title: Aripiprazole in combination with lamotrigine for the long-term treatment of patients with bipolar I disorder (manic or mixed): a randomized, multicenter, double-blind study (CN138-392).
abstract: OBJECTIVE
  To evaluate the efficacy and safety of aripiprazole (ARI) plus lamotrigine (LTG) compared with placebo (PBO) plus LTG, for long-term treatment in bipolar I disorder patients with a recent manic/mixed episode.
  
  
  METHODS
  After a 9-24 week stabilization phase receiving single-blind ARI (10-30 mg/day) plus open-label LTG (100 or 200 mg/day), patients maintaining stability (Young Mania Rating Scale/Montgomery-Åsberg Depression Rating Scale total scores ≤ 12) with ARI+LTG for eight consecutive weeks were randomized to continue on double-blind ARI + LTG or to receive PBO + LTG, after removing ARI from ARI + LTG treatment, and followed up for 52 weeks. The primary outcome measure was time from randomization to relapse into a manic/mixed episode.
  
  
  RESULTS
  A total of 787 patients entered the stabilization phase, and 351 were randomized to ARI + LTG (n = 178) or PBO + LTG (n = 173). ARI + LTG yielded a numerically longer time to manic/mixed relapse than PBO + LTG, but it was not statistically significant [hazard ratio (HR) = 0.55; 95% confidence interval (CI): 0.30-1.03; p = 0.058]. The estimated relapse rates at Week 52 were 11% for ARI + LTG and 23% for PBO + LTG, yielding a number needed-to-treat of nine (95% CI: 5-121). The three most common adverse events were akathisia [10.8%, 6.1% for ARI + LTG and PBO + LTG, respectively; number needed-to-harm (NNH) = 22], insomnia (7.4%, 11.5%), and anxiety (7.4%, 3.6%). Mean weight change was 0.43 kg and -1.81 kg, respectively (last observation carried forward, p = 0.001). Rates of ≥ 7% weight gain with ARI + LTG and PBO + LTG were 11.9% and 3.5%, respectively (NNH = 12).
  
  
  CONCLUSIONS
  ARI + LTG delayed the time to manic/mixed relapse but did not reach statistical significance. Safety and tolerability results revealed no unexpected adverse events for ARI combination with LTG.
authors.affiliation: Bristol-Myers Squibb, Plainsboro, NJ 0856-1616, USA. berit.carlson@bms.com
authors.forename: Berit X
authors.initials: BX
authors.lastname: Carlson
authors.forename: Terence A
authors.initials: TA
authors.lastname: Ketter
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Karen
authors.initials: K
authors.lastname: Timko
authors.forename: Robert D
authors.initials: RD
authors.lastname: McQuade
authors.forename: Raymond
authors.initials: R
authors.lastname: Sanchez
authors.forename: Estelle
authors.initials: E
authors.lastname: Vester-Blokland
authors.forename: Ronald
authors.initials: R
authors.lastname: Marcus
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole; D001714:Bipolar Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D015363:Quinolones / Q000627:therapeutic use*; D055502:Secondary Prevention; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use*
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D014227:Triazines; D000068180:Aripiprazole; D000077213:Lamotrigine