Review articleLong-term treatment response to continuous cycling course in bipolar disorders: A meta-analysis.
Introduction
In a pioneering work, Koukopoulos et al. (1980) identified four patterns of course in bipolar disorders (BD): 1) manic–depression-free interval (MDI; in which the cycle starts with (hypo)mania, followed by depression and then by a free interval); 2) depression–mania-free interval (DMI; in which the cycle starts with depression, followed by (hypo)mania, and then by a free interval); 3) continuous cycling course (CCC), with depressive and (hypo)manic episodes alternating without a real free interval (i.e., an interval of at least one month, without significant mood symptoms); and 4) irregular course of cycle sequence (IRR) in which the sequence of depression–(hypo)mania–free interval is irregular). The authors distinguished two subtypes of CCC: long-cycle (CC–LC), with < 4 episodes per year, and short-cycle (CC–SC), with > 4 episodes per year.
As reported in our previous review paper (Tundo and Cavalieri, 2018) research studies showed that an average of 27% of bipolar patients (range 6–39%) experience CCC and that these patients remarkably differ from those with a free interval because they have a later onset, different polarity at onset (more depressive than mixed), different polarity of subsequent episodes (more depressive and (hypo)manic than mixed), higher switch rates, and poorer short-term response rate to antidepressant treatment during major depressive episodes. Notably, Maj et al. (1999), observed that CC–SC does not correspond entirely to rapid cycling BD according to DSM–IV criteria but identifies the most severe subtype of rapid-cycling with a free interval of less than one month, a stable pattern over time, a poor prognosis, and poor treatment response. Furthermore, Kleindienst et al. (2005) investigating 42 potential clinical predictors to lithium prophylaxis response in BD, found that CCC is significantly related to poor response to lithium. To our knowledge, no studies subsequently reviewed the available evidence on this topic including long-term response not only to lithium but also to complex polypharmacy. Indeed, patterns of course in BD have been neglected in psychiatry until recently. However, there is now an increased impetus to characterize major psychiatric disorders, including BD (McKnight et al., 2017, Frías et al., 2017, Sani et al., 2017) and schizophrenia (Chang et al., 2018, Millan et al., 2016) by the patterns of course. The characterization of clinical patterns can potentially improve our understanding of BD, and lead to more effective treatment strategies. Our hypothesis was that CCC patients had more severe illness and a poorer response to long-term treatment compared with NCCC patients.
Our systematic review and meta-analysis aims to assess the long-term treatment response in patients with BD and CCC pattern versus patients with BD and NCCC.
Section snippets
Literature search
We searched PubMed/MEDLINE, Cochrane CENTRAL and Embase from the date of database inception to March 18th 2018, to identify relevant, peer-reviewed articles on CCC in adult patients with BD. The search syntax was based on combinations of the terms: mood disorders, depression, affective symptoms, affective disorder*, mood disorder*, bipolar, mania, manic, hypomani*, rapid cycling, continuous cycl*,continuous circular.
We searched for ongoing and unpublished studies via Internet searches on
Results
The literature search generated 1899 articles. We found five duplicates that were excluded. We therefore reviewed 1894 titles and abstracts, including 61 possibly relevant records, which were then evaluated in full-text. Of these, 17 studies were excluded because they were reviews; 15 studies did not differentiate patients on the different pattern of course;10 studies did not focus on BD; 13 studies did not report outcome on treatment response. Finally, we identified six observational studies
Discussion
Our findings show that patients with BD and CCC pattern are significantly poorer responder to long-term treatment compared with patients with BD and NCCC pattern. This result is consistent with those of a previous meta-analysis on lithium monotherapy long-term response (Kleindienst et al., 2005) and a previous naturalistic study on polypharmacy long-term response (Tundo et al., 2013). The reason for the different long-term treatment response in patients with CCC and NCCC pattern of course is at
Conflict of interest
The authors declare no conflict of interest.
Authors contributions
Antonio Tundo designed the research, and reviewed the manuscript.
Paola Cavalieri managed the literature search and wrote the first draft of the manuscript.
Davide Gori and Franco De Crescenzo conducted the meta-analysis.
All authors contributed to and approved the final manuscript.
Funding
This study was funded by the Fondazione dell'Istituto di Psicopatologia Onlus, (Grant no. 01/2016) Rome, Italy.
Ethical standards
The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.
Acknowledgment
The authors thank Roberta Necci for her technical help and support in translation.
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