title: A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia.
abstract: Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia. We examined the clinical effect of adding an omega-3 fatty acid and/or vitamins E+C to antipsychotics. It was hypothesized that lower baseline levels of polyunsaturated fatty acids (PUFAs) would predict more benefit from the add-on treatment. The trial had a multicenter, randomized, double-blind, placebo-controlled 2 × 2 factorial design. Patients aged 18-39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway. They received active or placebo ethyl-eicosapentaenoate (EPA) 2 g day⁻¹ and active or placebo vitamin E 364 mg day⁻¹+vitamin C 1000 mg day⁻¹ (vitamins) for 16 weeks. The main outcome measures were Positive and Negative Syndrome Scale (PANSS) total and subscales scores, analyzed by linear mixed models. Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects. Given separately, EPA and vitamins increased drop-out rates, whereas when combined they did not differ from placebo. In low PUFA patients, EPA alone impaired the course of total PANSS (Cohen's d=0.29; P=0.03) and psychotic symptoms (d=0.40; P=0.003), especially persecutory delusions (d=0.48; P=0.0004). Vitamins alone impaired the course of psychotic symptoms (d= 0.37; P=0.005), especially persecutory delusions (d=0.47; P=0.0005). Adding vitamins to EPA neutralized the detrimental effect on psychosis (interaction d=0.31; P=0.02). In high PUFA patients, there were no significant effects of trial drugs on PANSS scales. In conclusion, given separately during an acute episode, EPA and vitamins E+C induce psychotic symptoms in patients with low levels of PUFA. Combined, these agents seem safe.
authors.affiliation: 1] Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway [2] Division of Psychiatry, Oslo University Hospital, Aker, Oslo, Norway.
authors.forename: H
authors.initials: H
authors.lastname: Bentsen
authors.affiliation: Department of Psychosomatic Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Osnes
authors.affiliation: Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: H
authors.initials: H
authors.lastname: Refsum
authors.affiliation: Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: D K
authors.initials: DK
authors.lastname: Solberg
authors.affiliation: Nutritional Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Aker, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Bøhmer
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005231:Fatty Acids, Unsaturated / Q000097:blood; D006801:Humans; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome; D014810:Vitamin E / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D014815:Vitamins; D014810:Vitamin E; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid; D001205:Ascorbic Acid