title: A 20-month, double-blind, maintenance trial of lithium versus divalproex in rapid-cycling bipolar disorder.
abstract: OBJECTIVE
  The authors tested the hypothesis that divalproex would be more effective than lithium in the long-term management of patients with recently stabilized rapid-cycling bipolar disorder.
  
  
  METHODS
  A 20-month, double-blind, parallel-group comparison was carried out in recently hypomanic/manic patients who had experienced a persistent bimodal response to combined treatment with lithium and divalproex. Sixty patients were randomly assigned to lithium or divalproex monotherapy in a balanced design after stratification for illness type (bipolar I versus bipolar II disorder).
  
  
  RESULTS
  Of the 254 patients enrolled in the open-label acute stabilization phase, 76% discontinued the study prematurely (poor adherence: 28%; nonresponse: 26% [of whom 74% remained depressed and 26% remained in a hypomanic/manic/mixed episode], intolerable side effects: 19%). Of the 60 patients (24%) randomly assigned to double-blind maintenance monotherapy, 53% relapsed (59% into depression and 41% into a hypomanic/manic/mixed episode), 22% completed the study, 10% had intolerable side effects, and 10% were poorly adherent. The rates of relapse into any mood episode for those given lithium versus divalproex were 56% and 50%, respectively; the rates were 34% and 29% for a depressive relapse and 19% and 22% for a hypomania/mania relapse. There were no significant differences in time to relapse. The proportion discontinuing prematurely because of side effects was 16% for lithium and 4% for divalproex.
  
  
  CONCLUSIONS
  The hypothesis that divalproex is more effective than lithium in the long-term management of rapid-cycling bipolar disorder is not supported by these data. Preliminary data suggest highly recurrent refractory depression may be the hallmark of rapid-cycling bipolar disorder.
authors.affiliation: Case Western Reserve University, University Hospitals of Cleveland, Cleveland, OH 44106, USA. joseph.calabrese@uhhs.com
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
authors.forename: Melvin D
authors.initials: MD
authors.lastname: Shelton
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rapport
authors.forename: Eric A
authors.initials: EA
authors.lastname: Youngstrom
authors.forename: Kelly
authors.initials: K
authors.lastname: Jackson
authors.forename: Sarah
authors.initials: S
authors.lastname: Bilali
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ganocy
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008094:Lithium / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D010352:Patient Dropouts; D011569:Psychiatric Status Rating Scales; D055502:Secondary Prevention; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; D008094:Lithium