Evidence mapPaperPMID 41555041Full record

SynthesisCNS drugs2026

Clinical Presentations and Treatment of Baclofen Toxicity and Withdrawal: A Systematic Review.

Minahil Iqbal, Parth Modi, Kush Sehgal, Gabriel P A Costa, Gargi Bhattacharya, Neil Nero, Junaid H Siddiqui, Jeremy Weleff, Akhil Anand

Abstract readSystematic Review
PubMed Publisher
In one paragraph

Synthesis in CNS drugs, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing 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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Minahil IqbalAllama Iqbal Medical College, Lahore, Pakistan.ORCID 0000-0002-9320-1228
Parth ModiMedical College Baroda, Vadodara, Gujarat, India.ORCID 0009-0009-1550-3480
Kush SehgalTeerthanker Mahaveer University, Moradabad, Uttar Pradesh, India.ORCID 0009-0002-0308-3481
Gabriel P A CostaDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.ORCID 0009-0007-8702-5436
Gargi BhattacharyaDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Neil NeroFloyd D. Loop Alumni Library, Cleveland Clinic, Cleveland, OH, USA.ORCID 0000-0002-8391-4785
Junaid H SiddiquiDepartment of Neurology, Cleveland Clinic, Cleveland, OH, USA.
Jeremy WeleffDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Akhil AnandDepartment of Psychiatry and Psychology, Cleveland Clinic Center for Behavioral Health, 1730 West 25th Street/2A, Cleveland, OH, 44113, USA. akhil_anand@rogers.com.ORCID 0000-0003-4132-2690

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBaclofen is a γ-aminobutyric acid type B receptor agonist primarily used for spasticity. It is increasingly prescribed orally at high off-label doses for conditions such as alcohol use disorder, raising concerns regarding severe toxicity and withdrawal syndromes. This systematic review comprehensively characterizes the clinical presentations, management strategies, and outcomes associated with oral baclofen toxicity and withdrawal.

methodsMEDLINE, Embase, and CENTRAL databases were searched from inception through October 2024. Eligible studies included clinical trials, observational studies, case series, and case reports describing oral baclofen toxicity or withdrawal in humans. Excluded were studies on intrathecal baclofen, non-human or preclinical data, gray literature, and reports lacking sufficient clinical data. Three reviewers independently performed study screening, data extraction, and quality assessments. The Joanna Briggs Institute Critical Appraisal Checklists for case reports, case series, and observational studies were used to evaluate methodological quality and risk of bias across included studies. Discrepancies were resolved by consensus among reviewers, with senior author verification when needed. Outcome measures included clinical presentation, management strategies, need for intensive care or mechanical ventilation, length of hospital stay, recovery status, and mortality. Because of study heterogeneity, data were synthesized narratively without a formal certainty assessment.

resultsSixty-six case reports (44 toxicity cases from 38 case reports, 34 withdrawal cases from 28 case reports) and 18 retrospective studies (n = 1540) were included (total n = 1618 individuals). Baclofen toxicity commonly presented with central nervous system depression (68%), seizures (36%), and respiratory depression (21%), particularly at doses ≥ 300 mg. Management predominantly involved supportive measures, including mechanical ventilation in approximately 54.5% of cases. Full clinical recovery occurred in 97.7% of cases. In retrospective cohorts, mortality was generally low (~ 0-4%), with most patients recovering following supportive management. Baclofen withdrawal commonly manifested with severe psychiatric disturbances (up to 20.6%), delirium, agitation, and autonomic instability, typically emerging within 1-4 days after abrupt discontinuation. Rapid baclofen reinitiation consistently resolved withdrawal symptoms.

conclusionsBaclofen toxicity and withdrawal can become severe or life threatening, underscoring the need for prompt recognition and careful medical management. Clinicians should exercise caution when prescribing baclofen, particularly at higher doses (≥ 300 mg/day). Prospective studies and standardized clinical guidelines are needed to enhance patient safety and optimize outcomes. PROSPERO number CRD420251155708.

Indexed as

BaclofenGABA-B Receptor AgonistsSubstance Withdrawal SyndromeHumansOff-Label UseBaclofenGABA-B Receptor Agonists

Identifiers

PMID41555041

What Socratic holds

Textmetadata
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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 Socratic graph.