Back to Search
Start Over
Effects of the antidepressant medication duloxetine on brain metabolites in persistent depressive disorder: A randomized, controlled trial
- Source :
- PLoS ONE, Vol 14, Iss 7, p e0219679 (2019), PLoS ONE
- Publication Year :
- 2019
- Publisher :
- Public Library of Science (PLoS), 2019.
-
Abstract
- BackgroundTo assess whether patients with Persistent Depressive Disorder (PDD) have abnormal levels of N-acetyl-aspartate (NAA) and whether those levels normalize following treatment with the antidepressant medication duloxetine. Furthermore, we conducted post hoc analyses of other important brain metabolites to understand better the cellular and physiological determinants for changes in NAA levels.MethodsWe acquired proton (1H) magnetic resonance spectroscopic imaging (MRSI) data on a 3 Tesla (3T), GE Magnetic Resonance Imaging (MRI) scanner in 41 patients (39.9±10.4 years, 22 males) with PDD at two time points: before the start and at the end of a 10-week, placebo-controlled, double-blind, randomized controlled trial (RCT) of the antidepressant medication duloxetine. Patients were randomized such that 21 patients received the active medication and 20 patients received placebo during the 10 week period of the trial. In addition, we acquire 1H MRSI data once in 29 healthy controls (37.7±11.2 years, 17 males).FindingsPatients had significantly higher baseline concentrations of NAA across white matter (WM) pathways and subcortical gray matter, and in direct proportion to the severity of depressive symptoms. NAA concentrations declined in duloxetine-treated patients over the duration of the trial in the direction toward healthy values, whereas concentrations increased in placebo-treated patients, deviating even further away from healthy values. Changes in NAA concentration did not mediate medication effects on reducing symptom severity, however; instead, changes in symptom severity partially mediated the effects of medication on NAA concentration, especially in the caudate and putamen.InterpretationThese findings, taken together, suggest that PDD is not a direct consequence of elevated NAA concentrations, but that a more fundamental pathophysiological process likely causes PDD and determines the severity of its symptoms. The findings also suggest that although duloxetine normalized NAA concentrations in patients, it did so by modulating the severity of depressive symptoms. Medication presumably reduced depressive symptoms through other, as yet unidentified, brain processes.Trial registrationClinicalTrials.gov NCT00360724.
- Subjects :
- Male
Central Nervous System
Magnetic Resonance Spectroscopy
Biochemistry
Nervous System
Brain mapping
Diagnostic Radiology
law.invention
chemistry.chemical_compound
0302 clinical medicine
Drug Metabolism
Randomized controlled trial
law
Metabolites
Medicine and Health Sciences
Depression (differential diagnoses)
Brain Mapping
Multidisciplinary
medicine.diagnostic_test
Depression
Radiology and Imaging
Brain
Magnetic resonance spectroscopic imaging
Middle Aged
Magnetic Resonance Imaging
Antidepressive Agents
Treatment Outcome
Data Acquisition
medicine.anatomical_structure
Medicine
Female
Anatomy
Research Article
Adult
Computer and Information Sciences
medicine.medical_specialty
Imaging Techniques
Science
Duloxetine Hydrochloride
Research and Analysis Methods
Placebo
White matter
03 medical and health sciences
Double-Blind Method
Diagnostic Medicine
Internal medicine
Mental Health and Psychiatry
mental disorders
medicine
Humans
Duloxetine
Pharmacokinetics
Pharmacology
Aspartic Acid
Depressive Disorder, Major
Mood Disorders
business.industry
Biology and Life Sciences
Magnetic resonance imaging
030227 psychiatry
Metabolism
nervous system
chemistry
business
030217 neurology & neurosurgery
Neuroscience
Subjects
Details
- ISSN :
- 19326203 and 00360724
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....096b5b878a5e26bb914d69b8f94d270f