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ArticleNeurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology2025

Does pre-treatment with phenobarbital prevent the acute intolerance to primidone in patients with essential tremor?

Stefano Calzetti, Lucia Zinno, Enrico Sasso, Anna Negrotti, Dario Bottignole, Emilio Perucca

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Article in Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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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

6 authors.

Stefano CalzettiNeurology Unit, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci, 14, Parma, 43126, Italy. stefano.calzetti@unipr.it.ORCID http://orcid.org/0000-0001-8793-9034
Lucia ZinnoNeurology Unit, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci, 14, Parma, 43126, Italy.ORCID http://orcid.org/0000-0002-2956-7612
Enrico SassoNeurology Unit, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci, 14, Parma, 43126, Italy.ORCID http://orcid.org/0009-0004-6919-5990
Anna NegrottiNeurology Unit, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci, 14, Parma, 43126, Italy.ORCID http://orcid.org/0000-0001-9921-230X
Dario BottignoleNeurology Unit, Azienda Ospedaliero-Universitaria of Parma, Via Gramsci, 14, Parma, 43126, Italy.
Emilio PeruccaDepartment of Medicine (Austin Hospital), The University of Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0001-8703-223X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivePrimidone (PMD) is a first-line treatment option for essential tremor (ET) but its use involves a risk of acute neurotoxic manifestations after the first dose. Our aim was to assess the prevalence of acute PMD intolerance in patients with ET and the potential protective effect of phenobarbital (PB) pre-treatment.

methodsThis retrospective study compared the frequency and severity of acute intolerance after a first dose of PMD (62.5 mg) in ET patients started on treatment without previous exposure to PB or after PB pre-treatment (10 mg/day for 2-3 weeks). Intolerance manifestations and their severity were assessed on a visual analogue scale.

resultsTwenty-five patients reported symptoms of acute intolerance to PMD, particularly somnolence, ataxia/unsteadiness, confusion, dizziness and nausea/vomiting. The prevalence of neurotoxic symptoms was 82% (23/28) among patients unexposed to PB compared with 17% (2/12) among those pre-treated with PB (p = 0.0002). Compared with no previous PB exposure, pre-treatment with PB was also associated with fewer number of adverse effects per patient (p = 0.0003) and lower severity scores (p = 0.0004). Two patients who could not tolerate PMD when administered without previous PB exposure reported no adverse effects when re-challenged after PB pre-treatment.

conclusionsPre-treatment with PB minimizes the occurrence of acute intolerance to PMD, most likely due to functional cross-tolerance. The option of receiving low-dose PB for a short period before starting on PMD should be offered to ET patients in whom PMD therapy is indicated. PB-pre-treatment should also be considered whenever occurrence of acute intolerance prevented continuation of PMD therapy.

Indexed as

AnticonvulsantsEssential TremorPhenobarbitalPrimidoneAgedAged, 80 and overFemaleHumansMaleMiddle AgedRetrospective StudiesAnticonvulsantsPhenobarbitalPrimidoneAcute intoleranceAdverse effectsCross-toleranceEssential tremorPhenobarbitalPrimidoneTreatment

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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.