Potential effects of omega-3 fatty acids on anemia and inflammatory markers in maintenance hemodialysis patients Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Improvement of Major Depression is Associated with Increased Erythrocyte DHA Effects of Omega-3 Fatty Acids on Depression and Quality of Life in Maintenance Hemodialysis Patients Omega-3 fatty acids in major depressive disorder: A preliminary double-blind, placebo-controlled trial Inflammation and treatment response to sertraline in patients with coronary heart disease and comorbid major depression. Biological Effects of Add-On Eicosapentaenoic Acid Supplementation in Diabetes Mellitus and Co-Morbid Depression: A Randomized Controlled Trial Comparison between the AA/EPA ratio in depressed and non depressed elderly females: omega-3 fatty acid supplementation correlates with improved symptoms but does not change immunological parameters The effect of docosahexaenoic acid on plasma catecholamine concentrations and glucose tolerance during long-lasting psychological stress: a double-blind placebo-controlled study. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Long chain omega 3 polyunsaturated fatty acids supplementation in the treatment of elderly depression: Effects on depressive symptoms, on phospholipids fatty acids profile and on health-related quality of life Effect of Omega-3 Fatty Acids Supplementation on Depressive Symptoms and on Health-Related Quality of Life in the Treatment of Elderly Women with Depression: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial Omega-3 augmentation of sertraline in treatment of depression in patients with coronary heart disease: a randomized controlled trial. The effect of omega-3 fatty acids on depressive symptoms and inflammatory markers in maintenance hemodialysis patients: a randomized, placebo-controlled clinical trial Omega-3 Fatty Acid Augmentation of Citalopram Treatment for Patients With Major Depressive Disorder Inflammation as a Predictive Biomarker for Response to Omega-3 Fatty Acids in Major Depressive Disorder: A Proof of Concept Study No clear evidence of an association between plasma concentrations of n-3 long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population. Dietary alpha-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients. Eicosapentaenoic acid as an add-on to antidepressant medication for co-morbid major depression in patients with diabetes mellitus: a randomized, double-blind placebo-controlled study. A double-blind, randomized controlled clinical trial comparing eicosapentaenoic acid versus docosahexaenoic acid for depression. The efficacy of omega-3 supplementation for major depression: a randomized controlled trial. Risk of postpartum depression in relation to dietary fish and fat intake in Japan: the Osaka Maternal and Child Health Study. Neuroticism but not omega-3 fatty acid levels correlate with early responsiveness to escitalopram. Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Depletion of Omega-3 Fatty Acid Levels in Red Blood Cell Membranes of Depressive Patients Obstructive sleep apnea/hypopnea syndrome and poor response to sertraline in patients with coronary heart disease. A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Supplementation of n-3 Polyunsaturated Fatty Acids for Major Depressive Disorder: A Randomized, Double-Blind, 12-Week, Placebo-Controlled Trial in Korea Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Double-Blind, Randomized, Placebo-Controlled Trials of Ethyl-Eicosapentanoate in the Treatment of Bipolar Depression and Rapid Cycling Bipolar Disorder Omega-3 fatty acid treatment and T(2) whole brain relaxation times in bipolar disorder. A double-blind, randomized controlled trial of ethyl-eicosapentaenoate for major depressive disorder. Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression. Fish oil supplementation in the treatment of major depression: A randomised double-blind placebo-controlled trial A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Supplementation with Eicosapentaenoic Omega-3 Fatty Acid Does Not Influence Serum Brain-Derived Neurotrophic Factor in Diabetes Mellitus Patients with Major Depression: A Randomized Controlled Pilot Study Youth depression alleviation: the Fish Oil Youth Depression Study (YoDA-F): A randomized, double-blind, placebo-controlled treatment trial. Comparison of Therapeutic Effects of Omega-3 Fatty Acid Eicosapentaenoic Acid and Fluoxetine, Separately and in Combination, in Major Depressive Disorder Effects of ethyl-eicosapentaenoic acid omega-3 fatty acid supplementation on hot flashes and quality of life among middle-aged women: a double-blind, placebo-controlled, randomized clinical trial
Background Anemia is a common complication among hemodialysis ( HD ) patients . Although intravenous iron and erythropoiesis-stimulating agents revolutionized anemia treatment , about 10 % of HD patients show suboptimal response to these agents . Systemic inflammation and increased serum hepcidin level may contribute to this hyporesponsiveness . Considering the anti-inflammatory properties of omega-3 fatty acids , this study aim ed to evaluate potential role of these fatty acids in improving anemia and inflammation of chronic HD patients . Methods In this r and omized , placebo-controlled trial , 54 adult patients with HD duration of at least 3 months were r and omized to ingest 1800 mg of either omega-3 fatty acids or matching placebo per day for 4 months . Anemia parameters including blood hemoglobin , serum iron , transferrin saturation ( TSAT ) , erythropoietin resistance index , and required dose of intravenous iron and erythropoietin , and serum concentrations of inflammatory/anti-inflammatory markers including interleukin (IL)-6 , tumor necrosis factor (TNF)-α , IL-10 , C-reactive protein ( CRP ) , hepcidin , ferritin , intact parathyroid hormone ( iPTH ) , and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and after 4 months of the intervention . Results 45 subjects ( 25 in the omega-3 and 20 in the placebo group ) completed the study . No significant changes were observed in blood hemoglobin , serum iron , TSAT , and required dose of intravenous iron in either within or between group comparisons . Additionally , erythropoietin resistance index as well as required dose of intravenous erythropoietin showed no significant change in the omega-3 group compared to the placebo group . Although a relative alleviation in inflammatory state appeared in the omega-3 group , the mean differences of inflammatory and anti-inflammatory markers between the two groups did not reach statistically significant level except for IL-10-to-IL-6 ratio and serum ferritin level which showed significant changes in favor of omega-3 treatment ( P < 0.001 and P = 0.003 , respectively ) . Conclusion Omega-3 fatty acids relatively improved systemic inflammation of chronic HD patients without any prominent benefits on anemia . However , future well- design ed studies on larger number of patients may determine utility of omega-3 fatty acids in HD patients with respect to inflammation and anemia BACKGROUND Psychological distress ( PD ) and depressive symptoms are commonly observed during menopausal transition . Studies suggest that omega-3 ( n-3 ) fatty acids may help alleviate depression . OBJECTIVE The objective was to compare enriched ethyl-eicosapentaenoic acid ( E-EPA ) supplementation with placebo for the treatment of PD and depressive symptoms in middle-aged women . DESIGN Women with moderate-to-severe PD ( n = 120 ) were r and omly assigned to receive 1.05 g E-EPA/d plus 0.15 g ethyl-docosahexaenoic acid/d ( n = 59 ) or placebo ( n = 61 ) for 8 wk . The main outcomes were 8-wk changes in PD scores [ Psychological General Well-Being Schedule ( PGWB ) ] and depressive scales [ 20-item Hopkins Symptom Checklist Depression Scale ( HSCL-D-20 ) and the 21-item Hamilton Depression Rating Scale ( HAM-D-21 ) ] . RESULTS At baseline , women with PD were mildly to moderately depressed , and 24 % met the major depressive episode ( MDE ) criteria of the Diagnostic and Statistical Manual of Mental Disorders , 4th edition . After 8 wk , outcomes improved in both groups , but no significant differences were noted between them . Stratification analyses for MDE diagnosis at baseline indicated that differences in adjusted 8-wk changes between the E-EPA group without MDE ( n = 46 ) and the placebo group ( n = 45 ) were 8.0 ( 95 % CI : 0.6 , 15.3 ; P = 0.034 ) for the PGWB , -0.2 ( 95 % CI : -0.01 , -0.4 ; P = 0.040 ) for the HSCL-D-20 , and -2.7 ( 95 % CI : -0.3 , -5.1 ; P = 0.030 ) for the HAM-D-21 . Differences in adjusted 8-wk changes between the E-EPA group with MDE ( n = 13 ) and the placebo group ( n = 16 ) were not significant . CONCLUSIONS To our knowledge , this is the first trial of n-3 supplementation in the treatment of PD and depressive symptoms in middle-aged women . In women with PD without MDE at baseline , the 8-wk changes in PD and depressive scales improved significantly more with E-EPA than with placebo . This trial was registered at http://www.controlled-trials.com as IS RCT N69617477 The aim of this study was to determine if changes in omega-3 polyunsaturated fatty acid status following tuna oil supplementation correlated with changes in scores of depression . A total of 95 volunteers receiving treatment for major depression were r and omised to consume 8 × 1 g capsules per day of HiDHA ( 2 g DHA , 0.6 g EPA and 10 mg Vitamin E ) or olive oil ( placebo ) for 16 weeks , whilst undergoing weekly counseling sessions by trained clinical psychologists using a st and ard empirically vali date d psychotherapy . Depression status was assessed using the 17 item Hamilton rating scale for depression and the Beck Depression Inventory by a psychodiagnostician who was blind to the treatment . Blood was taken at baseline and 16 weeks ( n = 48 ) for measurement of erythrocyte fatty acids .  With HiDHA supplementation , erythrocyte DHA content rose from 4.1 ± 0.2 to 7.9 ± 0.4 % ( mean ± SEM , p < 0.001 ) of total fatty acids but did not change ( 4.0 ± 0.2 to 4.1 ± 0.2 % ) in the olive oil group . The mean changes in scores of depression did not differ significantly between the two groups ( −12.2 ± 2.1 for tuna oil and −14.4 ± 2.3 for olive oil ) . However , analysis of covariance showed that in the fish oil group there was a significant correlation ( r = −0.51 ) between the change in erythrocyte DHA and the change in scores of depression ( p < 0.05 ) . Further study of the relationship between DHA and depression is warranted Depression and health-related quality of life ( HRQoL ) are closely interrelated among hemodialysis ( HD ) patients and associated with negative impacts on patients ' clinical outcomes . Considering previous reports on clinical benefits of omega-3 fatty acids in major depression and HRQoL in other patient population s , this study examined effects of omega-3 fatty acids on depression and HRQoL in chronic HD patients . In this r and omized placebo-controlled trial , 40 adult patients with a Beck Depression Inventory ( BDI ) score of ≥16 and HD vintage of at least 3 months were r and omized to ingest 6 soft-gel capsules of either omega-3 fatty acids ( 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid in each capsule ) or corresponding placebo , daily for 4 months . At baseline and after 4 months , 2 question naires of BDI and the Medical Outcome Study 36-Item Short-Form Health Survey were completed by each patient . Although baseline BDI score was comparable between the 2 groups , it was significantly lower in the omega-3 group compared with the placebo group at the end of the study ( P = 0.008 ) . Except for mental health , social functioning , and general health , other domains of HRQoL showed significant improvement in the omega-3 group compared with the placebo group at month 4 of the study ( P < 0.05 for all ) . Regression analysis revealed that ameliorated BDI score by omega-3 treatment had considerable role in the improvement of overall HRQoL score , physical and mental component dimensions , and score of physical functioning , role-physical , and bodily pain . Supplemental use of omega-3 fatty acids  in HD patients with  depressive symptoms seems to be efficacious in improving depressive symptoms and Patients with depression have been extensively reported to be associated with the abnormality of omega-3 polyunsaturated fatty acids ( PUFAs ) , including significantly low eicosapentaenoic acid and docosahexaenoic acid in cell tissue contents ( red blood cell membrane , plasma , etc . ) and dietary intake . However , more evidence is needed to support its relation . In this study , we conducted an 8-week , double-blind , placebo-controlled trial , comparing omega-3 PUFAs ( 6.6 g/day ) [ corrected ] with placebo , on the top of the usual treatment , in 28 patients with major depressive disorder . Patients in the omega-3 PUFA group had a significantly decreased score on the 21-item Hamilton Rating Scale for Depression than those in the placebo group ( P < 0.001 ) . From the preliminary findings in this study , omega-3 PUFAs could improve the short-term course of illness and were well tolerated in patients with major depressive disorder OBJECTIVE Treatment-resistant depression has recently emerged as a marker of increased risk for morbidity and mortality in patients with coronary heart disease ( CHD ) . Studies in depressed patients without CHD suggest that elevated markers of inflammation predict poor response to treatment . This may help to explain the increased risk of cardiac events associated with depression . We therefore studied the relationship between pretreatment markers of inflammation and treatment response in patients with CHD and major depression . METHODS This was a planned , secondary analysis of a clinical trial in which 122 patients with CHD and comorbid major depression were r and omly assigned to 50 mg of sertraline plus 2 g/day omega-3 fatty acids or to 50 mg of sertraline plus 2 g/day corn oil placebo capsules for ten weeks . Depressive symptoms were assessed with the Beck Depression Inventory-II ( BDI-II ) . Blood sample s were collected at baseline to determine levels of high-sensitivity C-reactive protein ( hs-CRP ) , interleukin-6 ( IL-6 ) , and tumor necrosis factor alpha ( TNF-α ) . The primary outcome was the post-treatment BDI-II depression score . RESULTS Baseline levels of hs-CRP , IL-6 , and TNF-α were not associated with the 10-week post-treatment depression score ( P=.89 , P=.88 , and P=.31 , respectively ) . Treatment responders ( > 50 % reduction from baseline BDI-II score ) did not differ from non-responders in either baseline hs-CRP , IL-6 , or TNF-α ( P=.83 , P=.93 , and P=.24 , respectively ) . Similarly , depression remitters ( BDI-II ≤8 at post-treatment ) did not differ from non-remitters on the three baseline inflammation markers . CONCLUSION These findings do not support the hypothesis that elevated baseline inflammatory markers predict poor response to sertraline in patients with CHD and major depression . The explanation for the increased risk of cardiac events associated with poor response to depression treatment remains unclear Background Eicosapentaenoic acid ( EPA ) may reduce increased risks for ( cardiovascular ) morbidity and mortality in patients with diabetes mellitus ( DM ) and comorbid major depressive depression ( MDD ) . Yet , effects of EPA-supplementation on biological risk factors for adverse outcomes have not been studied in DM- patients with MDD . Methods We performed a r and omized , double-blind trial ( n = 25 ) comparing add-on ethyl-EPA-supplementation to placebo on ( I ) oxidative stress , ( II ) inflammatory , ( III ) hypothalamic-pituitary-adrenal (HPA)-axis , ( IV ) one-carbon-cycle , ( V ) fatty acid metabolism and ( VI ) lipoprotein parameters during 12-weeks ' follow-up . Results Besides increases in supplemented α-tocopherol [ estimate ( 95 % CI ) ; 3.62 ( 1.14–6.11 ) µmol/l ; p = 0.006 ] and plasma and erythrocyte EPA , the intervention did not influence other oxidative stress , inflammatory or one-carbon-cycle parameters compared to placebo . HPA-axis reactivity significantly decreased in the EPA-group ( N = 12 ) [ AUCi : −121.93 ( −240.20–−3.47 ) min × nmol/l ; p = 0.045 ] , not in the placebo-group ( N = 12 ) . Furthermore , EPA-supplementation increased erythrocyte and plasma docosapentaenoic acid , and decreased plasma arachidonic acid ( AA ) concentrations [ −1.61 ( −3.10–−0.11 ) % ; p = 0.036 ] . Finally , EPA had a multivariate influence on lipoprotein concentrations ( p = 0.030 ) , reflected by relative increases in high density lipoprotein [ HDL ; 0.30 ( 0.02–0.58 ) mmol/l ; p = 0.039 ] and total cholesterol concentrations [ 1.01 ( 0.29–1.72 ) mmol/l ; p = 0.008 ] . Conclusion Overall , add-on EPA-supplementation had limited effects on biological risk factors for adverse outcome in this sample of DM- patients with comorbid MDD . Besides increases in concentrations of supplemented α-tocopherol and EPA , AA decreased , and inconclusive effects on HPA-axis (re)activity and lipoprotein concentrations were observed . Therefore , further studies on the alleged beneficial effects of EPA-supplementation on biological risk factors for adverse outcome in DM- patients with comorbid MDD seem warranted , preferably using clinical outcomes such as ( cardiovascular ) DM-complications . Trial Registration Controlled-Trials.com IS RCT N30877831 IS RCT Background Depression is one of the most frequently missed diagnoses in elderly people , with obvious negative effects on quality of life . Various studies have shown that long chain omega-3 polyunsaturated fatty acids ( n-3 PUFA ) may be useful in its management . Our objective was to evaluate whether a supplement containing n-3 PUFA improves depressive symptoms in depressed elderly patients , and whether the blood fatty acid pattern is correlated with these changes . Methods The severity of depressive symptoms according to the Geriatric Depression Scale ( GDS ) , blood fatty acid composition and erythrocyte phospholipids were analyzed in 46 depressed females aged 66 - 95y , diagnosed with depression according to DSMIV , within the context of a r and omized , double-blind , placebo-controlled trial . 22 depressed females were included in the intervention group ( 2.5 g/day of n-3 PUFA for 8 weeks ) , and 24 in the  placebo  group . We also measured immunological parameters ( CD2 , CD3 , CD4 , CD8 , CD16 , CD19 and cytokines ( IL-5 , IL-15 ) . Results The mean GDS score and AA/EPA ratio , in whole blood and RBC membrane phospholipids , were significantly lower after 2 months supplementation with n-3 PUFA . A significant correlation between the amelioration of GDS and the AA/EPA ratio with some immunological parameters , such as CD2 , CD19 , CD4 , CD16 and the ratio CD4/CD8 , was also found . Nevertheless , omega-3 supplementation did not significantly improve the studied immunological functions . Conclusions n-3 PUFA supplementation ameliorates symptoms in elderly depression . The n-3 PUFA status may be monitored by means of the determination of whole blood AA/EPA ratio We previously found that docosahexaenoic acid ( DHA ) intake prevented aggression from increasing at times of mental stress . In the present study , we investigated whether DHA intake modified the plasma catecholamines and cortisol of medical students during a 9-wk period of final exams . We also investigated the effects of DHA intake on a 75 g oral glucose tolerance test ( oGTT ) . Fourteen medical students participated in the present study . They were r and omly allocated to either control or DHA group in a double-blind manner . Subjects in the control group ( 4 males and 3 females ) took 10 control capsules/d , each capsule containing 280 mg of mixed plant oil , and those in the  DHA  group ( 4 males and 3 females ) took 10 DHA capsules/d containing 1.5 g DHA for 9 wk , during which subjects underwent more than 20 stressful final exams . At the start and end of the study , plasma catecholamines ( epinephrine , norepinephrine ( NE ) and dopamine ) and cortisol were measured ; a 75 g oGTT was also performed . There were no intra- or intergroup differences in plasma glucose concentrations . However , NE concentrations were significantly reduced after DHA administration ( -31 % , p < 0.03 ) . The other catecholamines and cortisol did not change significantly . The plasma ratio of epinephrine to NE increased in every DHA subject ( + 78 % , p < 0.02 ) , and intergroup differences were significant ( p < 0.03 ) . We conclude that these effects of DHA may be applied to people under long-lasting psychological stress to prevent stress-related diseases BACKGROUND Omega3 fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate , 2 effective treatments for bipolar disorder . The present study was performed to examine whether omega3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder . METHODS A 4-month , double-blind , placebo-controlled study , comparing omega3 fatty acids ( 9.6 g/d ) vs placebo ( olive oil ) , in addition to usual treatment , in 30 patients with bipolar disorder . RESULTS A Kaplan-Meier survival analysis of the cohort found that the  omega3 fatty acid  patient group had a significantly longer period of remission than the placebo group ( P = .002 ; Mantel-Cox ) . In addition , for nearly every other outcome measure , the omega3 fatty acid group performed better than the placebo group . CONCLUSION Omega3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder Objective Recent observations showed that long chain omega 3 polyunsaturated fatty acids ( n-3 LCPUFA ) could represent a potential treatment for elderly depression . To determine if a n-3 LCPUFA containing supplement improves depressive symptoms , changes phospholipids acids profile and ameliorates Health related quality of life ( HRQoL ) in depressed elderly patients . Design Two-months , r and omized , double-blind , placebo-controlled trial . Setting Nursing home in Pavia , Italy . SubjectsForty-six depressed females , aged 66–95 years . Intervention22 depressed females were included in the  intervention group ( n-3 group , that received 2.5 g/day of n-3 LCPUFA , with 1.67 grams of EPA and 0.83 grams of DHA ) , and 24 patients in the placebo group . The primary endpoint was the improvement of depressive symptoms as evaluated by Geriatric Depression Scale ( GDS ) . Secondary endpoints were the evaluation of modifications of erythrocyte membrane phospholipids fatty acid profile and of of HRQoL , by using the Short-Form 36-Item Health Survey ( SF-36 ) . All parameters were assessed before and after the treatment period of 8 weeks . Results The mean GDS at 2 months was significantly lowered only for the n-3 group . SF-36 physical and mental components were significantly increased in the intervention group . Compliance was good , as confirmed by erythrocyte membrane phospholipid FA concentrations , with significant increase of EPA and DHA in the intervention group . Conclusion The supplementation of n-3 LCPUFA in elderly female patients reduces the occurrence of depressive symptoms , improves phospholipids fatty acids profile and healthrelated quality of life Objective : In elderly individuals , depression is one of the most frequently missed diagnoses with negative effects on quality of life . The authors investigated whether a supplement containing long-chain omega-3 polyunsaturated fatty acids ( n-3 LCPUFA ) improves depressive symptoms and health-related quality of life ( HRQoL ) in depressed elderly patients . Design : Eight-week , r and omized , double-blind , placebo-controlled trial . Setting : Nursing home in Pavia , Italy . Participants : Forty-six depressed women , aged 66–95 years . Intervention : Twenty-two depressed women were included in the intervention group ( n-3 group , which received 2.5 g/d of n-3 LCPUFA , with 1.67 g of eicosapentaenoic acid [ EPA ] and 0.83 g of docosahesaenoic acid [ DHA ] ) , and 24 patients were included in the placebo group . The primary endpoint was the improvement of depressive symptoms , as evaluated by the Geriatric Depression Scale ( GDS ) . Secondary endpoints were the evaluation of HRQoL , by using the Short-Form 36-Item Health Survey ( SF-36 ) , and modifications of erythrocyte membrane phospholipids fatty acid profile . All variables were assessed before and after the treatment period of 8 weeks . Results : The mean GDS at 8 weeks was significantly lower compared with the n-3 group . The SF-36 physical and mental components were significantly increased in the intervention group . Compliance was good , as confirmed by erythrocyte membrane phospholipid FA concentrations , with a significant increase of EPA and DHA in the intervention group . Conclusion : Supplementation with n-3 LCPUFA is efficacious in the amelioration of depressive symptoms and quality of life in the treatment of depressed elderly female patients CONTEXT Studies of depressed psychiatric patients have shown that antidepressant efficacy can be increased by augmentation with omega-3 fatty acids . OBJECTIVE To determine whether omega-3 improves the response to sertraline  in patients with major depression and coronary heart disease ( CHD ) . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial . Between May 2005 and December 2008 , 122 patients in St Louis , Missouri , with major depression and CHD were r and omized . INTERVENTIONS After a 2-week run-in period , all patients were given 50 mg/d of sertraline and r and omized in double-blind fashion to receive 2 g/d of omega-3 acid ethyl esters ( 930 mg of eicosapentaenoic acid [ EPA ] and 750 mg of docosahexaenoic acid [ DHA ] ) ( n=62 ) or to corn oil placebo capsules ( n=60 ) for 10 weeks . MAIN OUTCOME MEASURES Scores on the Beck Depression Inventory ( BDI-II ) and the Hamilton Rating Scale for Depression ( HAM-D ) . RESULTS Adherence to the medication regimen was 97 % or more in both groups for both medications . There were no differences in weekly BDI-II scores ( treatment x time interaction = 0.02 ; 95 % confidence interval [ CI ] , -0.33 to 0.36 ; t(112 ) = 0.11 ; P = .91 ) , pre-post BDI-II scores  ( placebo , 14.8 vs omega-3 , 16.1 ; 95 % difference-in-means CI , -4.5 to 2.0 ; t(116 ) = -0.77 ; P = .44 ) , or HAM-D scores ( placebo , 9.4 vs omega-3 , 9.3 ; 95 % difference-in-means CI , -2.2 to 2.4 ; t(115 ) = 0.12 ; P = .90 ) . The groups did not differ on predefined indicators of depression remission ( BDI-II < or = 8 : placebo , 27.4 % vs omega-3 , 28.3 % ; odds ratio [ OR ] , 0.96 ; 95 % CI , 0.43 - 2.15 ; t(113 ) = -0.11 ; P = .91 ) or response ( > 50 % reduction in BDI-II from baseline : placebo , 49.0 % vs omega-3 , 47.7 % ; OR , 1.06 ; 95 % CI , 0.51 - 2.19 ; t(112 ) = 0.15 ; P = .88 ) . CONCLUSIONS Treatment of patients with CHD and major depression with sertraline and omega-3 fatty acids did not result in superior depression outcomes at 10 weeks , compared with sertraline and placebo . Whether higher doses of omega-3 or sertraline , a different ratio of EPA to DHA , longer treatment , or omega-3 monotherapy can improve depression in patients with CHD remains to be determined . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00116857 Purpose This study was design ed to investigate the effects of omega-3 fatty acids on depression and chronic inflammation in hemodialysis patients . Method Fifty-four maintenance hemodialysis patients were r and omized to ingest two omega-3 ( each containing 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid ) or placebo capsules , three times daily for 4 months . Main outcome measures : Beck Depression Inventory ( BDI ) score and serum levels of C-reactive protein ( CRP ) , interleukin (IL)-6 , IL-10 , tumor necrosis factor (TNF)-α , ferritin , intact parathyroid hormone ( iPTH ) , and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and at the end of the study . Results Omega-3 supplement  lowered BDI score significantly after 4 months of intervention . Among pro- and anti-inflammatory mediators , only serum ferritin level and IL-10 to IL-6 ratio showed significant changes in favor of omega-3 supplement during the study . In linear regression model adjusted for baseline values , omega-3 treatment was a significant predictor of reduced serum CRP , ferritin , and iPTH levels , and increased IL-10 to IL-6 ratio . No significant association was found between the anti-inflammatory and anti-depressant effects  of omega-3 supplement . Conclusions Supplemental use of omega-3 fatty acids decreases depressive symptoms in hemodialysis patients apart from their anti-inflammatory effects Objective The objective of this study was to explore the efficacy of combination therapy with citalopram plus omega-3 fatty acids versus citalopram plus placebo ( olive oil ) in the initial treatment of individuals with major depressive disorder ( MDD ) . We hypothesized that combination therapy would lead not only to greater efficacy but also to a more rapid onset of therapeutic response . Methods Forty-two subjects participated in this 9-week r and omized , masked , placebo-controlled study of combination therapy ( two 1 g capsules containing a blend of 900 mg of eicosapentaenoic acid , 200 mg of and docosahexaenoic acid , and 100 mg of other omega-3 fatty acids twice daily plus citalopram ) versus monotherapy ( two 1 g capsules of olive oil per day plus citalopram ) treatment of MDD . Results The combination therapy demonstrated significantly greater improvement in Hamilton Depression Rating scale scores over time ( F = 7.32 ; df 1,177 ; P = 0.008 ) beginning at week 4 ( t = −2.48 ; df 177 ; P = 0.014 ) . Conclusions Combination therapy was more effective than monotherapy in decreasing signs and symptoms of MDD during the 8 weeks of active treatment ; however , combination therapy did not seem to enhance the speed of the initial antidepressant response . These findings suggest that there may be an advantage to combining omega-3 fatty acids with a selective serotonin uptake inhibitor in the initial treatment of individuals with MDD . A larger definitive study is warranted This study explores whether inflammatory biomarkers act as moderators of clinical response to omega-3 ( n-3 ) fatty acids in subjects with major depressive disorder ( MDD ) . One hundred fifty-five subjects with Diagnostic and Statistical Manual of Mental Disorders , 4th Edition ( DSM-IV ) MDD , a baseline 17-item Hamilton Depression Rating Scale ( HAM-D-17 ) score ⩾15 and baseline biomarker data ( interleukin (IL)-1ra , IL-6 , high-sensitivity C-reactive protein ( hs-CRP ) , leptin and adiponectin ) were r and omized between 18 May 2006 and 30 June 2011 to 8 weeks of double-blind treatment with eicosapentaenoic acid (EPA)-enriched n-3 1060 mg day−1 , docosahexaenoic acid (DHA)-enriched n-3 900 mg day−1 or placebo . Outcomes were determined using mixed model repeated measures analysis for ‘ high ’ and ‘ low ’ inflammation groups based on individual and combined biomarkers . Results are presented in terms of st and ardized treatment effect size ( ES ) for change in HAM-D-17 from baseline to treatment week 8 . Although overall treatment group differences were negligible ( ES=−0.13 to + 0.04 ) , subjects with any ‘ high ’ inflammation improved more on EPA than placebo ( ES=−0.39 ) or DHA ( ES=−0.60 ) and less on DHA than placebo ( ES=+0.21 ) ; furthermore , EPA-placebo separation increased with increasing numbers of markers of high inflammation . Subjects r and omized to EPA with ‘ high ’ IL-1ra or hs-CRP or low adiponectin ( ‘ high ’ inflammation ) had medium ES decreases in HAM-D-17 scores vs subjects ‘ low ’ on these biomarkers . Subjects with ‘ high ’ hs-CRP , IL-6 or leptin were less placebo-responsive than subjects with low levels of these biomarkers ( medium to large ES differences ) . Employing multiple markers of inflammation facilitated identification of a more homogeneous cohort of subjects with MDD responding to EPA vs placebo in our cohort . Studies are needed to replicate and extend this proof-of-concept work Previous research suggests that low n-3 long-chain polyunsaturated fatty acid ( n-3PUFA ) status is associated with higher levels of depression in clinical population s. This analysis aim ed to investigate the relationship between depressed mood and  n-3PUFA  status in a non- clinical population . The analysis was conducted on data collected as part of a large r and omized controlled trial investigating the impact of n-3PUFA supplementation on depressed mood in a community-based population . On entry into the trial , data on depressed mood were collected using the Depression , Anxiety and Stress Scales ( DASS ) and the Beck Depression Inventory ( BDI ) . Plasma concentrations of various n-3PUFAs and n-6 long-chain polyunsaturated fatty acids ( n-6PUFAs )  were obtained from fasting venous blood sample s , and various demographics were also measured . Using regression , there was no evidence of an association between either measure of depressed mood and any of the measures of n-3PUFA status or of n-6PUFA : n-3PUFA ratios . Clear associations were also not found when demographic factors were included in the analyses . These findings suggest that n-3PUFAs may not have a role in the aetiology of  minor depression . This is also consistent with the results of other studies that have not demonstrated an association between depressed mood and  n-3PUFA  status in non- clinical population s and epidemiological studies that have not demonstrated an association between depressed mood and  n-3PUFA  intake in these population BACKGROUND Inflammation plays an important role in the pathogenesis of coronary artery disease . We examined whether dietary supplementation with alpha-linolenic acid ( ALA , 18:3n-3 ) affects the levels of inflammatory markers in dyslipidaemic patients . METHODS We recruited 76 male dyslipidaemic patients ( mean age=51+/-8 years ) following a typical Greek diet . They were r and omly assigned either to 15 ml of linseed oil ( rich in ALA ) per day ( n=50 ) or to 15 ml of safflower oil ( rich in linoleic acid ( LA , 18:2n-6 ) ) per day ( n=26 ) . The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1 . Dietary intervention lasted for 3 months . Blood lipids and C-reactive protein ( CRP ) , serum amyloid A ( SAA ) , and interleukin-6 ( IL-6 ) levels were determined prior and after intervention . CRP and SAA were measured by nephelometry and IL-6 by immunoassay . RESULTS Dietary supplementation with ALA decreased significantly CRP , SAA and IL-6 levels . The median decrease of CRP was 38 % ( 1.24 vs. 0.93 mg/l , P=0.0008 ) , of SAA 23.1 % ( 3.24 vs. 2.39 mg/l , P=0.0001 ) and of IL-6 10.5 % ( 2.18 vs. 1.7 pg/ml , P=0.01 ) . The decrease of inflammatory markers was independent of lipid changes . Dietary supplementation with LA did not affect significantly CRP , SAA and IL-6 concentrations but decreased cholesterol levels . CONCLUSIONS Dietary supplementation with ALA for 3 months decreases significantly CRP , SAA and IL-6 levels  in dyslipidaemic patients . This anti-inflammatory effect may provide a possible additional mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in primary and secondary prevention of coronary artery disease BACKGROUND Depression is common in individuals with diabetes . The present study is the first r and omized controlled trial to test the efficacy of omega-3 ethyl-eicosapentaenoic acid ( E-EPA ) as adjuvant to antidepressant medication in the treatment of depression in adults with diabetes mellitus . METHODS In the VU University Medical Center , we conducted a 12-week , placebo-controlled , double-blind , parallel-group intervention study of E-EPA ( 1g/day ) versus placebo in 25 diabetes patients meeting DSM-IV criteria for major depressive disorder , who were already using antidepressant medication . The primary outcome was severity of depressive symptoms , assessed by the Montgomery Asberg Depression Rating Scale ( MADRS ) at baseline and 12-week follow-up at two-weekly intervals . Blood sample s were collected at baseline and at 12-week follow-up to determine EPA levels in erythrocyte membranes . Data were analyzed with ANOVA for repeated measures . RESULTS Thirteen participants were r and omly assigned to  E-EPA ; 12 participants were given  placebo . At 12-week follow-up , erythrocyte membranes from patients receiving E-EPA contained tripled levels of EPA , while no changes were noted in participants receiving placebo . In both groups , depressive symptoms significantly decreased over time ( F=21.14 , p<0.001 ) , yet no significant differences were found between those treated with E-EPA versus placebo ( F=1.63 , p=0.17 ) . LIMITATIONS Although having sufficient study power , this study had a relatively small sample size . Small effects could not be detected , and dose-dependent effects could not be studied . CONCLUSIONS No evidence was found for the efficacy of adding E-EPA to antidepressants in reducing depressive symptoms in diabetic patients with co-morbid depression OBJECTIVE To compare 2 omega-3 ( n-3 ) preparations enriched with eicosapentaenoic acid ( EPA ) versus docosahexaenoic acid ( DHA ) as monotherapy for major depressive disorder ( MDD ) in a 2-site , placebo-controlled , r and omized , double-blind clinical trial . METHOD 196 adults ( 53 % female ; mean [ SD ] age = 44.7 [ 13.4 ] years ) with DSM-IV MDD and a baseline 17-item Hamilton Depression Rating Scale ( HDRS-17 ) score ≥ 15 were r and omized equally from May 18 , 2006 , to June 30 , 2011 , to 8 weeks of double-blind treatment with oral EPA-enriched n-3 1000 mg/d , DHA-enriched n-3 1,000 mg/d , or placebo . RESULTS 154 subjects completed the study . Modified intent-to-treat ( mITT ) analysis ( n = 177 subjects with ≥ 1 postbaseline visit ; 59.3 % female , mean [ SD ] age 45.8 [ 12.5 ] years ) employed mixed-model repeated measures ( MMRM ) . All 3 groups demonstrated statistically significant improvement in the HDRS-17 ( primary outcome measure ) , 16-item Quick Inventory of Depressive Symptomatology-Self Report ( QIDS-SR-16 ) , and Clinical Global Improvement-Severity Scale ( CGI-S ) ( P < .05 ) , but neither n-3 preparation separated from placebo ( P > .05 ) . Response and remission rates were in the range of 40%-50 % and 30 % , respectively , for all treatments , with no significant differences between groups . One subject receiving EPA-enriched n-3 discontinued due to worsening depression , and 1 subject receiving placebo discontinued due to an unspecified " negative reaction " to pills . CONCLUSIONS Neither EPA-enriched nor DHA-enriched n-3 was superior to placebo for the treatment of MDD . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00517036 OBJECTIVE To document the short-term efficacy of omega-3 supplementation in reducing depressive symptoms in patients experiencing a major depressive episode ( MDE ) . METHOD Inclusive , double-blind , r and omized , controlled , 8-week , parallel-group trial , conducted October 17 , 2005 through January 30 , 2009 in 8 Canadian academic and psychiatric clinics . Adult out patients ( N = 432 ) with MDE ( Mini-International Neuropsychiatric Interview , version 5.0.0 , criteria ) lasting at least 4 weeks , including 40.3 % taking antidepressants at baseline , were r and omly assigned to 8 weeks of 1,050 mg/d of eicosapentaenoic acid ( EPA ) and 150 mg/d of docosahexaenoic acid ( DHA ) or matched sunflower oil placebo ( 2 % fish oil ) . The primary outcome was the self-report Inventory of Depressive Symptomatology ( IDS-SR(30 ) ) ; the secondary outcome was the clinician-rated Montgomery-Åsberg Depression Rating Scale ( MADRS ) . RESULTS The adjusted mean difference between treatment and placebo was 1.32 points ( 95 % CI , -0.20 to 2.84 ; P = .088 ) on the IDS-SR(30 ) and 0.97 points ( 95 % CI , -0.012 to 1.95 ; P = .053 ) on the MADRS . Planned subgroup analyses revealed a significant interaction of comorbid anxiety disorders and study group ( P = .035 ) . For patients without comorbid anxiety disorders ( n = 204 ) , omega-3 supplementation was superior to placebo , with an adjusted mean difference of 3.17 points on the IDS-SR(30 ) ( 95 % CI , 0.89 to 5.45 ; P = .007 ) and 1.93 points ( 95 % CI , 0.50 to 3.36 ; P = .008 ) on the MADRS . CONCLUSIONS In this heterogeneous sample of patients with MDE , there was only a trend toward superiority of omega-3 supplementation over placebo in reducing depressive symptoms . However , there was a clear benefit of omega-3 supplementation among patients with MDE without comorbid anxiety disorders . TRIAL REGISTRATION controlled-trials.com Identifier : IS RCT N47431149 BACKGROUND An ecological analysis found that the docosahexaenoic acid content in mother 's milk and seafood intake were inversely correlated with postpartum depression . This prospect i ve study investigated the relationship of consumption of selected high-fat foods and specific types of fatty acids with the risk of postpartum depression . METHOD The subjects were 865 Japanese women .  Dietary data were obtained from a self-administered diet history question naire during pregnancy . The Edinburgh Postnatal Depression Scale ( EPDS ) was used for the evaluation of postpartum depression . Adjustment was made for age , gestation , parity , cigarette smoking , family structure , family income , education , changes in diet in the previous month , season when data at baseline were collected , body mass index , time of delivery before the second survey , medical problems in pregnancy , baby 's sex and baby 's birthweight . RESULTS The percentage of women with high depression scores was 14.0 % . No evident dose-response associations were observed between intake of fish , meat , eggs , dairy products , total fat , saturated fatty acids , monounsaturated fatty acids , n-3 polyunsaturated fatty acids , n-6 polyunsaturated fatty acids , linoleic acid , alpha-linolenic acid , arachidonic acid , eicosapentaenoic acid or docosahexaenoic acid and the ratio of n-3 to n-6 polyunsaturated fatty acids and the risk of postpartum depression . However , there was an inverted J-shaped relationship between intake of n-3 polyunsaturated fatty acids and docosahexaenoic acid and the risk of postpartum depression . CONCLUSIONS This study failed to substantiate a clear inverse relationship between fish and n-3 polyunsaturated fatty acid intake and postpartum depression . Further investigations are needed to determine whether fish and n-3 polyunsaturated fatty acid consumption is preventive against postpartum depression BACKGROUND Omega-3 fatty acid ( O3FA ) levels and dimensional personality measures have been associated with major depression and the course of depressive illness . We sought to study the utility of O3FA levels and dimensional personality measures as predictors of early improvement with escitalopram . METHODS Twenty-four participants were enrolled in an open-label trial of escitalopram 10 mg/d for 4 weeks . Baseline erythrocyte O3 levels and dimensional personality assessment s were obtained . RESULTS Using a conservative , intention-to-treat analysis , baseline neuroticism ( r = -0.57 ; P = .007 ) , as measured by the Revised NEO Personality Inventory but not erythrocyte O3 levels , was correlated with improvements on escitalopram . A facet analysis of the neuroticism domain showed the relationship with antidepressant response to be focused on trait anxiety ( r = -0.65 ; P = .002 ) . CONCLUSIONS Anxiety may have important prognostic implication s on subsequent response to selective serotonin reuptake inhibitors , such as escitalopram OBJECTIVE Studies have reported that countries with high rates of fish oil consumption have low rates of depressive disorder . The authors studied a specific omega-3 fatty acid , the ethyl ester of eicosapentaenoic acid ( E-EPA ) , as an adjunct to treatment for depressive episodes occurring in patients with recurrent unipolar depressive disorder who were receiving maintenance antidepressant therapy . METHOD Twenty patients with a current diagnosis of major depressive disorder participated in a 4-week , parallel-group , double-blind addition of either placebo or E-EPA to ongoing antidepressant therapy .  Seventeen of the patients were women , and three were men . RESULTS Highly significant benefits of the addition of the omega-3 fatty acid compared with placebo were found by week 3 of treatment . CONCLUSIONS It is not possible to distinguish whether E-EPA augments antidepressant action in the manner of lithium or has independent antidepressant properties of its own BACKGROUND It has been hypothesized that depletion of cell membrane n3 polyunsaturated fatty acids ( PUFA ) , particularly docosahexanoic acid ( DHA ) , may be of etiological importance in depression . METHODS We measured the fatty acid composition of phospholipid in cell membranes from red blood cells ( RBC ) of 15 depressive patients and 15 healthy control subjects . RESULTS Depressive patients showed significant depletions of total n3 PUFA and particularly DHA . Incubation of RBC from control subjects with hydrogen peroxide abolished all significant differences between patients and controls . CONCLUSIONS These findings suggest that RBC membranes in depressive patients show evidence of oxidative damage . Possible interpretations , and implication s for the etiology and treatment of depression , are discussed OBJECTIVE Evidence from several clinical trials in patients with coronary heart disease suggests that depression that does not respond to treatment is associated with a particularly high risk of adverse cardiac outcomes . The purpose of this study was to determine whether obstructive sleep apnea/hypopnea syndrome ( OSAHS ) is associated with a poor response to  antidepressant medication  in patients with coronary heart disease . METHOD This was a secondary analysis of data from a r and omized , double-blind , placebo-controlled clinical trial of omega-3 fatty-acid augmentation of sertraline for depression in patients with coronary heart disease . Patients with documented coronary heart disease were recruited between May 2005 and December 2008 from cardiology practice s in St Louis , Missouri , and through cardiac diagnostic laboratories affiliated with Washington University School of Medicine , St Louis , Missouri . One hundred five patients ( mean age = 58 years ) with coronary heart disease and current major depressive disorder ( DSM-IV ) were r and omized to receive sertraline plus either omega-3 or placebo for 10 weeks . Cyclical heart-rate patterns associated with OSAHS were detected via ambulatory electrocardiography prior to treatment . Symptoms of depression were measured at baseline and follow-up with the Beck Depression Inventory-II ( BDI-II ) and the 17-item Hamilton Depression Rating Scale ( HDRS-17 ) . The primary endpoint was the BDI-II score at 10 weeks . RESULTS Thirty of the 105 patients ( 29 % ) were classified as having probable moderate to severe OSAHS on the basis of nighttime heart-rate patterns . These OSAHS patients had significantly higher scores on both the BDI-II ( t = -2.78 , P = .01 ) and the HDRS-17 ( t = -2.33 , P = .02 ) at follow-up as compared to the reference group . Adjustment for baseline depression score , treatment arm ( omega-3 vs placebo ) , body mass index , and inflammatory markers did not change the results . Patients with OSAHS reported higher item scores at follow-up on all depressive symptoms measured with the BDI-II compared to those without OSAHS . CONCLUSIONS Obstructive sleep apnea/hypopnea syndrome is associated with a relatively poor response to sertraline treatment for depression . Future research should determine the contribution of OSAHS to the increased risk of adverse cardiac outcome associated with treatment-resistant depression OBJECTIVE This study was an evaluation of the omega-3 fatty acid docosahexaenoic acid ( DHA ) for the treatment of major depression . METHOD Thirty-six depressed patients were r and omly assigned to receive DHA , 2 g/day , or placebo for 6 weeks . Response was defined a priori as a > or = 50 % reduction in the score on the Montgomery-Asberg Depression Rating Scale .  Thirty-five participants were evaluable ; 18 received DHA , and 17 received placebo . RESULTS Response rates were 27.8 % in the DHA group and 23.5 % in the placebo group . The difference in response rates between groups did not reach statistical significance . CONCLUSIONS This trial failed to show a significant effect of DHA monotherapy in subjects with major depression Background : Controversy over the efficacy of n-3 polyunsaturated fatty acids ( PUFAs ) in depression continues to this day . The present study investigated the hypothesis that n-3 PUFA supplementation reduces depressive symptoms in Korean patients with major depressive disorder . Methods : In a r and omized , double-blind , placebo-controlled , 12-week , parallel-group trial , 35 patients with Center for Epidemiological Studies Depression Scale Korean version ( CES-D-K ) scores ≥25 and depression confirmed by a psychiatrist were assigned to take either 3 capsules of n-3 PUFAs ( 1,140 mg of EPA + 600 mg of DHA ; n = 18 ) or placebo ( olive oil + safflower oil ; n = 17 ) . Results : Supplementation with n-3 PUFAs significantly reduced Clinical Global Impression Improvement ( CGI-I ) scores as compared with intake of placebo using intention-to-treat analysis with last-observation-carried-forward after adjusting for energy , fat , and fish intake . However , the CES-D-K , Hamilton Depression Rating Scale-17 , and Clinical Global Impression Scale scores did not significantly differ between the n-3 PUFA and placebo groups . After supplementation with n-3 PUFAs , the erythrocyte levels of n-3 PUFAs were significantly increased , but n-6 PUFA levels were decreased . Conclusions : n-3 PUFAs demonstrated an advantage over placebo that did not reach clinical significance , although CGI-I score was significantly decreased in the n-3 PUFA group as compared with the placebo group BACKGROUND Epidemiological and clinical studies suggest that increased intake of eicosapentaenoic acid ( EPA ) alleviates unipolar depression . AIMS To examine the efficacy of EPA in treating depression in bipolar disorder . METHOD In a12-week , double-blind study individuals with bipolar depression were r and omly assigned to adjunctive treatment with placebo ( n=26 ) or with 1 g/day ( n=24 ) or 2 g/day ( n=25 ) of ethyl-EPA . Primary efficacy was assessed by the Hamilton Rating Scale for Depression ( HRSD ) , with changes in the Young Mania Rating Scale and Clinical Global Impression Scale ( CGI ) as secondary outcome measures . RESULTS There was no apparent benefit of 2 g over 1 g ethyl-EPA daily . Significant improvement was noted with ethyl-EPA treatment compared with placebo in the HRSD ( P=0.04 ) and the CGI ( P=0.004 ) scores . Both doses were well tolerated . CONCLUSIONS Adjunctive ethyl-EPA is an effective and well-tolerated intervention in bipolar depression BACKGROUND The results of pilot trials suggest that omega-3 fatty acids may have efficacy in the treatment of mood symptoms in bipolar disorder . METHODS We conducted a 4-month , r and omized , placebo-controlled , adjunctive trial of ethyl-eicosapentanoate ( EPA ) 6 g/day in the treatment of bipolar depression and rapid cycling bipolar disorder . Subjects were receiving mood-stabilizing medications at therapeutic doses or plasma concentrations . The measures of efficacy were early study discontinuation , changes from baseline in depressive symptoms ( Inventory for Depressive Symptomology total score ) and in manic symptoms ( Young Mania Rating Scale total score ) , and manic exacerbations ( " switches " ) . We also measured side effects and bleeding time , a biomarker of drug action . RESULTS Overall , there were no significant differences on any outcome measure between the EPA and placebo groups . CONCLUSIONS This study did not find overall evidence of efficacy for adjunctive treatment with EPA 6 g/day in out patients with bipolar depression or rapid cycling bipolar disorder OBJECTIVE The authors hypothesized that changes in brain membrane composition result ing from omega-3 fatty acid administration in patients with bipolar disorder would result in greater membrane fluidity , as detected by reductions in T(2 ) values . METHOD Women with bipolar disorder ( N=12 ) received omega-3 fatty acids for 4 weeks . A cohort of bipolar subjects ( N=9 ) and a group without bipolar disorder ( N=12 ) did not receive omega-3 fatty acids .  T(2 ) values were acquired at baseline and after 4 weeks . RESULTS Bipolar subjects who received omega-3 fatty acids had significant decreases in T(2 ) . There was a dose-dependent effect when the bipolar omega-3 fatty acid group was subdivided into high- and low-dose cohorts . CONCLUSIONS Omega-3 fatty acids lowered T(2 ) values , consistent with the hypothesis that the fluidity of cell membranes was altered . Further studies are needed to clarify the significance of alterations in brain physiology induced by omega-3 fatty acids , as reflected in T(2 ) values OBJECTIVE To examine the efficacy and tolerability of ethyl-eicosapentaenoate ( EPA-E ) monotherapy for major depressive disorder ( MDD ) . METHOD Fifty-seven adults with DSM-IV MDD were r and omly assigned from January 2003 until June 2006 to receive 1 g/d of eicosapentaenoic acid ( EPA ) or placebo for 8 weeks in a double-blind , r and omized , controlled pilot study . Response criteria were on the basis of the 17-item Hamilton Depression Rating Scale ( HDRS-17 ) . Subjects ' plasma lipid profiles were examined by gas chromatography . RESULTS Thirty-five subjects ( 63 % female ; mean + /- SD age = 45 + /- 13 years ) were eligible for the intent-to-treat ( ITT ) analysis . In the ITT sample , mean + /- SD HDRS-17 scores decreased from 21.6 + /- 2.7 to 13.9 + /- 8.9 for the EPA group ( n = 16 ) and from 20.5 + /- 3.6 to 17.5 + /- 7.5 for the placebo group ( n = 19 ) ( P = .123 ) ; the effect size for EPA was 0.55 . ITT response rates were 38 % ( 6/16 ) for EPA , and 21 % ( 4/19 ) for placebo ( P = .45 ) . Among the 24 study completers , mean + /- SD HDRS-17 scores decreased from 21.3 + /- 3.0 to 11.1 + /- 8.1 for the EPA group and from 20.5 + /- 3.8 to 16.3 + /- 6.9 for the placebo group ( P = .087 ) ; the effect size for EPA was 0.73 . Completer response rates were 45 % ( 5/11 ) for EPA , and 23 % ( 3/13 ) for placebo ( P = .39 ) . Among EPA subjects , baseline n-6/n-3 ratio was associated with decrease in HDRS-17 score ( r = -0.686 , P = .030 ) and with treatment response ( P = .032 ) ; change in n-6/n-3 ratio was associated with change in HDRS-17 score ( r = .784 , P = .032 ) . Side effects , reported in 2 EPA subjects and 5 placebo subjects , were exclusively gastrointestinal , mild , and not associated with discontinuation . CONCLUSIONS EPA demonstrated an advantage over placebo that did not reach statistical significance , possibly due to the small sample and low completer rates , which were the major study limitations . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00096798 Converging evidence suggests that omega-3 polyunsaturated fatty acids have aetiological importance in depression . To determine the effect of adding fish oil to existing therapy in participants who were being treated for depression in a community setting , 77 participants were r and omly assigned to receive 8 g of either fish or olive oil per day in addition to their existing therapy . Fifty-nine ( 77 % ) participants completed 12 weeks of treatment . Dietary , biochemical and lifestyle factors were measured throughout the study . Mood was assessed using the Short Form Hamilton Depression Rating Scale ( HDRS-SF ) and the Beck Depression Inventory II . Sample size calculations were based on the HDRS-SF . Intention-to-treat and per protocol analyses were carried out using residual maximum likelihood . There was no evidence that fish oil improved mood when compared to the placebo oil , despite an increase in circulating omega-3 polyunsaturated fatty acids . However , mood improved significantly in both groups within the first 2 weeks of the study ( P<0.001 ) and this improvement was sustained throughout . In conclusion , fish oil was no more effective than the control as an add-on therapy for depression in this setting Dietary deficiencies in essential omega-3 polyunsaturated fatty acids derived from fish are associated with depression and some fish oils may have therapeutic benefits . We aim ed to determine whether taking tuna fish oil confers any additional benefit to conventional outpatient treatment for major depression . A r and omized double-blind placebo-controlled four-month trial comparing tuna fish oil versus placebo was conducted on 83 out patients with major depression . Despite large reductions in depression there were no significant differences at any assessment time point between patients receiving fish oil compared to placebo .  Red blood cell incorporation of fatty acids indicated good compliance with oil supplementation , although this sample was not initially deficient in omega-3s . This particular dose and type of fish oil conferred no additional benefit to conventional treatment of depression in this sample . Future studies could target participants with pre-existing omega-3 deficiency and appraise alternate enriched types and higher doses of omega-3 supplementation BACKGROUND In depressed patients , low blood levels of eicosapentaenoic acid are seen . We tested the antidepressive effect of ethyl-eicosapentaenoate in these patients . METHODS We included 70 patients with persistant depression despite ongoing treatment with an adequate dose of a st and ard antidepressant .  Patients were r and omized on a double-blind basis to placebo or ethyl-eicosapentaenoate at dosages of 1 , 2 , or 4 g/d for 12 weeks in addition to unchanged background medication . Patients underwent assessment using the 17-item Hamilton Depression Rating Scale , the Montgomery-Asberg Depression Rating Scale , and the Beck Depression Inventory . RESULTS Forty-six ( 88 % ) of 52 patients receiving ethyl-eicosapentaenoate and 14 ( 78 % ) of 18 patients receiving placebo completed the 12-week study with no serious adverse events . The 1-g/d group showed a significantly better outcome than the placebo group on all 3 rating scales . In the intention-to-treat group , 5 ( 29 % ) of 17 patients receiving placebo and 9 ( 53 % ) of 17 patients receiving 1 g/d of ethyl-eicosapentaenoate achieved a 50 % reduction on the Hamilton Depression Rating Scale score . In the per- protocol group , the corresponding figures were 3 ( 25 % ) of 12 patients for placebo and 9 ( 69 % ) of 13 patients for the 1-g/d group . The 2-g/d group showed little evidence of efficacy , whereas the 4-g/d group showed nonsignificant trends toward improvement . All of the individual items on all 3 rating scales improved with the 1-g/d dosage of ethyl-eicosapentaenoate vs placebo , with strong beneficial effects on items rating depression , anxiety , sleep , lassitude , libido , and suicidality . CONCLUSION Treatment with ethyl-eicosapentaenoate at a dosage of 1 g/d was effective in treating  depression in patients who remained depressed despite adequate st and ard therapy Background : Low brain-derived neurotrophic factor ( BDNF ) levels are observed in both depressed and diabetes patients . Animal research has shown that omega-3 polyunsaturated fatty acids increase BDNF levels . In this exploratory r and omized double-blind placebo-controlled study in diabetes patients with major depression , we tested whether ( a ) omega- 3 ethyl-eicosapentaenoic acid ( E-EPA ) leads to increased serum BDNF levels and ( b ) whether changes in BDNF levels are associated with corresponding changes in depression . Methods : Patients received 1 g/day E-EPA ( n = 13 ) or placebo ( n = 12 ) for 12 weeks , in addition to ongoing antidepressant therapy . At baseline and 12-week follow-up , we determined serum BDNF levels and depression severity , using the Montgomery-Åsberg Depression Rating Scale . Results : We found no effect of E-EPA  on BDNF levels ( t = –0.144 , p = 0.887 ) , and changes in BDNF levels and depression severity were not significantly associated ( Spearman ’s ρ = –0.115 , p = 0.593 ) . Conclusion : Our study does not provide evidence that supplementation with E-EPA  improves BDNF levels in depressed diabetes patients already using antidepressants AIM US authorities have recommended ' black-box ' warnings for antidepressants because of the increased risk of suicidality for individuals up to age 25 . There is thus a clinical and ethical imperative to provide effective treatment for  youth depression  with an acceptable risk-benefit balance . Long-chain omega-3 polyunsaturated fatty acids ( PUFAs ) play an important role in a range of physiological processes in living organisms . Supplementation with omega-3 PUFAs has been shown to have a range of beneficial effects on both physical and mental health , and results of previous trials suggest that omega-3 PUFAs may be a safe and effective treatment for depression . However , conclusions from these trials have been limited by their relatively small sample sizes . METHODS This trial will test the effectiveness of a 12-week parallel group , double-blind , r and omized , placebo-controlled trial of 1.4 g day(-1 ) omega-3 PUFAs in help seeking 15- to 25-year-olds ( N = 400 ) presenting with major depressive disorder . The primary hypothesis is that young people will show greater improvement of depressive symptoms after 12 weeks of treatment with omega-3 PUFAs plus cognitive behavioural case management compared with treatment with placebo plus cognitive behavioural case management . CONCLUSION Because of using a large sample , results from this study will provide the strongest evidence to date to inform the use of omega-3 PUFAs as first-line therapy in young people presenting with major depressive disorder . The study also heralds an important step towards indicated prevention of persistent depression , which may reduce the burden , stigmatization , disability and economic consequences of this disorder Objective : To compare therapeutic effects of eicosapentaenoic acid ( EPA ) , fluoxetine and a combination of them in major depression . Method : Sixty out patients with a diagnosis of major depressive disorder based on DSM-IV criteria and a score ≥15 in the 17-item Hamilton Depression Rating Scale ( HDRS )  were r and omly allocated to receive daily either 1000 mg EPA or 20 mg fluoxetine , or their combination for 8 weeks . Double dummy technique was used to double blind the study . Patients were assessed at 2 week intervals . Change in HDRS was the primary outcome measure . Results : Analysis of covariance for HDRS at week 8 across treatment groups was performed in 48 patients who completed at least 4 weeks of the study , with the last observation carried forward . Treatment , age of onset and baseline HDRS had a significant effect on HDRS at week 8 . EPA + fluoxetine combination was significantly better than fluoxetine or EPA alone from the fourth week of treatment . Fluoxetine and EPA appear to be equally effective in controlling depressive symptoms . Response rates ( ≥50 % decrease in baseline HDRS ) were 50 % , 56 % and 81 % in the fluoxetine , EPA and combination groups , respectively . Conclusions : In the present 8 week trial EPA and fluoxetine had equal therapeutic effects in major depressive disorder . EPA + fluoxetine combination was superior to either of them alone Objective : To compare the effects of enriched ethyl-eicosapentaenoic acid ( E-EPA ) omega-3 fatty acid supplementation with those of placebo on hot flashes ( HFs ) and quality of life among middle-aged women . Methods : Women were considered for participation if they were between 40 and 55 years of age and had moderate to severe psychological distress . A total of 120 women were r and omly assigned to E-EPA or placebo for 8 weeks . Only women with HFs were included in this analysis ( E-EPA , n = 45 ; placebo , n = 46 ) . Outcomes were changes from baseline to week 8 postintervention regarding hot flash ( HF ) frequency ( number of HFs per day ) , intensity and score ( frequency × intensity ) , and Menopause-specific Quality of Life question naire scores . Results : At baseline , the average number of HFs was 2.8 per day . After 8 weeks , HF frequency and score decreased significantly in the E-EPA group compared with the placebo group . There was no difference in the change in HF intensity between groups . Frequency of HFs declined by a mean of 1.58 per day ( 95 % CI , −2.18 to −0.98 ) in the E-EPA group and by 0.50 per day ( 95 % CI , −1.20 to 0.20 ) in the placebo group . The odds of being a responder among those taking E-EPA were about three times greater than among those taking placebo ( odds ratio , 2.70 ; 95 % CI , 1.03 - 7.03 ; P = 0.04 ) . Menopause-Specific Quality of Life scores improved significantly over time in both groups but no significant differences were noted between them . Conclusions : Supplementation with E-EPA omega-3 fatty acid  reduced HF frequency and improved the HF score relative to placebo . These results need to be confirmed by a clinical trial specifically design ed to evaluate HFs in more symptomatic women
BACKGROUND Major depressive disorder ( MDD ) is highly debilitating , difficult to treat , has a high rate of recurrence , and negatively impacts the individual and society as a whole .
One emerging potential treatment for MDD is n-3 polyunsaturated fatty acids ( n-3PUFAs ) , also known as omega-3 oils , naturally found in fatty fish , some other seafood , and some nuts and seeds .
Various lines of evidence suggest a role for n-3PUFAs in MDD , but the evidence is far from conclusive .
Investigations of heterogeneity suggest differential effects of n-3PUFAs , depending on severity of depressive symptoms , where no effects of n-3PUFAs are found in studies of individuals with mild depressive symptomology , but possible benefit may be suggested in studies of individuals with more severe depressive symptomology .
OBJECTIVES To assess the effects of n-3 polyunsaturated fatty acids ( also known as omega-3 fatty acids ) versus a comparator ( e.g. placebo , anti-depressant treatment , st and ard care , no treatment , wait-list control ) for major depressive disorder ( MDD ) in adults .