The effects of eicosapentaenoic acid in tardive dyskinesia: A randomized, placebo-controlled trial Robin Emsley a, * , Dana J.H. Niehaus a , Liezl Koen a , Piet P. Oosthuizen a , H. Jadri Turner a , Paul Carey a , Susan Janse van Rensburg b , J. Stefan Maritz c , Harald Murck d a Department of Psychiatry, Faculty of Health Sciences, University of Stellenbosch, PO Box 19063, Tygerberg 7505, Cape Town, South Africa b Department of Chemical Pathology, Faculty of Health Sciences, University of Stellenbosch,Tygerberg 7505, Cape Town, South Africa c Medical Research Council Institute of Biostatistics, Cape Town, South Africa d Amarin Neuroscience Limited, Kings Park House, Laurelhill Business Park, Stirling, FK7 9JQ, United Kingdom Received 25 January 2006; received in revised form 7 March 2006; accepted 9 March 2006 Available online 24 April 2006 Abstract Objective: Worldwide, conventional antipsychotic medication continues to be used extensively, and tardive dyskinesia (TD) remains a serious complication. The primary objective of the present study was to compare the efficacy of EPA versus placebo in reducing symptoms of TD. Method: This was a 12-week, double-blinded, randomized study of ethyl-EPA 2g/day versus placebo as supplemental medication, in patients with schizophrenia or schizoaffective disorder, with established TD. Results: Eighty-four subjects were randomized, of whom 77 were included in the analysis. Both the EPA and placebo groups displayed significant baseline to endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores, but there were no significant between-group differences ( p = 0.4). Response rates (z 30% improvement in TD symptoms) also did not differ significantly between EPA-treated subjects (45%) and placebo-treated subjects (32%) ( p = 0.6). However, a post-hoc linear mixed model repeated measures analysis of variance indicated an effect for treatment group and duration of TD. The EPA-treated patients had significantly greater mean reductions in dyskinesia scores initially, although this was not sustained beyond 6 weeks. Conclusions: This trial failed to demonstrate an antidyskinetic effect for ethyl-EPA 2g/day on the primary efficacy measure. However, a modest and transient benefit is suggested in patients with more recent onset of TD. The lack of clear-cut efficacy could be explained on the basis of the dose of EPA being too low, the study being underpowered, TD being too chronic in the majority of cases, differences in dietary fatty acid intake, or that EPA lacks an antidyskinetic action. D 2006 Elsevier B.V. All rights reserved. Keywords: Eicosapentaenoic acid; Essential fatty acids; Tardive dyskinesia; Movement disorder; Randomized controlled trial; Schizophrenia 0920-9964/$ - see front matter D 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2006.03.023 * Corresponding author. Tel.: +27 21 9389227. E-mail address: rae@sun.ac.za (R. Emsley). Schizophrenia Research 84 (2006) 112 – 120 www.elsevier.com/locate/schres