Is Abrupt Withdrawal of Benzodiazepines a Risk Factor for Neuroleptic Malignant Syndrome? A Case Report With Single-Dose Haloperidol

Abstract

Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction associated with the use of dopamine-modulating agents, which presents with symptoms like high fever, muscle rigidity, and autonomic instability. It is known that both the use of dopamine receptor antagonists and the sudden withdrawal of dopamine receptor agonists can trigger NMS. Benzodiazepine withdrawal can create a GABA-deficient state, linked to catatonia and possibly predisposing individuals to NMS. The case was a 53-year-old male patient with a history of high-dose benzodiazepine dependency, who developed NMS after the abrupt withdrawal of alprazolam and the single-dose intramuscular (IM) haloperidol. He presented with the symptoms of stupor, generalized rigidity, and fever, requiring admission to the Respiratory Care Unit. His medical history included long-term use of clonazepam, alprazolam, and methadone maintenance therapy (MMT). The laboratory findings also demonstrated elevated creatine phosphokinase (CPK) levels, peaking at 7896 IU/L. The treatments with bromocriptine and lorazepam further led to gradual improvement, and the patient was discharged after 11 days following the resolution of NMS symptoms. This case highlights the potential role of benzodiazepine withdrawal as a risk factor for NMS, especially when combined with antipsychotic medication like haloperidol. The shared mechanisms between the pathophysiology of NMS and benzodiazepine withdrawal suggest that the abrupt cessation of GABAergic agents may lower dopaminergic activity, contributing to the onset of NMS. Clinicians must be accordingly cautious in distinguishing benzodiazepine withdrawal from other causes of delirium and then option for appropriate treatment approaches to mitigate risks.