Effectiveness and medical costs of divalproex versus lithium in the treatment of bipolar disorder: results of a naturalistic clinical trial

J Affect Disord. 2005 Jun;86(2-3):183-93. doi: 10.1016/j.jad.2005.01.002.


Objective: The clinical, quality of life (QOL), and medical cost outcomes of treatment with divalproex were compared with lithium in patients with bipolar I disorder over 1 year.

Methods: In a pragmatic, randomized clinical trial, 201 adults hospitalized with bipolar I manic or mixed episodes were randomized to divalproex or lithium, in addition to usual psychiatric care, and followed for 1 year. All subsequent treatment of bipolar disorder was managed by the patient's psychiatrist. Symptoms of mania and depression were evaluated at baseline and at hospital discharge. Assessments at the start of maintenance therapy and after 1, 3, 6, 9 and 12 months included manic and depressive symptoms, disability days and QOL. Medical resource use data were also collected monthly and costs were estimated using national sources.

Results: Divalproex-treated patients (12%) were less likely to discontinue study medications for lack of efficacy or adverse effects than lithium-treated patients (23%). No statistically significant differences between the treatment groups were observed over the 1-year maintenance phase for clinical symptoms, QOL outcomes, or disability days. Mean estimated total medical costs were USD 28,911 for the divalproex group compared with USD 30,666 for the lithium treatment group. Patients continuing mood stabilizer therapy at 3 months had slightly better health outcomes and substantially lower total medical costs than those who discontinued therapy ( USD 10,091 versus USD 34,432, respectively).

Conclusions: Divalproex maintenance treatment for bipolar disorder resulted in comparable medical costs, clinical and QOL outcomes compared with lithium. Patients remaining on mood stabilizer therapy had substantially lower total medical costs and better health outcomes compared with those who discontinued therapy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticonvulsants / therapeutic use
  • Antimanic Agents / economics*
  • Antimanic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / economics
  • Carbamazepine / economics
  • Carbamazepine / therapeutic use
  • Drug Costs
  • Drug Therapy, Combination
  • Female
  • Health Care Costs*
  • Health Status
  • Hospitalization
  • Humans
  • Lithium / economics*
  • Lithium / therapeutic use*
  • Male
  • Outcome Assessment, Health Care
  • Quality of Life
  • Treatment Outcome
  • Valproic Acid / economics*
  • Valproic Acid / therapeutic use*


  • Anticonvulsants
  • Antimanic Agents
  • Carbamazepine
  • Valproic Acid
  • Lithium