Evidence map›Paper›PMID 32909076›Full record

Trial reportPsychopharmacology2020

A phase 2a randomised, double-blind, placebo-controlled, parallel-group, add-on clinical trial of ebselen (SPI-1005) as a novel treatment for mania or hypomania.

Ann L Sharpley, Clare Williams, Adele A Holder, Beata R Godlewska, Nisha Singh, Milensu Shanyinde, Orla MacDonald, Philip J Cowen

2 registry-linked trialsOpen access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Psychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
6.7field-weighted citation impact, top 2% 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.

NCT03013400 phase2completednot on this map

A Randomised, Parallel Group, Double Blind, Placebo Controlled, Add on Clinical Trial to Investigate Whether the Lithium Mimetic, Ebselen, Can Reduce Symptoms of Hypomania and Mania in Bipolar Patients

TypeinterventionalSponsorUniversity of OxfordRan2017 to 2019Enrolled60ConditionsBipolar Disorder, Bipolar Disorder, ManicArmsEbselen, Placebo oral capsule
NCT05117710 phase1unknown statusnot on this mapstarted 2021, after this paper: background citation

Does the IMPase Inhibitor, Ebselen, Affect Emotional Processing and Brain Myo-inositol in Treatment-resistant Depression?

TypeinterventionalSponsorUniversity of OxfordRan2021 to 2024Enrolled50ConditionsDepressive Disorder, Treatment-ResistantArmsEbselen, Placebo
3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 61 citations in OpenAlex.

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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

8 authors at 3 institutions in 1 country.

Ann L SharpleyNeurosciences Building, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK.ORCID https://orcid.org/0000-0002-0623-1067
Clare WilliamsNeurosciences Building, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK.
Adele A HolderNeurosciences Building, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK.
Beata R GodlewskaNeurosciences Building, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK.ORCID https://orcid.org/0000-0002-5973-3765
Nisha SinghNeurosciences Building, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK.ORCID https://orcid.org/0000-0002-1312-688X
Milensu ShanyindeNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Orla MacDonaldOxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
Philip J CowenNeurosciences Building, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK. phil.cowen@psych.ox.ac.uk.ORCID https://orcid.org/0000-0001-5518-6138
Oxford Health NHS Foundation Trust · GBUniversity of Oxford · GBWarneford Hospital · GB

Funding

Medical Research Council MR/K022202/1Stanley Medical Research Institute 14T-005
6 · The paper itself

Abstract

rationaleLithium is an effective prophylactic and anti-manic treatment in bipolar disorder; however, its use is declining through perceived poor tolerance and toxicity. Lithium inhibits inositol monophosphatase (IMPase), a probable key therapeutic mechanism. The anti-inflammatory drug, ebselen, also inhibits IMPase and appears well-tolerated and safe.

objectivesTo assess the efficacy of adjunctive ebselen in mania using the Young Mania Rating Scale (YMRS) (primary outcome) and the Altman Self-Rating Mania (ASRM) Scale and Clinical Global Impression-Severity Scale (CGI-S) among the secondary outcomes.

methodsRandomised, double-blind, placebo-controlled, parallel-group trial conducted between October 2017 and June 2019, at Oxford Health NHS Foundation Trust. Pharmacy-controlled randomisation was computer-generated, with full allocation concealment. In/outpatients (n = 68) aged 18-70, experiencing mania or hypomania, were assigned to 3 weeks ebselen (600 mg bd) (n = 33) or placebo (n = 35). Participants received usual clinical care and psychotropic medication.

resultsEbselen was numerically, but not statistically, superior to placebo in lowering scores on the YMRS (adjusted mean difference and 95% confidence interval, - 1.71 (- 5.34 to 1.91), p = 0.35) and ASRM (- 1.36 (- 3.75 to 1.17), p = 0.29). However, scores on the CGI-S were significantly lower at week 3 in ebselen-treated participants (adjusted mean difference, - 0.58 (- 1.14 to - 0.03), p = 0.04). A post hoc analysis excluding patients taking concomitant valproate treatment magnified the difference between ebselen and placebo on the YMRS. Adverse events were comparable between groups, and mild.

conclusionsEbselen merits further investigation where concomitant psychotropic medication is better controlled and participants taking valproate are excluded. If effective, ebselen's superior tolerance and safety could make it a useful alternative to lithium.

trial registrationTrial Registry: www.clinicaltrials.gov , Identifier: NCT03013400.

Indexed as

AdultAgedAntimanic AgentsAzolesBipolar DisorderDouble-Blind MethodDrug Therapy, CombinationFemaleHumansIsoindolesMaleManiaMiddle AgedNeuroprotective AgentsOrganoselenium CompoundsTreatment OutcomeAntimanic AgentsAzolesebselenIsoindolesNeuroprotective AgentsOrganoselenium CompoundsValproic AcidAdd-onBipolarEbselenLithium mimeticManiaRandomised clinical trialYMRS

Identifiers

PMID32909076
PMCPMC7683468
OpenAlexW3084799711

What OpenQuestion holds

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LicenceCC BY
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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.