title: The long-term course of rapid-cycling bipolar disorder.
abstract: BACKGROUND
  Rapid cycling among patients with bipolar affective disorders is important because of its implications for long-term prognosis and for the use of antidepressants. To our knowledge, no prospective study has, as yet, described the course of this phenomenon beyond 5 years.
  
  
  METHODS
  From 345 patients with bipolar I or bipolar II disorder followed up for a mean (SD) of 13.7 (6.1) years as part of the National Institute of Mental Health Collaborative Depression Study, 89 (25.8%) were identified who, during 1 or more years of follow-up, manifested a pattern that met DSM-IV criteria for rapid cycling. These patients were compared with the remaining bipolar patients by demographics, overall affective morbidity, morbidity during specific treatment conditions, and the likelihood of suicidal behavior. Analyses assessed whether the use of tricyclic antidepressants for depressive symptoms was associated with the persistence of rapid cycling or with tendencies to switch from depressive to manic or hypomanic phases.
  
  
  RESULTS
  The 89 patients who showed a rapid cycling pattern were significantly more likely to have had an illness onset before 17 years of age and were more likely to make serious suicide attempts. In 4 of 5 cases, rapid cycling ended within 2 years of its onset. Resolutions were not associated with decreases in tricyclic antidepressant use. Throughout follow-up, patients prone to rapid cycling experienced more depressive morbidity than other bipolar patients, particularly when lithium carbonate was being used without tricyclic antidepressants. The use of these antidepressants was not more likely in the weeks preceding shifts from depression to mania or hypomania.
  
  
  CONCLUSIONS
  These results indicate that bipolar patients who develop a rapid cycling pattern suffer substantial depressive morbidity and are at high risk for serious suicide attempts. These findings do not implicate tricyclic antidepressants or, by inference, serotonin reuptake inhibitors in the promotion of affective instability.
authors.affiliation: National Institute of Mental Health Collaborative Program on the Psychobiology of Depression-Clinical Studies, National Institutes of Health, Bethesda, MD, USA. william-coryell@uiowa.edu
authors.forename: William
authors.initials: W
authors.lastname: Coryell
authors.forename: David
authors.initials: D
authors.lastname: Solomon
authors.forename: Carolyn
authors.initials: C
authors.lastname: Turvey
authors.forename: Martin
authors.initials: M
authors.lastname: Keller
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Leon
authors.forename: Jean
authors.initials: J
authors.lastname: Endicott
authors.forename: Pamela
authors.initials: P
authors.lastname: Schettler
authors.forename: Lewis
authors.initials: L
authors.lastname: Judd
authors.forename: Timothy
authors.initials: T
authors.lastname: Mueller
mesh_terms: D000328:Adult; D017668:Age of Onset; D000927:Anticonvulsants / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000188:drug therapy / Q000523:psychology*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D013406:Suicide, Attempted / Q000523:psychology / Q000706:statistics & numerical data; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D008094:Lithium