2026 American Academy of Neurology Abstract Website

Minahil Iqbal¹, Kush Sehgal², Parth Modi³, Gabriel P. A. Costa⁴, Gargi Bhattacharya⁵, Neil Nero⁶, Junaid H Siddiqui⁷, Jeremy Weleff⁸, Akhil Anand⁹
¹Allama Iqbal Medical College, Lahore, ²Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India, ³Medical College Baroda, Gujarat, India, ⁴Yale University School of Medicine, New Haven, CT, USA, ⁵Stanford University, Stanford, CA, USA, ⁶Cleveland Clinic, ⁷Department of Neurology, Cleveland Clinic, OH, United States, ⁸University of Alberta, Edmonton, AB, Canada, ⁹Department of Psychiatry and Psychology, Cleveland Clinic, Cleveland, OH, USA

Objective:

To systematically review and characterize the clinical features, management strategies, and outcomes of oral baclofen toxicity and withdrawal, providing a comprehensive synthesis to guide clinical practice and improve patient safety.

Background:

Baclofen is a GABA-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.

Design/Methods:

MEDLINE, Embase, and CENTRAL databases were searched from inception through October 2024. Eligible studies included clinical trials, observational studies, case series and case reports. Three reviewers independently performed data extraction and quality assessments using the Joanna Briggs Institute (JBI) critical appraisal checklists for case reports and case series. Findings were synthesized narratively.

Results:

Sixty-six case reports (44 toxicity cases from 38 case reports, 34 withdrawal cases from 28 case reports) and 18 retrospective studies (n = 1,540) were included. Baclofen toxicity commonly presented with CNS depression, coma, seizures, and cardiovascular instability, particularly at doses ≥300 mg. Management predominantly involved supportive measures, including mechanical ventilation. Full clinical recovery occurred in 97.7% of cases; overall mortality was 2.3%. Baclofen withdrawal commonly manifested with severe psychiatric disturbances, delirium, agitation, and autonomic instability. Rapid baclofen reinitiation consistently resolved withdrawal symptoms.

Conclusions:

Baclofen 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.