Omega-3 fatty acids have shown promise as an adjunctive treatment for schizophrenia. However, efficacy across studies has been inconsistent. We conducted a meta-analysis of published controlled studies with the goal of detecting different efficacy profiles at various stages of schizophrenia.
Methods
An online search was conducted for randomized, double-blind, placebo-controlled clinical trials, and a meta-analysis was conducted.
Results
Ten studies met the criteria for inclusion. Among patients in the prodromal phase of schizophrenia, omega-3 supplementation reduced psychotic symptom severity and lowered conversion rates to first-episode psychosis. In patients with first-episode schizophrenia, omega-3 decreased nonpsychotic symptoms, required lower antipsychotic medication dosages, and improved early treatment response rates. Omega-3 had mixed results in patients with stable chronic schizophrenia, with only some patients experiencing significant benefits. Among patients with chronic schizophrenia, use of omega-3 fatty acids both by those experiencing acute exacerbations and those who had discontinued antipsychotic medications resulted in worsening of psychotic symptoms.
Conclusions
The data suggest that omega-3 fatty acids may be efficacious in reducing clinical symptoms for patients in the earlier stages of schizophrenia (prodrome and first episode), while producing mixed results for patients in the chronic stages. Based on these results, omega-3 fatty acids would not be recommended for acute exacerbations in patients with chronic schizophrenia nor for relapse prevention after discontinuation of antipsychotics.
Get full access to this article
View all access options for this article.
References
1.
ChewLJ, Fusar-PoliP, SchmitzT.Oligodendroglial alteration and the role of microglia in white matter injury: relevance to schizophrenia. Dev Neurosci. 2013;35:102–129.
2.
MullerN, SchwarzM.Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission. Neurotox Res. 2006;10:131–148.
3.
MüllerN, DursunSM.Schizophrenia genes, epigenetics and psychoneuroimmunology therapeutics: all make sense now?J Psychopharmacol. 2011;25:713–714.
4.
SommerIE, de WitteL, BegemannM, . Nonsteroidal anti-inflammatory drugs in schizophrenia: ready for practice or a good start? A meta-analysis. J Clin Psychiatry. 2012;73:414–419.
5.
TynanRJ, WeidenhoferJ, HinwoodM, . A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia. Brain Behav Immun. 2012;26:469–479.
6.
HuX, ZhouH, ZhangD, . Clozapine protects dopaminergic neurons from inflammation-induced damage by inhibiting microglial overactivation. J Neuroimmune Pharmacol. 2012;7:187–201.
7.
NasrallahHA.Beyond dopamine: the “other” effects of antipsychotics. Current Psychiatry. 2013;13:8–9.
8.
XimenesJC, de Oliveira GoncalvesD, SiqueiraRM, . Valproic acid: an anticonvulsant drug with potent antinociceptive and anti-inflammatory properties. Naunyn Schmiedebergs Arch Pharmacol. 2013;386:575–587.
9.
GattazWF, HübnerCK, NevalainenTJ, . Increased serum phospholipase A2 activity in schizophrenia: a replication study. Biol Psychiatry. 1990;28:495–501.
10.
McEvoyJ, BaillieRA, ZhuH, . Lipidomics reveals early metabolic changes in patients with schizophrenia: effects of atypical antipsychotics. PLo S One. 2013;8:(7)e68717.
11.
YaoJK, LeonardS, ReddyRD.Membrane phospholipid abnormalities in postmortem brains from schizophrenic patients. Schizophr Res. 2000;42:7–17.
12.
FarooquiAA, OngWY, HorrocksLA.Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol Rev. 2006;58:591–620.
13.
SimopoulousA P.Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002;21:495–505.
14.
AarvindakshanM, SitasawadS, DebsikdarV, . Essential polyunsaturated fatty acid and lipid peroxide levels in never-medicated and medicated schizophrenic patients. Biol Psychiatry. 2003;53:56–64.
15.
AssiesJ, LieverseR, VrekenP, . Significantly reduced docosahexaenoic acid concentrations in erythrocyte membranes from schizophrenic patients compared with a carefully matched control group. Biol Psychiatry. 2001;49:510–522.
16.
KhanMM, EvansDR, GunnaV, . Reduced erythrocyte membrane essential fatty acids and increased lipid peroxides in schizophrenia at the never-medicated first episode of psychosis and after years of treatment with antipsychotics. Schizophr Res. 2002;58:1–10.
17.
PeetM, LaugharneJD, MellorJ, . Essential fatty acid deficiency in erythrocyte membranes from chronic schizophrenia patients, and the clinical effects of dietary supplementation. Prostaglandins Leukot Essent Fatty Acids. 1996;55:71–75.
18.
McGorryP, HickieIB, YungAR, . Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions. Aust NZJ Psychiatry. 2006;40:616–622.
19.
MoherD, LiberatiA, TetzlaffJ, ; PRISMA Group. Preferred Reporting Items for Systematic reviews and Meta-Analyses: the PRISMA statement. J Clin Epidemiol. 2009;62:1006–1012.
20.
YungAR, PhillipsLJ, McGorryPD, . Prediction of psychosis: a step towards indicated prevention of schizophrenia. Br J Psychiatry Suppl. 1998;172:14–20.
PeetM, BrindJ, RamchandCN, . Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Schizophr Res. 2001;49:243–251.
23.
FentonWS, DickersonF, BoronowJ, . A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry. 2001;158:2071–2074.
24.
EmsleyR, MyburghC, OosthuizenP, . Randomized, placebo-controlled study of ethyl-eicosapentaenoic acid as supplemental treatment in schizophrenia. Am J Psychiatry. 2002;159:1596–1598.
25.
EmsleyR, NiehausDJ, KoenL, . The effects of eicosapentaenoic acid in tardive dyskinesia: a randomized, placebo-controlled trial. Schizophr Res. 2006;84:112–120.
26.
JamilianH, SolhiH, Jamilian RandomizedM., placebo-controlled clinical trial of omega-3 as supplemental treatment in schizophrenia. Glob J Health Sci.2014;6:103–108.
27.
PeetM, HorrobinDF; E-Multicentre E Study Group. A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms. J Psychiatr Res. 2002;36:7–18.
28.
EmsleyR, NiehausDJ, OosthuizenPP, . Safety of the omega-3 fatty acid, eicosapentaenoic acid (EPA) in psychiatric patients: results from a randomized, placebo-controlled trial. Psychiatry Res. 2008;161:284–291.
29.
van RensburgSJ, SmutsCM, HonD, . Changes in erythrocyte membrane fatty acids during a clinical trial of eicosapentaenoic acid (EPA) supplementation in schizophrenia. Metab Brain Dis. 2009;24:659–672.
30.
EmsleyR, ChilizaB, AsmalL, . A randomized, controlled trial of omega-3 fatty acids plus an antioxidant for relapse prevention after antipsychotic discontinuation in first-episode schizophrenia. Schizophr Res. 2014;158:230–235.
31.
BentsenH, OsnesK, RefsumH, . A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia. Transl Psychiatry. 2013;3:e335. doi:10.1038/tp.2013.110.
32.
BergerGE, ProffittTM, McConchieM, . Ethyleicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial. J Clin Psychiatry. 2007;68:1867–1875.
33.
AmmingerGP, SchäferMR, PapageorgiouK, . Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010;67:146–154.
PantelisC, McGorryPD, WoodSJ, . Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet. 2003;361:281–288.
36.
MeisenzahlEM, KoutsoulerisN, BottlenderR, . Structural brain alterations at different stages of schizophrenia: a voxel-based morphometric study. Schizophr Res. 2008;104:44–60.
