Benzodiazepine Withdrawal Masked by Clonidine: An Emergency Presentation With a Diagnostic Challenge

Background: Benzodiazepines are central nervous system depressants that act on GABA-A receptors and enhance the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Prolonged use of benzodiazepines carries a high risk of physiological dependence and abrupt discontinuation following high-dose or long-term benzodiazepine use may precipitate withdrawal. Benzodiazepine withdrawal symptoms include autonomic hyperarousal (e.g., tachycardia, hypertension, sweating and tremors), anxiety, insomnia, confusion and rarely psychotic features including delusions and hallucinations. Clonidine is an α 2 -adrenergic agonist that has sympatholytic activity and thereby attenuates the features of autonomic hyperarousal. In a person who is on regular clonidine, benzodiazepine withdrawal symptoms may be masked by clonidine, resulting in a diagnostic dilemma. Case: A 35-year-old man with no significant past psychiatric history presented to the Emergency Department with confusion, persecutory delusions, auditory and visual hallucinations, and bradycardia (40-45 bpm) for 3 days. He underwent a below-knee amputation a few months ago following complications of a crush injury. He had been on multiple medications for post-amputation pain and had abruptly ceased long-term diazepam a week before his current presentation. Organic screening for delirium, metabolic and infective causes were unremarkable. The presentation was suggestive of benzodiazepine withdrawal psychosis; however, persistent bradycardia was inconsistent with the typical autonomic hyperarousal seen in benzodiazepine withdrawal. A thorough medication review revealed concomitant administration of clonidine, and a diagnosis of benzodiazepine withdrawal masked by clonidine’s sympatholytic effect was made. With recommencement and titration of benzodiazepines, psychosis and confusion resolved within 24 hours. Discussion: This case highlights the need for awareness of drug interactions that may mask typical withdrawal symptoms of benzodiazepines. Furthermore, it emphasises the need for thorough collateral history particularly when the patient is incapacitated and highlights the importance of addressing complex pain needs to prevent self-medication.