Late-Onset Delirium After an Overdose of Acetaminophen in a Case of Benzodiazepine Dependence

To the Editor: A 42-year-old man with depression overdosed on acetaminophen 37.5g and was admitted to our hospital. He had been taking flunitrazepam 12 mg, etizolam 5 mg, clotiazepam 15 mg, lormetazepam 6 mg, every day for over a year. He was diagnosed with acetaminophen intoxication and benzodiazepine (BZD) withdrawal. Gastric lavage was carried out, and N-acetylcysteine was administered, with mild hepatic dysfunction. Because his delirium did not improve, he was admitted to the psychiatric ward on Day 5. Although his delirium became aggravated after an attack of grand mal convulsions on Day 6, his delirium completely disappeared on Day 10. Electroencephalographic examination (EEG) on Day 12 was normal; hepatic dysfunction had also improved upon biochemical testing carried out on Day 14, with no observation of other abnormalities, and discharge from the hospital was planned. However, disorientation and visual hallucinations were observed from Day 18, with no contributing factors, and the patient returned to a state of delirium state once again. No abnormalities were observed on the head CT scan and blood/biochemical testing on Day 20. Slowing of brain waves was observed on EEG compared with that of Day 12. Subsequently, although his delirium continued for over 2 weeks, the delirium completely disappeared on Day 40, and slowing of brainwaves was improved upon EEG. The delirium did not recur after then, and the patient left the hospital.

Various types and amounts of BZD withdrawal and acetaminophen intoxication may be considered as the cause for the initial delirium. Delirium and seizures are well known as major withdrawal symptoms of BZD. Acetaminophen can cause delirium in pediatric patients,¹ but there are very few reports on the effects of acetaminophen on the central nerves in adults. The lethal dose of acetaminophen is 13g to 25g, but an amount exceeding this was taken in this case, and it cannot be ruled out that intoxication due to acetaminophen caused the delirium. However, the cause of the second delirium episode should be open to discussion. The first delirium was completely clinically improved, and EEG on Day 12 was normal. Afterward, delirium occurred again, even though other new physical complications did not occur. There have been no reports in which withdrawal delirium from BZD occurred after once recovering. Furthermore, delirium was prolonged for a long period of time in elderly patients and dementia patients;² however, there are no reports similar to this case, in which withdrawal delirium from BZD continued for a total of 40 days, combining the first and second episodes, in a relatively young patient with no underlying physical disorders. Therefore, we believe that the lethal dose of acetaminophen intoxication caused the second delirium. Because acetaminophen intoxication can cause delirium, clinicians should pay attention to side effects other than its liver dysfunction.