title: Rapid and non-rapid cycling bipolar disorder: a meta-analysis of clinical studies.
abstract: 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 non-rapid cycling.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Altrecht Institute for Mental Health Care and University Medical Center Utrecht, Utrecht, The Netherlands. r.kupka@planet.nl
authors.forename: Ralph W
authors.initials: RW
authors.lastname: Kupka
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.forename: Robert M
authors.initials: RM
authors.lastname: Post
authors.forename: Gabriele S
authors.initials: GS
authors.lastname: Leverich
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
mesh_terms: D001714:Bipolar Disorder / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D006801:Humans; D008137:Longitudinal Studies; D011379:Prognosis; D012307:Risk Factors