title: Comparison of rapid-cycling and non-rapid-cycling bipolar I manic patients during treatment with olanzapine: analysis of pooled data.
abstract: BACKGROUND
  Rapid-cycling (RC) bipolar disorder patients experience high levels of morbidity, typically respond unsatisfactorily to available treatments, and, so, require additional studies of novel treatments. We report on the first controlled study comparing acute and continuous clinical outcomes in RC and non-RC manic patients treated with olanzapine.
  
  
  METHODS
  We analyzed data pooled from 2 placebo-controlled, double-blind, 3- to 4-week trials of olanzapine in mania (N = 254), 1 with an open-label extension up to 1 year (N = 113) and controlled supplementation with lithium or fluoxetine as needed, to compare demographic, clinical, and outcome measures between RC and non-RC subgroups of 254 DSM-IV bipolar I manic subjects.
  
  
  RESULTS
  RC (N = 90, 35%) versus non-RC subjects (N = 164, 65%) were younger at intake (p = .02), less often psychotic (p < .0001), and more likely to have familial bipolar disorder (p < .0001), abused substances (p = .01), more previous hospitalizations (p = .004), and many more illness episodes (p < .001). In initial blinded trial outcomes, relative responses (> or = 50% improvement of mania) to olanzapine/placebo were similar in RC and non-RC subjects, though early responses to olanzapine favored RC over non-RC subjects (p = .003), and long-term outcomes favored non-RC subjects (p = .05). Fewer RC subjects achieved strictly defined initial symptomatic remission (p = .014) within a year; RC subjects were more likely to experience recurrences (p = .002), especially of depressive illness (< .001), and had more rehospitalizations (p = .01) and suicide attempts (p = .03).
  
  
  CONCLUSIONS
  RC bipolar I patients showed major initial differences and more rapid initial clinical changes, especially toward depression, with less favorable long-term outcomes than non-RC cases during treatment with olanzapine. Inclusion of RC bipolar disorder patients can complicate therapeutic trials, but these patients require further study for differential responsiveness to innovative treatments with methods of assessing clinical response that take their mood instability into account.
authors.affiliation: Bipolar Disorders Program, Department of Psychiatry, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain. evieta@clinic.ub.es
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
authors.forename: John
authors.initials: J
authors.lastname: Hennen
authors.forename: Francesc
authors.initials: F
authors.lastname: Colom
authors.forename: Anabel
authors.initials: A
authors.lastname: Martínez-Arán
authors.forename: Jose
authors.initials: J
authors.lastname: Sánchez-Moreno
authors.forename: Lakshmi N
authors.initials: LN
authors.lastname: Yatham
authors.forename: Mauricio
authors.initials: M
authors.lastname: Tohen
authors.forename: Ross J
authors.initials: RJ
authors.lastname: Baldessarini
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology*; D004354:Drug Screening Assays, Antitumor; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D015201:Meta-Analysis as Topic; D000077152:Olanzapine; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D005473:Fluoxetine; D001569:Benzodiazepines; D008094:Lithium; D000077152:Olanzapine