Evidence map›Paper›PMID 28833962›Full record

Trial reportBipolar disorders2017

Biochemical and genetic predictors and correlates of response to lamotrigine and folic acid in bipolar depression: Analysis of the CEQUEL clinical trial.

E M Tunbridge, M J Attenburrow, A Gardiner, J M Rendell, C Hinds, G M Goodwin, P J Harrison, J R Geddes

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

Trial report in Bipolar disorders, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 23% 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

5 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
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 2 institutions in 1 country.

E M TunbridgeDepartment of Psychiatry, University of Oxford, Oxford, UK.ORCID 0000-0002-2966-2281
M J AttenburrowDepartment of Psychiatry, University of Oxford, Oxford, UK.
A GardinerNIHR CLAHRC Oxford, Oxford Health NHS Foundation Trust, Oxford, UK.
J M RendellDepartment of Psychiatry, University of Oxford, Oxford, UK.
C HindsOxford University Big Data Institute, University of Oxford, Oxford, UK.
G M GoodwinDepartment of Psychiatry, University of Oxford, Oxford, UK.
P J HarrisonDepartment of Psychiatry, University of Oxford, Oxford, UK.
J R GeddesDepartment of Psychiatry, University of Oxford, Oxford, UK.
Oxford Health NHS Foundation Trust · GBOpen Data Institute · GB

Funding

Medical Research CouncilWellcome Trust
6 · The paper itself

Abstract

objectivesCEQUEL (Comparative Evaluation of QUEtiapine plus Lamotrigine combination versus quetiapine monotherapy [and folic acid versus placebo] in bipolar depression) was a double-blind, randomized, placebo-controlled, parallel group, 2×2 factorial trial that examined the effect of adding lamotrigine and/or folic acid (FA) to quetiapine in bipolar depression. Lamotrigine improved depression, but its effectiveness was reduced by FA. We investigated the baseline predictors and correlates of clinical response, and the possible basis of the interaction.

methodsThe main outcome was change in depressive symptoms at 12 weeks, measured using the Quick Inventory for Depressive Symptoms-self report version 16 (QIDS-SR16). We examined the relationship between symptoms and lamotrigine levels, and biochemical measures of one-carbon metabolism and functional polymorphisms in catechol-O-methyltransferase (COMT), methylene tetrahydrofolate reductase (MTHFR) and folate hydrolase 1 (FOLH1).

resultsLamotrigine levels were unaffected by FA and did not differ between those participants who achieved remission and those with persisting symptoms. When participants with subtherapeutic serum levels were excluded, there was a main effect of lamotrigine on the main outcome, although this remained limited to those randomized to FA placebo. None of the biochemical measures correlated with clinical outcome. The negative impact of FA on lamotrigine response was limited to COMT Met carriers. FOLH1 and MTHFR had no effect.

conclusionsOur results clarify that FA's inhibition of lamotrigine's efficacy is not a pharmacokinetic effect, and that low serum lamotrigine levels contributed to lamotrigine's lack of a main effect at 12 weeks. We were unable to explain the lamotrigine-FA interaction, but our finding that it is modulated by the COMT genotype provides a starting point for follow-on neurobiological investigations. More broadly, our results highlight the value of including biochemical and genetic indices in randomized clinical trials.

Indexed as

Bipolar DisorderFolic AcidQuetiapine FumarateTriazinesAdultBrief Psychiatric Rating ScaleCatechol O-MethyltransferaseDouble-Blind MethodDrug CombinationsFemaleHumansLamotrigineMalePharmacogenomic TestingPsychotropic DrugsTreatment OutcomeCatechol O-MethyltransferaseCOMT protein, humanDrug CombinationsFolic AcidLamotriginePsychotropic DrugsQuetiapine FumarateTriazinesbipolar disordercatechol-O-methyltransferasefolatefolate hydrolaseglutathionehomocysteinemethylene tetrahydrofolate reductase

Identifiers

PMID28833962
PMCPMC5697684
OpenAlexW2746012647

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.