title: A randomized, double-blind, placebo-controlled, crossover trial evaluating the effect of intranasal insulin on cognition and mood in individuals with treatment-resistant major depressive disorder.
abstract: Cognitive dysfunction in major depressive disorder (MDD) is identified as a primary therapeutic target; no current treatment is approved for the treatment of cognitive dysfunction in MDD. We examined whether intranasal insulin offered a beneficial effect across measures of cognitive function in adults with MDD.
  
  
  
  Thirty-five adults (18-65 years of age: 47.09±9.89) meeting criteria for a major depressive episode as per the Diagnostic and Statistical Manual (DSM)-IV-Treatment Revised were included in this randomized, double blind, placebo-controlled, crossover design study. Subjects were not stratified based on baseline cognitive deficit. Subjects were randomized to 4 weeks of either intranasal insulin 40 International Units (IU) taken four times a day (i.e., morning, afternoon, evening, and before bed) (QID) (n=19) or placebo (n=16).
  
  
  
  No between group differences were observed in change from baseline on total Montgomery Åsberg Depression Rating Scale (MADRS) score (25.98±2.81), in either of the Positive or Negative subscales of the Positive and Negative Affect Schedule (PANAS), or on a global index of neurocognition. The possibility of practice and/or carry over effect could not be excluded. Methodological refinement (e.g., stratification of subjects based on baseline cognitive deficit) may have augmented assay sensitivity.
  
  
  
  Intranasal insulin did not demonstrate statistically significant improvements on overall mood, aspects of emotional processing, neurocognitive function, or self-reported quality of life patient reported outcomes.
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Cha
authors.affiliation: Cognitive and Psychotic Disorders Lab, Department of Psychology, Queen's University, Kingston, ON, Canada.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Best
authors.affiliation: Director of Clinical Training, Department of Psychology, Queen's University, Kingston, ON, Canada; Clinician Scientist, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Bowie
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
authors.forename: Laura Ashley
authors.initials: LA
authors.lastname: Gallaugher
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
authors.forename: Hanna O
authors.initials: HO
authors.lastname: Woldeyohannes
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Joanna K
authors.initials: JK
authors.lastname: Soczynska
authors.affiliation: Department of Endocrinology, Toronto General Hospital, University Health Network, Toronto, ON, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Lewis
authors.affiliation: Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Glenda
authors.initials: G
authors.lastname: MacQueen
authors.affiliation: London Imperial Affiliated Professor, University of Cambridge, United Kingdom.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Sahakian
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Sidney H
authors.initials: SH
authors.lastname: Kennedy
authors.affiliation: Pharmacist, Investigational Pharmacy Services, University Health Network, Toronto Western Hospital, Toronto, ON, Canada.
authors.forename: Jane P
authors.initials: JP
authors.lastname: Lui
authors.affiliation: Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), Brazil.
authors.forename: Rodrigo B
authors.initials: RB
authors.lastname: Mansur
authors.affiliation: Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. Electronic address: roger.mcintyre@uhn.on.ca.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects*; D000368:Aged; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000523:psychology; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D061218:Depressive Disorder, Treatment-Resistant / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011788:Quality of Life; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007328:Insulin
keywords: Cognition; Cognitive; Cognitive dysfunction; Cognitive impairment; Emotional processing; Intranasal insulin; Major depressive disorder