Role of Omega-3 fatty acids in preventing metabolic disturbances in patients on olanzapine plus either sodium valproate or lithium: a randomized double-blind placebo-controlled trial

This study was a randomized, double-blind, placebo-controlled, within-subject trial in adult psychiatric patients who were receiving olanzapine combined with lithium (Li) or valproate sodium (VPA). Omega-3 as fish oil with less than 1？g/day of EPA/DHA or its placebo was added to patients’ olanzapine and mood stabilizer regimens for 6？weeks. Metabolic parameters including anthropometric variables, lipid profile, metabolic syndrome indices, C-reactive protein, fibrinogen and lipoprotein (a) [(Lp) (a)] were assessed for participants.Forty one participants completed this study; 20 patients received omega-3 and 21 patients received placebo, added to their regimen of SGA and mood stabilizer. Omega-3 addition did not modulate anthropometric, metabolic syndrome and lipid parameter changes in 6？weeks. However, fibrinogen levels significantly decreased, Lp (a) did not increase and non-high-density lipoprotein cholesterol (non-HDL-C) did not go beyond its target level after omega-3 supplementation. Additionally, a significant inter-group effect was noted for Lp(a).This study suggests that use of short-term omega-3 supplementation added to a combined regimen of olanzapine and mood stabilizer may have a small modulating effect on some cardiovascular risk factors. Trials in longer periods of time and with larger number of patients are needed to further evaluate the effects of omega-3 supplements on preventing cardiovascular risk factors.This trial is registered at irct.ir and its Identifier is as following: IRCT138712231764N1Second generation antipsychotics (SGAs), in particular clozapine and olanzapine have been linked to excessive weight gain, dyslipidemia, hypertension and development of metabolic syndrome (MetS) [1]. Weight gain is also an unfavorable effect of valproate sodium (VPA) and lithium (Li) [2]. Moreover, VPA has been reported to be associated with dyslipidemia which is independent of weight gain [3]. Psychiatric patients often receive polypharmacy with antipsychoti