José A.S. Crippa, Department of Neuroscience and Behaviour, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Serdar M. Dursun, University of Romidepsin in vitro Alberta, Edmonton, Alberta, Canada. Glen B. Baker, University of Alberta, Edmonton, Alberta, Canada. Jaime E.C. Hallak, Department

of Neuroscience and Behaviour, Ribeirão Inhibitors,research,lifescience,medical Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Bipolar disorder (BD) is a chronic illness characterized by recurrent mood episodes resulting in profound negative effects on the interpersonal, social, family and vocational outcomes [Maj et al. 2000]. The economic burden of bipolar disorder is substantial. On average the annual National Health Service (NHS) cost of managing BD has been estimated to be approximately £200 million, of which hospital Inhibitors,research,lifescience,medical admissions accounted for 35% [Das Gupta and Guest, 2002]. The direct nonhealthcare cost was estimated to be approximately £90 million annually and the

indirect societal cost was estimated to be in the region of £1800 million annually. Medication is the cornerstone of the treatment for BD but is partially Inhibitors,research,lifescience,medical effective for most patients hence the need to evaluate new treatments. One potential treatment option is ethyl-eicosapentaenoic acid (ethyl-EPA). Frangou and colleagues conducted a 12-week double-blind trial to study the efficacy of ethyl-EPA as an adjunct treatment for bipolar disorder [Frangou et al. 2006]. The Markov model developed in Inhibitors,research,lifescience,medical this paper used the data from that study. Methods The clinical trial In this double-blinded placebo-controlled clinical trial outpatients with bipolar depression were randomly assigned to adjunctive Inhibitors,research,lifescience,medical treatment to mood stabilizers with placebo (n = 26) or with 1 g/day

(n = 24) or 2 g/day (n = 25) of ethyl-EPA. The demographic and clinical characteristics of the study participants are given in Table 1. The concomitant medication taken by the participants in each of the arms is given in Table 2. These characteristics did not differ significantly between groups, other than PDK4 for the use of antipsychotic medication (Fisher’s exact test, p = 0.01). The duration of the trial was 12 weeks and the primary outcome measure was changes in Hamilton Depression Rating Scale (HDRS) score [Hamilton, 1960]. The key finding was the depressive psychopathology as measured by the HDRS was lower by 3.3 (standard error [SE] = 1.40) points for the ethyl-EPA groups as compared with the placebo group. This difference was statistically significant (95% confidence interval [CI] -6.1 to -0.2, p = 0.03). In addition, patients in the placebo arm experienced a mean of 3 days in hospital (due to two patients being admitted) compared with a mean of zero for the ethyl-EPA arm, and this was not statistically significant.