of a response in the CCC group were 57% less than in the N-CCC group; p<0.01), as well as to polytherapies including lithium and/or an antiepileptic augmented, when necessary, with an antipsychotic and/or antidepressant. The percentage of patients without new episodes during follow-up was significantly lower in the CCC group compared with the N-CCC group (15.4 vs. 37.6% , p<0.01). Compared with patients in the N-CCC group, members of the CCC group had a poorer response and lower remission rates after 12-week antidepressant treatments for a major depressive episode (82.3 vs. 50%, p =0.002; 69.6 vs. 40.9%, p=0.013). These findings, underlining that CCC is a predictor of poor response to short- and long-term treatment in BD, should be interpreted considering the limitations of the reviewed studies (the small sample sizes, the small number of trials and their observational nature, the lack of randomization or placebo controls, and the unblinded nature of the outcomes). Clinical trials and observational studies with larger samples are warranted to confirm the conclusions of our review.