Donepezil for anticholinergic drug intoxication: a case report

Case report

A 53-year-old male was admitted to emergency service after attempting suicide by taking 1,000 mg of amitriptyline. He presented with confusion, tremor, and fasciculation on arrival. He had a long history of alcohol dependence (12 years), which had previously resulted in an alcoholic coma six years prior. Upon arrival, his blood pressure was 200/120 mm Hg and pulse was 150 beats/min. His pupils were mydriatic and reactive to light. Mucous membranes were dry, skin was warm and dry, and flushing was observed.

Gastric lavage was performed and activated charcoal 50 g was given once. Activated charcoal was not given again because it was likely longer than 12 hours since admission and possible drug consumption. Electrolytes, ABG, glucose, liver function tests, blood gases, serum pH results were within normal range except for mild elevation in liver function tests.

His first psychiatric evaluation six hours after admission showed decreased attention and awareness of self and surroundings. He had anxiety and mild psychomotor hyperactivity. Significant cognitive deficits were present and consciousness fluctuated. He was diagnosed with delirium due to anticholinergic drug intoxication according to DSM-IV.

Along with supportive care, he was prescribed haloperidol 5 mg IM or IV once a day for agitation. His consciousness progressively impaired and fluctuations continued. As his attention, awareness of the self and surrounding, and orientation decreased, his psychomotor hyperactivity increased to severe agitation necessitating restraint.

Due to his increasing delirium (as evaluated by the Trzepacz delirium-rating scale), his treating physicians decided to use a cholinesterase inhibitor. Unfortunately, physostigmine was not available in Turkey during this time, so the physicians presumed donepezil may be a substitute due to its similar effect.

The patient was admitted to the intensive care unit (ICU) on his third day of admission, and donepezil 5 mg once daily via nasogastric tube was started. The patient responded dramatically, with a clear conscious and significant verbal communication the next morning. He informed the team that he had taken 40 tablets of amitriptyline 25 mg as a suicide attempt. His delirium rating score reduced, but psychiatric evaluation continued over the next 5 days. 

Although his consciousness was clear and stable after donepezil initiation, treatment was maintained for 72 h to ensure his recovery was not spontaneous. He was discharged from the ICU after six days and referred to a psychiatric inpatient clinic.

This case report describes donepezil used for anticholinergic toxicity reversal. Donepezil was chosen because it significantly inhibits the cholinesterase in brain tissue and in serum, but does not inhibit cholinesterase in the heart and in the small intestine. Some authors consider donepezil to be more specific than physostigmine for cerebral tissue while also having fewer peripheral adverse events.

This patient responded to donepezil eight hours after administration of the first dose. Factors that may have impacted the efficacy of this include the relationship between serum acetylcholine levels and the severity of delirium symptoms and the patient’s rate of amitriptyline metabolism. While this case report may be unique, the clinical efficacy of donepezil in delirium due to anticholinergic overdose deserves further investigation.