Evidence map›Paper›PMID 33908296›Full record

Trial reportJournal of psychopharmacology (Oxford, England)2021

Preliminary evidence for the phosphodiesterase type-4 inhibitor, roflumilast, in ameliorating cognitive flexibility deficits in patients with schizophrenia.

Nicholas R Livingston, Peter Ct Hawkins, James Gilleen, Rong Ye, Lorena Valdearenas, Sukhi S Shergill, Mitul A Mehta

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of psychopharmacology (Oxford, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 29% of its field
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

7 citing papers in PubMed, 16 citations in OpenAlex.

  1. Trial
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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

7 authors at 3 institutions in 1 country.

Nicholas R LivingstonDepartment of Neuroimaging, King's College London, London, UK.ORCID https://orcid.org/0000-0002-6582-2545
Peter Ct HawkinsDepartment of Neuroimaging, King's College London, London, UK.ORCID https://orcid.org/0000-0002-2256-1648
James GilleenDepartment of Psychology, University of Roehampton, London, UK.
Rong YeDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Lorena ValdearenasNorth Middlesex University Hospital, Barnet, Enfield and Haringey Mental Health NHS Trust, London, UK.
Sukhi S ShergillDepartment of Psychosis Studies, King's College London, London, UK.
Mitul A MehtaDepartment of Neuroimaging, King's College London, London, UK.
King's College London · GBBarnet Enfield and Haringey Mental Health Trust · GBUniversity of Cambridge · GB

Funding

Medical Research Council G0901868Wellcome Trust
6 · The paper itself

Abstract

backgroundCognitive flexibility deficits are present in patients with schizophrenia and are strong predictors of functional outcome but, as yet, have no pharmacological treatments.

aimsThe purpose of this study was to investigate whether the phosphodiesterase type-4 inhibitor, roflumilast, can improve cognitive flexibility performance and functional brain activity in patients with schizophrenia.

methodsThis was a within-subject, randomised, double-blind, placebo-controlled, three-period crossover study using a version of the Intradimensional/Extradimensional (ID/ED) task, optimised for functional magnetic resonance imaging (fMRI), in 10 patients with schizophrenia who were scanned after receiving placebo, 100 µg or 250 µg roflumilast for 8 consecutive days. Data from an additional fMRI ID/ED study of 18 healthy participants on placebo was included to contextualise the schizophrenia-related performance and activations. The fMRI analyses included

resultsPatients on placebo demonstrated broad deficits in task performance compared to the healthy comparison group, accompanied by preserved network activity for solution search, but reduced activity in left ventrolateral prefrontal cortex (VLPFC) and posterior parietal cortex for attentional set-shifting and reduced activity in left dorsolateral prefrontal cortex (DLPFC) for reversal learning. These ROI deficits were ameliorated by 250 µg roflumilast, whereas during solution search 100 µg roflumilast reduced activity in the left orbitofrontal cortex, right DLPFC and bilateral PPC, which was associated with an improvement in formation of attentional sets.

conclusionsThe results suggest roflumilast has dose-dependent cognitive enhancing effects on the ID/ED task in patients with schizophrenia, and provides sufficient support for larger studies to test roflumilast's role in improving cognitive flexibility deficits in this clinical population.

Indexed as

AdultAgedAminopyridinesBenzamidesCognitive DysfunctionCross-Over StudiesCyclopropanesDorsolateral Prefrontal CortexDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedNeuropsychological TestsAminopyridinesBenzamidesCyclopropanesPhosphodiesterase 4 InhibitorsRoflumilastattentional set-shiftingcognitive deficitfunctional magnetic resonance imagingphosphodiesterase inhibitorSchizophrenia

Identifiers

PMID33908296
PMCPMC8435828
OpenAlexW3157931311

What OpenQuestion holds

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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 OpenQuestion graph.