1. A randomized, double-blind, placebo-controlled trial of lamotrigine for prescription corticosteroid effects on the human hippocampus
- Author
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Brown, E Sherwood, Sayed, Nasreen, Choi, Changho, Tustison, Nicholas, Roberts, Jared, Yassa, Michael A, Van Enkevort, Erin, Nakamura, Alyson, Ivleva, Elena I, Sunderajan, Prabha, Khan, David A, Vazquez, Miguel, McEwen, Bruce, Kulikova, Alexandra, Frol, Alan B, and Holmes, Traci
- Subjects
Biological Psychology ,Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Psychology ,Biomedical Imaging ,Mental Health ,Clinical Trials and Supportive Activities ,Neurosciences ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Mental health ,Adolescent ,Adrenal Cortex Hormones ,Adult ,Aged ,Antipsychotic Agents ,Double-Blind Method ,Female ,Functional Laterality ,Glutamic Acid ,Hippocampus ,Humans ,Lamotrigine ,Magnetic Resonance Imaging ,Magnetic Resonance Spectroscopy ,Male ,Memory Disorders ,Middle Aged ,Young Adult ,Memory ,Corticosteroid ,Prednisone ,Magnetic resonance imaging ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry ,Biological psychology - 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.
- Published
- 2019