Evidence mapPaperPMID 40400441Full record

Trial reportPsychological medicine2025

Effects of 28-day simvastatin administration on emotional processing, reward learning, working memory, and salivary cortisol in healthy participants at-risk for depression: OxSTEP, an online experimental medicine trial.

Riccardo De Giorgi, Shona Waters, Amy L Gillespie, Alice M G Quinton, Michael J Colwell, Susannah E Murphy, Philip J Cowen, Catherine J Harmer

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Psychological medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Riccardo De GiorgiDepartment of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.ORCID 0000-0001-5984-8696
Shona WatersDepartment of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.ORCID 0000-0002-7554-0090
Amy L GillespieDepartment of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.ORCID 0000-0003-4640-699X
Alice M G QuintonSocial, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0001-5563-4893
Michael J ColwellDepartment of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.ORCID 0000-0001-7846-2879
Susannah E MurphyDepartment of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.ORCID 0000-0001-8995-2099
Philip J CowenDepartment of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.ORCID 0000-0001-5518-6138
Catherine J HarmerDepartment of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.ORCID 0000-0002-1609-8335

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundStatins are among the most prescribed medications worldwide. Both beneficial (e.g. antidepressant and pro-cognitive) and adverse (e.g. depressogenic and cognitive-impairing) mental health outcomes have been described in clinical studies. The underlying neuropsychological mechanisms, whether positive or negative, are, however, not established. Clarifying such activities has implications for the safe prescribing and repurposing potential of these drugs, especially in people with depression.

methodsIn this double-blind, randomized, placebo-controlled experimental medicine study, we investigated the effects of simvastatin on emotional processing, reward learning, working memory, and waking salivary cortisol (WSC) in 101 people at-risk for depression due to reported high loneliness scores (mean 7.3 ± 1.2 on the UCLA scale). This trial was largely conducted during periods of social distancing due to the COVID-19 pandemic (July 2021-February 2023), and we employed a fully remote design within a UK-wide sample.

resultsHigh retention rates, minimal outlier data, and typical main effects of task condition (e.g. emotion) were seen in all cognitive tasks, indicating this approach was comparable to in-person testing. After 28 days, we found no statistically significant differences (F's < 3.0, p's > 0.20) for any of the measures of emotional processing, reward learning, working memory, and WSC.

conclusionsStudy results do not substantiate concerns regarding adverse neuropsychiatric events due to statins and support the safety of their prescribing in at-risk populations. Although other unmeasured cognitive processes may be involved, our null findings are also in line with more recent clinical evidence suggesting statins do not show antidepressant or pro-cognitive efficacy.

Indexed as

DepressionEmotionsHydrocortisoneHydroxymethylglutaryl-CoA Reductase InhibitorsLearningMemory, Short-TermRewardSimvastatinAdultCOVID-19Double-Blind MethodFemaleHealthy VolunteersHumansMaleMiddle AgedHydrocortisoneHydroxymethylglutaryl-CoA Reductase InhibitorsSimvastatinat-risk for depressionemotional processinglonelinessonline experimental medicine studyreward learningsimvastatinwaking salivary cortisolworking memory

Identifiers

PMID40400441
PMCPMC12115272

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.