Rapid and Non-Rapid Cycling Bipolar Disorder: A Meta-Analysis of Clinical Studies
J Clin Psychiatry 2003;64:1483-1494
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Background: Rapid cycling, defined as 4 or more
mood episodes per year, is a course specifier of bipolar disorder
associated with relative treatment resistance. Several risk
factors have been suggested to be associated with rapid cycling.
The purpose of this meta-analysis was to compare clinical studies
for the evidence of discriminating factors between rapid and
Data Sources and Selection: We searched MEDLINE
and reference lists of articles and book chapters and selected
all of the clinical studies published from 1974 to 2002 comparing
subjects with rapid and non-rapid cycling bipolar disorder.
Prevalence rates and mean random effect sizes for 18 potential
risk factors that were reported by at least 3 studies were
calculated. In addition, we differentiated between current and
lifetime diagnoses of rapid cycling.
Data Synthesis: Twenty studies were identified.
Rapid cycling was present in 16.3% of 2054 bipolar patients in 8
studies that included patients who were consecutively admitted to
an inpatient or outpatient facility, without a priori selection
of rapid cyclers and without matching the numbers of rapid
cyclers to non-rapid cycling controls. Female gender and bipolar
II subtype both had a small, but statistically significant,
effect (p < .000 for female gender, p < .001 for bipolar II
subtype). The further absence of recurrences with lithium
prophylaxis was reported in 34% of rapid cyclers compared with
47% of non-rapid cyclers, a nearly significant difference, and a
partial response was present in 59% and 65% of patients,
respectively. The effect of hypothyroidism was significant (p
< .01) in studies using current, but not lifetime, definitions
of rapid cycling. In 46% of cases, a rapid cycling course was
preceded by treatment with antidepressants, but systematic data
on their causal role are lacking.
Conclusion: Rapid cycling is slightly more
prevalent in women and in patients with bipolar II subtype. In
contrast to common opinion, lithium prophylaxis has at least
partial efficacy in a considerable number of rapid cyclers,
especially when antidepressants are avoided. Hypothyroidism may
be associated with mood destabilization in vulnerable patients.