A randomized, double-blind, placebo-controlled trial of lamotrigine for prescription corticosteroid effects on the human hippocampus

Edson S Brown, Nasreen Sayed, Changho Choi, Nicholas Tustison, Jared Roberts, Michael A. Yassa, Erin A Van Enkevort, Alyson K Nakamura, Elena Ivleva, Prabha Sunderajan, David A Khan, Miguel A Vazquez, Bruce McEwen, Alexandra Kulikova, Alan B. Frol, Traci Holmes

Research output: Contribution to journalArticle

Abstract

In animals, stress and corticosteroid excess are associated with decreases in memory performance and hippocampal volume that may be prevented with agents that decrease glutamate release. Humans also demonstrate changes in memory and hippocampus with corticosteroids. In this report the effects of glutamate-release inhibitor lamotrigine on hippocampal structure and memory were examined in people receiving medically needed prescription corticosteroid therapy. A total of 54 outpatient adults (n = 28 women) receiving chronic (≥ 6 months) oral corticosteroid therapy were randomized to lamotrigine or placebo for 48 weeks. Declarative memory was assessed using the Rey Auditory Verbal Learning Test (RAVLT); structural magnetic resonance imaging (MRI) as well as single-voxel proton MR spectroscopy (1HMRS) focused on hippocampus were obtained at baseline and week 48. Utilizing a mixed-model approach, structural and biochemical data were examined by separate ANOVAs, and memory was assessed with a multi-level longitudinal model. RAVLT total scores demonstrated significantly better declarative memory performance with lamotrigine than placebo (p = 0.047). Hippocampal subfield volumes were not significantly different between the treatment groups. In summary, lamotrigine was associated with less decline in declarative memory performance than placebo in corticosteroid-treated patients. Findings suggest that, in humans as well as in animal models, glutamate release inhibitors may attenuate some of the effects on the human memory associated with corticosteroids.

LanguageEnglish (US)
JournalEuropean Neuropsychopharmacology
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Prescriptions
Hippocampus
Adrenal Cortex Hormones
Placebos
Verbal Learning
Glutamic Acid
Excitatory Amino Acid Agents
lamotrigine
Structural Models
Protons
Analysis of Variance
Outpatients
Magnetic Resonance Spectroscopy
Therapeutics
Animal Models
Magnetic Resonance Imaging

Keywords

  • Corticosteroid
  • Hippocampus
  • Magnetic resonance imaging
  • Memory
  • Prednisone

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

Cite this

A randomized, double-blind, placebo-controlled trial of lamotrigine for prescription corticosteroid effects on the human hippocampus. / Brown, Edson S; Sayed, Nasreen; Choi, Changho; Tustison, Nicholas; Roberts, Jared; Yassa, Michael A.; Van Enkevort, Erin A; Nakamura, Alyson K; Ivleva, Elena; Sunderajan, Prabha; Khan, David A; Vazquez, Miguel A; McEwen, Bruce; Kulikova, Alexandra; Frol, Alan B.; Holmes, Traci.

In: European Neuropsychopharmacology, 01.01.2019.

Research output: Contribution to journalArticle

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