Brain Kinetics of Paroxetine and Fluoxetine on the Third Day of Placebo Substitution: A Fluorine MRS Study
Abstract
OBJECTIVE: This study tested whether a relationship exists between concentration and response following discontinuation of selective serotonin reuptake inhibitors. METHOD: Eight patients with remitted major depression who were taking 20 mg/day of either fluoxetine or paroxetine underwent placebo substitution for 3 days. Serum drug and brain fluorine levels were obtained before and after placebo substitution. RESULTS: With placebo substitution, a mean of 88% (SD=13%) of brain fluorine signal from fluoxetine (plus fluorinated metabolites) remained, compared with a mean of 38% (SD=17%) of the brain fluorine signal from paroxetine (plus fluorinated metabolites). Among patients taking paroxetine, adverse events during placebo substitution correlated highly with steady-state brain drug levels. CONCLUSIONS: The correlation of clinical effects with brain drug levels in the paroxetine group suggests that relationships between drug response and brain drug concentrations merit further investigation.
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- Authors
- Henry, M. E., Moore, C. M., Kaufman, M. J., Michelson, D., Schmidt, M. E., Stoddard, E., Vuckevic, A. J., Berreira, P. J., Cohen, B. M., & Renshaw, P. F.
- Affiliations
- McLean Hospital (US)
- Harvard University (US)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2000-09-01
- Volume
- 157
- Issue
- 9
- Pages
- 1506-1508
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2061815699
- Cited by
- 61
- References
- 0
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 1 · 2022: 3 · 2021: 3 · 2019: 3 · 2018: 1 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (DA-09448, R01DA009448)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- paroxetine, fluoxetine, selective serotonin reuptake inhibitors, brain drug levels, drug response, adverse drug reactions, drug metabolites
- MeSH terms
- Adult, Brain, Brain Chemistry, Depressive Disorder, Double-Blind Method, Female, Fluorine, Fluoxetine, Humans, Male, Magnetic Resonance Spectroscopy, Placebos, Selective Serotonin Reuptake Inhibitors, Paroxetine
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