Acute Pancreatitis Following Alprazolam Overdose: A Case Report and Literature Review

Background: Drug-induced acute pancreatitis is a rare but clinically significant complication. Benzodiazepines (BZD) carry a low evidentiary tier in established drug causality classifications, yet pharmacovigilance data suggest a measurable association with acute pancreatitis risk, particularly in the overdose setting. We report a case of alprazolam-induced acute pancreatitis diagnosed incidentally in a comatose patient, discuss the pathophysiological mechanisms, apply a structured causality assessment, and review the relevant literature. Case Presentation: A 40-year-old woman with no prior medical history was admitted six hours after the intentional ingestion of 20 tablets of alprazolam 0.5 mg (total dose: 10 mg) in a suicide attempt. She presented with altered consciousness (GCS 11/15), bilateral miosis, hypoxemia (SpO2 85% on room air), and tachycardia (HR 100 beats/min). Arterial blood gas analysis revealed severe respiratory acidosis (pH 7.11, PaCO2 94 mmHg). Laboratory workup demonstrated a markedly elevated serum lipase level of 311 IU/L (reference range: 7–60 IU/L for our institution), with no biliary, alcoholic, metabolic, or other drug-related etiology identified. Abdominal CT confirmed acute pancreatitis classified as mCTSI 2 (Balthazar grade C). Causality assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded a score of 5 (probable). The clinical course was complicated by moderate ARDS, aspiration pneumonia, and transient hepatic cytolysis. The patient was transferred to the ICU and successfully extubated on day 25. Conclusion: This case highlights acute pancreatitis as a rare but genuine complication of BZD overdose, detectable only through systematic lipase screening in patients with impaired consciousness. Two mechanisms are proposed: direct TSPO-mediated acinar cell toxicity and hypoxia-mediated microvascular injury, likely acting synergistically in the massive overdose context. Systematic serum lipase measurements should be considered in the workup of severe drug intoxications.