1. ¹Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, USA
2. ²Abbott Laboratories, Abbott Park, IL, USA
3. ³Department of Biological Psychiatry, University of Cincinnati, Cincinnati, OH, USA
4. ⁴University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, OH, USA
5. ⁵University of Texas Health Science Center-Houston, Houston, TX, USA
6. ⁶University of North Carolina School of Medicine, Chapel Hill, NC, USA
7. ⁷Duke University Medical Center, Durham, NC, USA

Correspondence: Dr CL Bowden, Department of Psychiatry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. Tel: +1 210 567 5405; Fax: +1 210 567 3759; E-mail: bowdenc@uthscsa.edu

Received 1 September 2004; Revised 24 February 2005; Accepted 29 March 2005; Published online 8 June 2005.

Abstract

Euphoric and mixed (dysphoric) manic symptoms have different response patterns to divalproex and lithium in acute mania treatment, but have not been studied in relationship to maintenance treatment outcomes. We examined the impact of initial euphoric or dysphoric manic symptomatology on maintenance outcome. Randomized maintenance treatment with divalproex, lithium, or placebo was provided for 372 bipolar I patients, who met improvement criteria during open phase treatment for an index manic episode. The current analysis grouped patients according to the index manic episode subtype (euphoric or dysphoric), and evaluated the impact on maintenance treatment outcome. The rate of early discontinuation due to intolerance during maintenance treatment was higher for initially dysphoric patients (N=249) than euphoric patients (N=123; 15.7 vs 7.3%, respectively; p=0.032). Both lithium (23.2%) and divalproex (17.1%) were associated with more premature discontinuations due to intolerance than placebo (4.8%; p=0.003 and 0.02, respectively) in the initially dysphoric patients. Among initially euphoric patients, treatment with lithium was associated with significantly more premature discontinuations due to intolerance compared to placebo (18.2 vs 0%; p=0.03), and divalproex was significantly (p=0.05) more effective than lithium, but not placebo in delaying time to a depressive episode. Initial euphoric mania appeared to predispose to better outcomes on indices of depression and overall function with divalproex maintenance than with either placebo or lithium. Dysphoric mania appeared to predispose patients to more side effects when treated with either divalproex or lithium during maintenance therapy.