Prolonged Agitation and Hypotonia due to Baclofen and Tizanidine Overdose Followed by Withdrawal: A Case Report

We describe a unique case of combined baclofen and tizanidine overdose followed by dual withdrawal syndromes, highlighting overlapping and contrasting clinical features that may complicate diagnosis and management. A 26-year-old man with paraplegia from cervical spinal cord injury, prescribed baclofen and tizanidine for spasticity, was found unresponsive at home next to partially empty medication bottles. Clinical evaluation included laboratory testing, neuroimaging, continuous monitoring, and serial neurologic and cardiopulmonary assessments. On admission, the patient exhibited CNS depression, hypotension, bradycardia, hypothermia, and subsequent episodes of severe psychomotor agitation. Supportive care with fluids, vasopressors, and sedation was required, including 2 subsequent intubations for airway protection. Within 24 hours, fever, tachycardia, and worsening agitation developed, consistent with withdrawal. Reintroduction of home baclofen and tizanidine alongside benzodiazepines and dexmedetomidine led to gradual resolution of symptoms, and the patient was discharged at neurologic baseline with psychiatric follow-up. This case underscores the diagnostic and therapeutic challenges of overlapping baclofen and tizanidine toxicity and withdrawal. Recognizing key bedside features-such as hypotonia vs tremor and mydriasis vs miosis-is essential. Sedation and bradycardia may be more severe in combined overdose than in overdose of either agent alone. Clinicians should anticipate withdrawal even in the setting of persistent toxicity. Early recognition and tailored supportive care are the cornerstone of management.