title: Adjunctive raloxifene treatment improves attention and memory in men and women with schizophrenia.
abstract: There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study tested the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. Ninety-eight patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited into a dual-site, thirteen-week, randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene treatment in addition to their usual antipsychotic medications. Symptom severity and cognition in the domains of working memory, attention/processing speed, language and verbal memory were assessed at baseline, 6 and 13 weeks. Analyses of the initial 6-week phase of the study using a parallel groups design (with 39 patients receiving placebo and 40 receiving raloxifene) revealed that participants receiving adjunctive raloxifene treatment showed significant improvement relative to placebo in memory and attention/processing speed. There was no reduction in symptom severity with treatment compared with placebo. There were significant carryover effects, suggesting some cognitive benefits are sustained even after raloxifene withdrawal. Analysis of the 13-week crossover data revealed significant improvement with raloxifene only in attention/processing speed. This is the first study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day has beneficial effects on attention/processing speed and memory for both men and women with schizophrenia. Thus, raloxifene may be useful as an adjunctive treatment for cognitive deficits associated with schizophrenia.
authors.affiliation: 1] School of Psychiatry, University of New South Wales, Kensington, New South Wales, Australia [2] Neuroscience Research Australia, Randwick, New South Wales, Australia [3] Schizophrenia Research Institute, Darlinghurst, New South Wales, Australia.
authors.forename: T W
authors.initials: TW
authors.lastname: Weickert
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Weinberg
authors.affiliation: 1] School of Psychiatry, University of New South Wales, Kensington, New South Wales, Australia [2] Neuroscience Research Australia, Randwick, New South Wales, Australia [3] Schizophrenia Research Institute, Darlinghurst, New South Wales, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Lenroot
authors.affiliation: 1] Neuroscience Research Australia, Randwick, New South Wales, Australia [2] School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: S V
authors.initials: SV
authors.lastname: Catts
authors.affiliation: 1] School of Psychiatry, University of New South Wales, Kensington, New South Wales, Australia [2] Neuroscience Research Australia, Randwick, New South Wales, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Wells
authors.affiliation: 1] School of Psychiatry, University of New South Wales, Kensington, New South Wales, Australia [2] Neuroscience Research Australia, Randwick, New South Wales, Australia [3] Schizophrenia Research Institute, Darlinghurst, New South Wales, Australia [4] School of Psychology, Australian Catholic University, Strathfield, New South Wales, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Vercammen
authors.affiliation: School of Psychiatry, University of New South Wales, Kensington, New South Wales, Australia.
authors.forename: M
authors.initials: M
authors.lastname: O'Donnell
authors.affiliation: 1] Discipline of Psychiatry, School of Medicine, the University of Adelaide, Adelaide, South Australia, Australia [2] Northern Adelaide Local Health Network, Adelaide, South Australia, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Galletly
authors.affiliation: 1] Discipline of Psychiatry, School of Medicine, the University of Adelaide, Adelaide, South Australia, Australia [2] Northern Adelaide Local Health Network, Adelaide, South Australia, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.affiliation: 1] Discipline of Psychiatry, School of Medicine, the University of Adelaide, Adelaide, South Australia, Australia [2] School of Psychology, Flinders University, Adelaide, South Australia, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Balzan
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Short
authors.affiliation: Neuroscience Research Australia, Randwick, New South Wales, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Pellen
authors.affiliation: School of Psychiatry, University of New South Wales, Kensington, New South Wales, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Curtis
authors.affiliation: 1] School of Psychiatry, University of New South Wales, Kensington, New South Wales, Australia [2] Schizophrenia Research Institute, Darlinghurst, New South Wales, Australia.
authors.forename: V J
authors.initials: VJ
authors.lastname: Carr
authors.affiliation: Alfred Psychiatric Research Centre, Melbourne, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Kulkarni
authors.affiliation: 1] Neuroscience Research Australia, Randwick, New South Wales, Australia [2] Schizophrenia Research Institute, Darlinghurst, New South Wales, Australia [3] School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: P R
authors.initials: PR
authors.lastname: Schofield
authors.affiliation: 1] School of Psychiatry, University of New South Wales, Kensington, New South Wales, Australia [2] Neuroscience Research Australia, Randwick, New South Wales, Australia [3] Schizophrenia Research Institute, Darlinghurst, New South Wales, Australia.
authors.forename: C S
authors.initials: CS
authors.lastname: Weickert
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D001315:Australia; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008569:Memory Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D010349:Patient Compliance; D011569:Psychiatric Status Rating Scales; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D012727:Sex Characteristics; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004965:Estrogen Antagonists; D020849:Raloxifene Hydrochloride