The effect of selective serotonin reuptake inhibitors in healthy subjects revisited: A systematic review of the literature.
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are the first-line drugs in the treatment of depression. Investigations of the effects of SSRIs in healthy individuals is a useful model to understand the mechanisms of SSRI action and potentially the underlying pathophysiology of depression. We conducted an updated systematic review of all randomized multiple-dose, placebo-controlled trials on the effect of intervention with SSRI for ≥ 7 days in healthy nonpsychiatric subjects. Tables were drawn for characteristics of the trial, quality assessment, outcome measures, and the effect of intervention with SSRI. The search strategy identified a total of 51 placebo-controlled randomized trials investigating seven different SSRIs and 249 different outcome measures. Among trials, using the same outcome measure, most associations were either contradictory or statistically nonsignificant. Replication of statistically significant findings in two or more trials showed that SSRIs compared with placebo decreased divided attention, sustained attention network, negative affects, hostility, sleep quality, and platelet 5-HT content and further increased activity in the amygdala in relation to happy faces. Factors such as age, gender, family history of psychiatric disorder, and drug level influenced the findings but were rarely systematically investigated. The newly published retrieved trials fulfilled more criteria according to the CONSORT statement. This systematic review points to effects of SSRIs increasing positive emotional processing and decreasing divided and sustained attention besides physiological effects decreasing sleep quality and platelet 5-HT content in healthy subjects. Larger studies with a translational medicines approach with improved methodology are needed on the effects of SSRIs in healthy subjects. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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A recent systematic review of healthy individuals found evidence for worsening of divided and sustained attention with SSRI treatment.
“A recent systematic review of healthy individuals even found evidence for worsening of divided and sustained attention with SSRI treatment102.”
From Paying attention to attention in depression (2019) · cites this paper as [102]
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Paying attention to attention in depression
Keller, A. S., Leikauf, J. E., Holt-Gosselin, B., Staveland, B. R., & Williams, L. M. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0616-1 · Cited by 329 · see citing works
- Authors
- Knorr, U., Madsen, J. M., & Kessing, L. V.
- Venue
- Experimental and Clinical Psychopharmacology
- Published
- 2019-10
- Volume
- 27
- Issue
- 5
- Pages
- 413-432
- ISSN
- 1064-1297 (ISSN-L)
- 1936-2293
- OpenAlex
- W2922164744
- Semantic Scholar
- ed82f5b3d0f3c690ef6c08ff2111ba381fe63642
- Cited by
- 25
- References
- 95
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 2 · 2020: 4 · 2019: 1
- FWCI
- 0.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental and Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- selective serotonin reuptake inhibitors, healthy volunteers, divided attention, sustained attention, negative affect, hostility, sleep quality, platelet serotonin, amygdala activity, depression pathophysiology, translational medicine
- MeSH terms
- Emotions, Humans, Research Design, Sleep, Randomized Controlled Trials as Topic, Outcome Assessment, Health Care, Selective Serotonin Reuptake Inhibitors, Healthy Volunteers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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