Tizanidine Withdrawal Syndrome: Clinical Manifestations and Management Strategies. Case Series

Tizanidine, an imidazole derived α2 adrenergic agonist, is widely prescribed for spasticity and chronic musculoskeletal pain. Abrupt discontinuation can precipitate withdrawal syndromes characterized by sympathetic overactivity. Although pharmacologically plausible, this phenomenon is potentially underreported in clinical practice. We describe four patients with diverse comorbidities who developed acute tizanidine withdrawal. All cases were directly observed at a single tertiary care center and identified during routine inpatient clinical practice over a defined timeline. Case 1 was a 24 year old female admitted with empagliflozin induced diabetic ketoacidosis who experienced hypertensive crisis and tachycardia following abrupt cessation of chronic high dose tizanidine. Case 2 was a 29 year old female with Crohn's disease who developed tremors, anxiety, and autonomic instability after reducing her regimen from 40 mg nightly to 16 mg daily. She had self-discontinued her last dose prior to presentation. Case 3 was a 29 year old female with recurrent pancreatitis, resistant hypertension, and an adrenal incidentaloma who presented with severe hypertension and tremors after discontinuing both tizanidine and diazepam. Symptoms began within approximately 24 h of abrupt cessation. Case 4 was a 42 year old male with asthma, hypertension, anxiety disorder, bariatric surgery, methamphetamine use, and more than ten prior admissions specifically for tizanidine withdrawal, who presented with palpitations, tremors, vomiting, and hypertensive crisis after abrupt dose reduction. In all cases, reintroduction of tizanidine followed by a structured tapering regimen resulted in clinical stabilization. These cases highlight the clinical significance of tizanidine withdrawal, its diverse presentations, and the importance of cautious tapering. Patient education on avoiding abrupt discontinuation is essential, particularly for individuals with psychiatric comorbidities or prior withdrawal episodes. Awareness of this underrecognized syndrome is critical to prevent misdiagnosis and ensure safe prescribing practices.