Delirium secondary to anticholinergics

Background

Antipsychotics are the mainstay of treatment of psychosis. They are well known for their extrapyramidal side effects (EPSEs) that greatly impact a patient’s well-being, including stiffness, tremor, difficulty eating and writing. Procyclidine is commonly prescribed to alleviate EPSEs. It does so by inhibiting the action of acetylcholine at the muscarinic receptor, hence minimising its excitatory effects.1

Reported side effects of procyclidine include most commonly drowsiness, dizziness, constipation, flushing, nausea, nervousness, blurred vision and dry mouth. Rarely, it is reported to cause abdominal pain, difficulty swallowing, urinary retention, weakness, chest pain, fainting, fever, tachycardia, arrhythmias, change in mental state (such as confusion, hallucinations, memory problems), mydriasis and visual changes.1 2

Being an anticholinergic, anticholinergic delirium is a possible, although rare, adverse effect of procyclidine. Following the use of Adverse Drug Reaction Probability Scale,3 this case report illustrates a probable procyclidine-induced delirium in a young adult man.

Case presentation

A man in his early 30s was initially referred from the health clinic to the Accident & Emergency Department (A&E)accompanied by the police in view of bizarre behaviour, agitation and paranoia towards other people. On mental state examination, the patient was noted to have symptoms of thought insertion, broadcast and withdrawal. Elements of persecutory delusions were also noted, and these resulted in aggressive and agitated behaviour that required rapid tranquilisation.

This was the patient’s first presentation with psychosis. Physical examination at A&E was unremarkable and an organic screen was carried out including blood tests and a CT brain. Results obtained from this organic screen were all within normal limits. A drug urine analysis was also done, and it came positive for synthetic cannabinoids. In keeping with these findings, the working diagnosis at this point was substance-induced psychosis.

Eventually, the patient was transferred to a psychiatric hospital where he was started on regular intramuscular haloperidol and lorazepam to help with agitation, as initially he was refusing oral treatment. The patient’s psychiatric state improved gradually, and he eventually started cooperating with the administration of oral antipsychotics and benzodiazepines. Eventually, risperidone was also added to aid with the persistent delusions and paranoia. After weeks of adjusting treatment dosages, the patient showed a significant improvement in his mental state. However, 8 weeks into the admission, he started to report about generalised stiffness and jaw-locking on chewing. This was treated as a side effect from the antipsychotics and he was thus started on regular procyclidine at 5 mg two times per day.

Within 3 days of commencement of regular procyclidine, the nursing staff started to notice subtle changes in the patient’s behaviour. Initially, episodes of staring and mumbling were noted. His bizarre behaviour became progressively worse with increasing episodes of talking to himself and with speech becoming progressively slurred, up to a point that it was almost incomprehensible. He started to experience disorientation, paranoid delusions and visual hallucinations. He was noted to be responding to these external stimuli by feeding cats and dogs, which were not actually present. He became increasingly hostile, agitated and uncooperative with the staff in fact, he required transfer to a secure and closed ward.

Physical examination showed increased tone in all four limbs as well as dilated pupils. However, he remained afebrile and haemodynamically stable. An organic screen, which included urgent blood investigations, a 12-lead ECG, urinalysis for bacteria and for drug screen were all performed. All results were within normal limits.

This presentation (disorientation, visual hallucinations, behavioural change) was consistent with that of delirium, however, the cause was unclear. While reviewing the patient’s file, it was noted that there was a correlation between the introduction of regular administration procyclidine and the deterioration in the patient’s state.

Procyclidine was stopped and immediate improvement in the patient’s mental state was noted. Within 2 days of discontinuing procyclidine, the patient’s mental state returned to normal; he was oriented to time, place and person, and he stopped experiencing visual hallucinations and paranoia.

Investigations

On the patient’s initial presentation at the Emergency department, an organic screen was carried out. This included a 12-lead ECG, baseline blood tests (complete blood count, renal profile, C reactive protein, serum electrolytes, thyroid function tests, liver function tests, lipid profile, coagulation screen), urinalysis and CT brain. Urine was also tested for drugs of abuse and sent for a toxicology screen.

An organic screen was repeated once again when the patient presented in a delirious state to exclude underlying organic pathology causing or contributing to the delirium.

Outcome and follow-up

The patient remained an inpatient for a number of months after this episode mainly due to social issues that had to be settled prior to discharge. The patient was seen regularly during ward rounds and remained well after stopping the regular administration of procyclidine. After 3 months, he was discharged to the community with frequent outpatient follow-up appointments (every 2 weeks) and also involved the outreach community mental health team to ensure regular reviews of his mental state and adherence to treatment.