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

Dennis A. Revicki, Robert M.A. Hirschfeld, Eileen P. Ahearn, Richard H. Weisler, Cynthia Palmer, Paul E. Keck

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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 $28,911 for the divalproex group compared with $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 ($10,091 versus $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.

Original languageEnglish (US)
Pages (from-to)183-193
Number of pages11
JournalJournal of Affective Disorders
Issue number2-3
StatePublished - Jun 2005
Externally publishedYes


  • Bipolar disorder
  • Clinical trials
  • Cost-effectiveness analysis
  • Divalproex
  • Lithium

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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