European Journal of Cardiovascular Medicine

Anticholinergic tertiary amine, is widely used as an anti-spasmodic agent for conditions such as irritable bowel syndrome, dysmenorrhea, and motion sickness. As it is tertiary amine can cross the blood-brain barrier, affecting central muscarinic receptors can cause physical dependence.1 Muscarinic acetylcholine receptors (mAChRs), which are G-protein-coupled receptors, are crucial in mediating various CNS functions such as cognition, memory, and reward.2 All five subtypes of mAChRs are expressed in the CNS, with M1, M2, and M4 receptors prominently involved in the brain.3 Dicyclomine's anticholinergic action can disrupt normal mAChR signalling, particularly affecting M1, which can be implicated in psychotic symptoms.4 Earlier literature is very scant regarding dicyclomine-induced psychosis, and there is a need for more research in this aspect on which the current study focuses on.

Case 1

A 4.5-year-old male was referred to the psychiatry ward from pediatrics with complaints of visual hallucinations and irritability. History of Presenting Illness: The patient was initially treated by a local physician for abdominal pain with an intramuscular injection of 10ml of Cyclopam (dicyclomine). Approximately three hours post-injection, the patient began experiencing visual hallucinations and irritability. The symptoms were progressive and persistent, failing to subside after 24 hours. Due to the persistence and severity of the symptoms, the patient was evaluated by a pediatrician, who subsequently referred him to the psychiatric ward for further assessment. Birth History: The patient was born out of a nonsconsanguineous marriage. Psychiatric History: No history of psychiatric illness. Medical History: No other medical comorbidities were noted.On examination, Orientation: The patient was oriented to time, place, and person. General Appearance: Eye contact was initiated and maintained. Rapport was established with the examiner. Psychomotor Activity (PMA): Increased Speech: Tone: Increased, Volume: Increased, Spontaneity: Spontaneous, Coherence: Coherent but irrelevant. Thought Process: The patient exhibited overvalued ideas of persecution. Perception: Visual hallucinations were present. Investigations included Complete Blood Count (CBC), Liver Function Tests (LFT), Renal Function Tests (RFT), and serum electrolytes, all of which were within normal limits. The Delirium Rating Scale-Revised-98 (DRS-R-98) was applied to rule out delirium. Symptoms resolved within 2 days of risperidone 0.25mg, as, in the absence of a clear etiology for delirium, dicyclomine was identified as the probable cause of the psychotic symptoms.

CASE-2

A 16-year-old female presented to the psychiatry outpatient department accompanied by her parents, with complaints of auditory hallucinations occurring intermittently for the past four months. These hallucinations were described as persistent voices heard throughout the day and occurred 3–4 days per month, exclusively during her menstrual periods. The patient attained menarche at the age of 15 years. There was no history of psychiatric illness in the past, no prior medical or surgical illnesses, and no family history of psychiatric disorders. Her birth and developmental history were normal. Orientation: The patient was oriented to time, place, and person. General Appearance: Eye contact was initiated and maintained. Rapport was established with the examiner. Psychomotor Activity (PMA): normal Speech: Tone: normal, Volume: normal, Spontaneity: Spontaneous, Coherence: Coherent and relevant. Thought Process: No abnormality found. Perception: Second-person auditory hallucinations were present. General and neurological examinations were unremarkable, and routine blood investigations, including complete blood count, liver and renal function tests, electrolytes, and thyroid profile, were within normal limits.

She was started on risperidone 2 mg/day. The hallucinations subsided within a week. However, on follow-up, similar symptoms reappeared during her next menstrual cycle. On reviewing her medication history, it was found that approximately three months after menarche, she began experiencing moderate to severe dysmenorrhea. Based on the advice of a peer, she began taking dicyclomine (10 mg per tablet), consuming 2–3 tablets per day during menstruation without medical supervision. The medication was discontinued, and she was advised to use mefenamic acid for dysmenorrhea instead. Subsequently, the auditory hallucinations did not recur over the next three menstrual cycles, and risperidone was successfully tapered and stopped.

CASE-3

A 19-year-old male was brought to the psychiatry outpatient department by his parents with complaints of hearing voices and the abnormal sensation that someone was sitting on him. These symptoms had an abrupt onset one day prior to presentation. The patient had a 4-year history of alcohol use, consuming approximately 6 units three times a week since the age of 15. His alcohol use was associated with school absenteeism, family conflict over money, and irritability when denied money. About a year ago, under peer influence, he began using alprazolam tablets, consuming 3–4 tablets of 0.5 mg strength approximately 4–5 times a week, particularly when short of money for alcohol. More recently, after being denied alprazolam by local pharmacies due to a lack of a prescription, he began using prochlorperazine (THP) 2 mg tablets, ingesting 7–8 tablets the day before the onset of psychotic symptoms. On mental status examination, the patient was alert and oriented to time, place, and person. There was no evidence of formal thought disorder, mood symptoms, or cognitive deficits. However, he exhibited perceptual disturbances, including second-person auditory hallucinations and a tactile hallucination of someone sitting on him. There was no history of head injury, seizures, or other medical illness. A 19-year-old male was brought to the psychiatry outpatient department by his parents with complaints of hearing voices and the abnormal sensation that someone was sitting on him. These symptoms had an abrupt onset one day prior to presentation.

The patient had a 4-year history of alcohol use, consuming approximately 6 units three times a week since the age of 15. His alcohol use was associated with school absenteeism, family conflict over money, and irritability when denied money. About a year ago, under peer influence, he began using alprazolam tablets, consuming 3–4 tablets of 0.5 mg strength approximately 4–5 times a week, particularly when short of money for alcohol. More recently, after being denied alprazolam by local pharmacies due to a lack of a prescription, he began using Trihexyphenidyl (THP) 2 mg tablets, ingesting 7–8 tablets the day before the onset of psychotic symptoms. On mental status examination, the patient was alert and oriented to time, place, and person. There was no evidence of formal thought disorder, mood symptoms, or cognitive deficits. However, he exhibited perceptual disturbances, including second-person auditory hallucinations and a tactile hallucination of someone sitting on him. There was no history of head injury, seizures, or other medical illness. He was admitted and started on Olanzapine 5 mg once daily and Lorazepam 2 mg three times daily. Over the next 48 hours, his psychotic symptoms resolved significantly, and he reported improved sleep and reduced anxiety. Olanzapine was successful tappered.

Anticholinergic drugs are commonly prescribed for various medical conditions and can cause peripheral side effects like urinary retention, constipation, and cycloplegia few case reports state anticholinergic central toxicity effects like delirium, depression, elation, and hallucinations These reports are mostly in older people Some studies are done on Alzheimer’s patients dose dependent psychosis with anticholinergic⁵. The Cholinergic hypothesis states that a cholinergic deficit in the central nervous system can lead to psychosis.⁶ These lead to a hypothesis of treatment of psychosis with cholinergic drugs, as the case study is on single-institute findings cannot be generalized. Further research is needed on anticholinergic-induced psychosis at a multicentric level for a better understanding of the results.

Anticholinergic drugs are commonly prescribed for various medical conditions and can cause peripheral side effects like urinary retention, constipation, and cycloplegia few case reports state anticholinergic central toxicity effects like delirium, depression, elation, and hallucinations These reports are mostly in older people Some studies are done on Alzheimer’s patients dose dependent psychosis with anticholinergic⁵. The Cholinergic hypothesis states that a cholinergic deficit in the central nervous system can lead to psychosis.⁶ These lead to a hypothesis of treatment of psychosis with cholinergic drugs, as the case study is on single-institute findings cannot be generalized. Further research is needed on anticholinergic-induced psychosis at a multicentric level for a better understanding of the results.

Anticholinergic drugs are commonly used. Psychiatrists must be open to the possibility that anticholinergic psychosis treatment is a stoppage of the drug, and it is temporary. Detection reduces the burden of antipsychotic usage of antipsychotics in childhood.

1. Das S, Mondal S, Datta A, et al. A rare case of dicyclomine abuse. J Young Pharm JYP 2013; 5: 106–107.
2. Szczurowska E, Szánti-Pintér E, Chetverikov N, et al. Modulation of Muscarinic Signalling in the Central Nervous System by Steroid Hormones and Neurosteroids. Int J Mol Sci 2022; 24: 507.
3. Volpicelli LA, Levey AI. Muscarinic acetylcholine receptor subtypes in cerebral cortex and hippocampus. Prog Brain Res 2004; 145: 59–66.
4. Kilbinger H, Stein A. Dicyclomine discriminates between M1- and M2-muscarinic receptors in the guinea-pig ileum. Br J Pharmacol 1988; 94: 1270–1274.
5. Cancelli I, Valentinis L, Merlino G, et al. Drugs with anticholinergic properties as a risk factor for psychosis in patients affected by Alzheimer’s disease. Clin Pharmacol Ther 2008; 84: 63–68.
6. Cummings JL, Back C. The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer’s disease. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry 1998; 6: S64-78.