Tehran University of Medical Sciences Iranian Journal of Psychiatry 1735-4587 5 1 2010 03 15 18 22 Toktam Faghihi Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Padideh Ghaeli Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Psychiatry and Psychology Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran Adel Jahed Department of Endocrinology and Internal Medicine, Boo-ali University Hospital, Islamic Azad University, Tehran Medical Branch, Tehran, Iran Javad Mahmoudi-Gharaei Psychiatry and Psychology Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran Vandad Sharifi Department of Psychiatry, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran Akhondzadeh Shahin Psychiatry and Psychology Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran 2015 10 14 Objective: Metabolic side effects of the second generation (atypical) antipsychotics have been a forefront of attention since their availability. One common   concern   is   the   development   of   hyperglycemia   and   insulin resistance. The aim of this study was to evaluate the effect of early initiation of omega-3 fatty acids supplementation on glucose-insulin homeostasis in a group of psychiatric patients under treatment with olanzapine and sodium valproate or lithium combination. Method: In a double-blind design, eligible participants with schizophrenia, bipolar I, and schizoaffective disorders who were initiated on olanzapine combination  with  sodium  valproate  or  lithium were randomly assigned to receive omega-3 or identical placebo capsules for 6 weeks. Fasting blood sugar (FBS), insulin and HbA1c  were measured at the baseline and at the end of the 6th  week. Homeostatic model assessment of insulin resistance (HOMA-IR), as a measure of insulin resistance, was also determined at the same times. Results: At the end of the study, no significant difference was observed between the two arms in terms of FBS, fasting insulin, HbA1c and HOMA-IR. However, trends toward decreasing both fasting insulin levels (p= 0.06) and HOMA-IR  (p=  0.07)  were  noted  in  the  group  receiving  omega-3.  No significant  changes  in  the  outcome  variables  were  observed  from  the baseline to the final measurements in both groups. Conclusion: This study noted that adding omega-3 fatty acids at the commencement of olanzapine combination therapy with valproate or lithium could not favorably influence glucose-insulin homeostasis. However, trends toward a decrease in insulin levels (p= 0.06) and HOMA-IR (p= 0.07) observed in patients receiving omega-3 suggest a possible beneficial role of this supplement in this population and, therefore, warrant further evaluation. https://ijps.tums.ac.ir/index.php/ijps/article/view/380 https://ijps.tums.ac.ir/index.php/ijps/article/download/380/376