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

J Affect Disord. 2017 Mar 1:210:57-65. doi: 10.1016/j.jad.2016.12.006. Epub 2016 Dec 18.

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords: Cognition; Cognitive; Cognitive dysfunction; Cognitive impairment; Emotional processing; Intranasal insulin; Major depressive disorder.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Intranasal
  • Adolescent
  • Adult
  • Affect / drug effects*
  • Aged
  • Cognition / drug effects*
  • Cognition Disorders / drug therapy
  • Cognition Disorders / etiology
  • Cognition Disorders / psychology
  • Cross-Over Studies
  • Depressive Disorder, Major / complications
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Depressive Disorder, Treatment-Resistant / complications
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Depressive Disorder, Treatment-Resistant / psychology
  • Diagnostic and Statistical Manual of Mental Disorders
  • Double-Blind Method
  • Female
  • Humans
  • Insulin / administration & dosage*
  • Insulin / therapeutic use*
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Quality of Life
  • Treatment Outcome
  • Young Adult

Substances

  • Insulin