title: A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder.
abstract: BACKGROUND
  Two clinical trials, prospectively designed for combined analysis, compared placebo, lithium, and lamotrigine for treatment of bipolar I disorder in recently depressed or manic patients.
  
  
  METHODS
  1315 bipolar I patients (DSM-IV) enrolled in the initial open-label phase, and 638 were stabilized and randomly assigned to 18 months of double-blind monotherapy with lamotrigine (N = 280; 50-400 mg/day fixed dose or 100-400 mg/day flexible dose), lithium (N = 167; serum level of 0.8-1.1 mEq/L), or placebo (N = 191). The primary endpoint was time from randomization to intervention for a mood episode. Data were gathered from August 1997 to August 2001.
  
  
  RESULTS
  Lamotrigine and lithium were superior to placebo for time to intervention for any mood episode (median survival: placebo, 86 days [95% CI = 58 to 121]; lithium, 184 days [95% CI = 119 to not calculable]; lamotrigine, 197 days [95% CI = 144 to 388]). Lamotrigine was superior to placebo for time to intervention for depression (median survival: placebo, 270 days [95% CI = 138 to not calculable]; lithium, median not calculable; lamotrigine, median not calculable). Lithium and lamotrigine were superior to placebo for time to intervention for mania (median survival not calculable for any group). Results of additional analyses adjusted for index mood were similar; however, only lithium was superior to placebo for intervention for mania. There was no evidence that either active treatment caused affective switch. Adverse event analysis indicated more diarrhea (19% vs. 7%, p <.05) and tremor (15% vs. 4%, p <.05) in lithium-treated patients compared with lamotrigine-treated patients.
  
  
  CONCLUSIONS
  Lamotrigine and lithium stabilized mood by delaying the time to treatment for a mood episode. Lamotrigine was effective against depression and mania, with more robust activity against depression. Lithium was effective against mania.
authors.affiliation: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, England, UK. Guy.Goodwin@psych.ox.ac.uk
authors.forename: Guy M
authors.initials: GM
authors.lastname: Goodwin
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bowden
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
authors.forename: Heinz
authors.initials: H
authors.lastname: Grunze
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.forename: Robin
authors.initials: R
authors.lastname: White
authors.forename: Paul
authors.initials: P
authors.lastname: Greene
authors.forename: Robert
authors.initials: R
authors.lastname: Leadbetter
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D016651:Lithium Carbonate / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D012008:Recurrence; D012720:Severity of Illness Index; D014227:Triazines / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D018692:Antimanic Agents; D014227:Triazines; D016651:Lithium Carbonate; D000077213:Lamotrigine