Dextromethorphan (DM) is a commonly used antitussive and is currently the only FDA-approved pharmaceutical treatment for pseudobulbar affect. Its safety profile and diverse pharmacologic actions in the central nervous system have stimulated new interest for repurposing it. Numerous preclinical investigations and many open-label or blinded clinical studies have demonstrated its beneficial effects across a variety of neurological and psychiatric disorders. However, the optimal dose and safety of chronic dosing are not fully known. This review summarizes the preclinical and clinical effects of DM and its putative mechanisms of action, focusing on depression, stroke, traumatic brain injury, seizure, pain, methotrexate neurotoxicity, Parkinson's disease and autism. Moreover, we offer suggestions for future research with DM to advance the treatment for these and other neurological and psychiatric disorders.
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http://dx.doi.org/10.1016/j.pharmthera.2016.01.016 | DOI Listing |
J Prev Alzheimers Dis
February 2025
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA; School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
Background: Recent disease-modifying treatments for Alzheimer's disease show promise to slow cognitive decline, but show no efficacy towards reducing symptoms already manifested.
Objectives: To investigate the efficacy of a novel noninvasive brain stimulation technique in modulating cognitive functioning in Alzheimer's dementia (AD).
Design: Pilot, randomized, double-blind, parallel, sham-controlled study SETTING: Clinical research site at UT Southwestern Medical Center PARTICIPANTS: Twenty-five participants with clinical diagnoses of AD were enrolled from cognition specialty clinics.
Autoimmun Rev
January 2025
Department of Orthopedics, Rheumatology and Traumatology-School of Medical Sciences, University of Campinas, Brazil; Autoimmunity Lab, School of Medical Sciences, University of Campinas, Brazil. Electronic address:
Introduction: Autoimmune diseases often present in a systemic manner, affecting various organs and tissues. Involvement of the central and peripheral nervous system is not uncommon in these conditions and is associated with high morbidity and mortality. Therefore, early recognition of the neuropsychiatric manifestations associated with rheumatologic diseases is essential for the introduction of appropriate therapies with the objective of providing a better quality of life for individuals.
View Article and Find Full Text PDFLancet Neurol
February 2025
Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada; Department of Cognitive Neurology, St Joseph's Health Care London, London, ON, Canada. Electronic address:
Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.
View Article and Find Full Text PDFCell Rep
January 2025
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA; The Brain Tumor Center, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:
Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.
View Article and Find Full Text PDFJ Clin Med
January 2025
Department of Neurology, Endeavor Health, Evanston, IL 60201, USA.
: Migraine is a common neurological disorder with highly variable characteristics. While genome-wide association studies have identified genetic risk factors that implicate underlying pathways, the influence of genetic susceptibility on disease characteristics or treatment response is incompletely understood. We examined the relationships between a previously developed standardized integrative migraine polygenic genetic risk score (PRS) and migraine characteristics in a real-world, treated patient cohort.
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