Evidence map›Paper›PMID 30536081›Full record

Trial reportPsychopharmacology2021

An experimental medicine study of the phosphodiesterase-4 inhibitor, roflumilast, on working memory-related brain activity and episodic memory in schizophrenia patients.

James Gilleen, Yakub Farah, Cate Davison, Sarah Kerins, Lorena Valdearenas, Tolga Uz, Gez Lahu, Max Tsai, Frank Ogrinc, Avi Reichenberg and 3 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Psychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02079844 (A Randomized, Double-Blind, Placebo Controlled, 3-period, Proof of Mechanism, Cross-Over Study of Roflumilast Administered up to Steady State to Evaluate the Effects of Add-on Roflumilast to Second Generation Antipsychotics on Cognitive Impairment as Well as Brain Imaging), which is not on this map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.9field-weighted citation impact, top 14% 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.

NCT02079844 phase1completednot on this map

A Randomized, Double-Blind, Placebo Controlled, 3-period, Proof of Mechanism, Cross-Over Study of Roflumilast Administered up to Steady State to Evaluate the Effects of Add-on Roflumilast to Second Generation Antipsychotics on Cognitive Impairment as Well as Brain Imaging (ie, fMRI) and Electrical Activity (ie, EEG) Changes Observed in Subjects With Stable Schizophrenia

TypeinterventionalSponsorTakedaRan2014 to 2015Enrolled20ConditionsSchizophreniaArmsRoflumilast, Placebo, Second generation antipsychotic
3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 53 citations in OpenAlex.

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  11. Opportunities for use of neuroimaging in de-risking drug development and improving clinical outcomes in psychiatry: an industry perspective.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Review
  12. Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024
    Review
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  20. Drug Discovery and Development Targeting Dementia.Pharmaceuticals (Basel, Switzerland) · 2023
    Review
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

13 authors at 4 institutions in 2 countries.

James GilleenPsychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, SE5 8AF, UK. james.gilleen@roehampton.ac.uk.ORCID http://orcid.org/0000-0003-1095-9058
Yakub FarahPsychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, SE5 8AF, UK.
Cate DavisonDepartment of Forensic and Neurodevelopmental Science, IoPPN, Kings College London, London, SE5 8AF, UK.
Sarah KerinsPsychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, SE5 8AF, UK.
Lorena ValdearenasPsychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, SE5 8AF, UK.
Tolga UzTakeda Development Center Americas, Inc., Deerfield, IL, 60010, USA.
Gez LahuTakeda Development Center Americas, Inc., Deerfield, IL, 60010, USA.
Max TsaiEli Lilly and Company, Indianapolis, IN, 46285, USA.
Frank OgrincTakeda Development Center Americas, Inc., Deerfield, IL, 60010, USA.
Avi ReichenbergDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Steve C WilliamsDepartment of Neuroimaging, IoPPN, Kings College London, London, SE5 8AF, UK.
Mitul A MehtaDepartment of Neuroimaging, IoPPN, Kings College London, London, SE5 8AF, UK.
Sukhi S ShergillPsychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, SE5 8AF, UK.
King's College London · GBDeerfield (United States) · USEli Lilly (United States) · USIcahn School of Medicine at Mount Sinai · US

Funding

Medical Research Council G0901868Takeda Pharmaceuticals U.S.A. (US) n/aWellcome Trust
6 · The paper itself

Abstract

rationaleSchizophrenia is associated with impairments in cognitive functioning yet there are no approved drugs to treat these deficits.

objectivesBased on animal models, we investigated the potential for roflumilast, a selective inhibitor of phosphodiesterase type 4 (PDE4), to improve cognition, which may act by increasing intracellular cyclic adenosine monophosphate in brain regions underlying cognitive deficits in schizophrenia.

methodsThis study consisted of a randomised, double-blind, placebo-controlled, crossover design involving 15 schizophrenia patients. In 3 treatment periods, patients were given 8 days of placebo or one of the two doses of roflumilast (100 and 250 μg daily) with 14 days of washout between treatments. The primary endpoints were dorsolateral prefrontal cortex (DLPFC) activation during a visuospatial working memory task measured with fMRI on dosing day 8 and verbal memory and working memory performance change from baseline to day 8. Least square mean change scores were calculated for behavioural outcomes; fMRI data were analysed in SPM12 with bilateral DLPFC as regions of interest.

resultsVerbal memory was significantly improved under 250 μg roflumilast (effect size (ES) = 0.77) compared to placebo. fMRI analyses revealed that increasing dose of roflumilast was associated with reduction of bilateral DLPFC activation during working memory compared to placebo, although this was not statistically significant (ES = 0.31 for the higher dose). Working memory was not improved (ES = 0.03).

conclusionsResults support the mechanistic validation of potential novel strategies for improving cognitive dysfunction in schizophrenia and suggest that PDE4 inhibition may be beneficial for cognitive dysfunction in schizophrenia.

trial registrationNCT02079844 .

Indexed as

AdultAminopyridinesAnimalsBenzamidesBrainCognitionCognition DisordersCross-Over StudiesCyclopropanesDouble-Blind MethodFemaleHumansMaleMemory, EpisodicMemory, Short-TermMiddle AgedAminopyridinesBenzamidesCyclopropanesPhosphodiesterase 4 InhibitorsRoflumilastCIASCognition‘Cognitive enhancement’fMRIMemoryPDE4‘PDE4 inhibition’RoflumilastSchizophrenia

Identifiers

PMID30536081
PMCPMC8062361
OpenAlexW2903872963

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.