title: The cost-effectiveness of lamotrigine in the maintenance treatment of adults with bipolar I disorder.
abstract: OBJECTIVE
  To present an economic model and cost-effectiveness estimates for lamotrigine in maintenance treatment of bipolar I disorder (BD-I) using outcomes from the pivotal lamotrigine trials. The main comparator treatments in the pivotal trials were lithium and .no maintenance. (acute-only) treatment. A comparison with olanzapine was included as an indirect analysis following publication of data during the course of our research.
  
  
  METHODS
  A Markov model was built around the 3 health states of euthymia, mania, and depression. The base-case model simulates a cohort of 1,000 patients with BD-I who have recently stabilized after resolution of a bipolar mania episode. The cohort was modeled for a period of 18 months. Resource-use estimates were derived from best available published data, treatment guidelines, a physician survey, and published unit cost data. Outputs were measured in terms of costs per acute mood episode avoided, costs per euthymic day gained, and costs per quality-adjusted life-years (QALYs). Direct health care payer costs are used in the analyses.
  
  
  RESULTS
  The base-case model for patients with a recent manic episode indicated that lamotrigine is the most effective treatment for avoiding both acute depression episodes and all types of acute episodes (depression and mania). It is also the most effective treatment in terms of number of euthymic days achieved (309 days per patient per year). Olanzapine is most effective for avoiding acute mania episodes. Total direct costs of treatment are lowest for the lithium treatment arm (Dollars 8,710 per patient for the 18-month period). All maintenance therapies were cost effective compared with the no-maintenance (acute-only treatment) arm. In the base case, lamotrigine had incremental cost-effectiveness ratios of Dollars 30 per euthymic day and Dollars 2,400 per acute episode avoided compared with lithium. A QALY analysis indicated that lamotrigine is cost effective in patients with a recent manic episode at Dollars 26,000 per QALY. The base-case model indicated that lamotrigine dominates olanzapine, (that is, lamotrigine costs less and is more effective than olanzapine) in patients with a recent manic episode. In a sensitivity analysis using outcomes from the pivotal trial of recently depressed patients, lamotrigine, in comparison with lithium, was not shown to be as cost effective as in the recently manic patients, but it was still cost effective compared with no maintenance treatment.
  
  
  CONCLUSIONS
  For a defined cohort of patients with BD-I, the pharmacoeconomic model indicated that prevention of mood episodes with lithium and lamotrigine is cost effective in patients with a recent manic, mixed, or hypomanic episode. The conclusions with respect to the indirect comparison with olanzapine should be validated if and when direct trial data become available. Cost-effectiveness of maintenance treatments for patients with BD-I (recently depressed as well as recently manic) are likely to improve in models with a broader costing perspective and that take a longer time frame. Further research into the outcome implications of health-related quality of life and other BD subgroups are recommended.
authors.affiliation: Fourth Hurdle Consulting Ltd., Holborn Tower, 137-144 High Holborn, London WC1V 6PL, UK. NeillCalvert@fourthhurdle.com
authors.forename: Neill W
authors.initials: NW
authors.lastname: Calvert
authors.forename: Steven P
authors.initials: SP
authors.lastname: Burch
authors.forename: Alex Z
authors.initials: AZ
authors.lastname: Fu
authors.forename: Penny
authors.initials: P
authors.lastname: Reeves
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000191:economics* / Q000627:therapeutic use; D018692:Antimanic Agents / Q000191:economics* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000191:economics / Q000627:therapeutic use; D001569:Benzodiazepines / Q000191:economics / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000191:economics*; D003362:Cost-Benefit Analysis; D006801:Humans; D000077213:Lamotrigine; D018020:Lithium Compounds / Q000191:economics / Q000627:therapeutic use; D018803:Models, Economic; D000077152:Olanzapine; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic; D014227:Triazines / Q000191:economics* / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D018020:Lithium Compounds; D014227:Triazines; D001569:Benzodiazepines; D000077152:Olanzapine; D000077213:Lamotrigine