CASE 1

A CASE REPORT ON ANTICHOLINERGIC TOXICITY: REVISITING MASQUERADES OF ANTICHOLINERGIC AGENTS

Case contributed by 

Nithya Nagalingam, Lau Kit Mun, Siti Nor Fadhlina binti Misron

Introduction 

Anticholinergic delirium is often an underreported and underdiagnosed condition in a psychiatric setting. Many psychiatric medications have anticholinergic property which acts especially at the muscarinic receptor. The symptoms masquerade relapse primary psychiatric disorder or serotonin syndrome causing a delay in management. Early recognition and intervention may prevent severe manifestation of anticholinergic toxicity. These two cases illustrates these masquerades and the authors hope that psychiatrists could be more vigilant in identifying and diagnosing impending/full-blown anticholinergic toxicity. 

Case presentation 

Case 1
A 26-year-old male with underlying mild intellectual disability was admitted for relapse major depressive disorder with psychosis. Initial medications given were Haloperidol, Promethazine, Midazolam, Zuclopenthixol Decanoate, Olanzapine, Amisulpride and Clonazepam. Following these medications, he developed persistent tachycardia since his third day of admission. There were several changes of medications (Diazepam, Escitalopram, Mirtazapine, Aripiprazole and Benzhexol) throughout his stay that contributed to the worsening of psychosis and dystonia. He was initially thought to have worsening of psychosis and later serotonin syndrome. After 9 days of admission, he developed urinary retention, constipation, fever, and dry skin. By this time, he needs to be transferred to the medical ward. All medications were stopped and supportive treatment administered. The symptoms abated after 1 week. A this stage, the diagnosis of anticholinergic toxidrome is irrefutable. The temporal association between medications and emergence of signs and symptoms od anticholinergic toxidrome is illustrated in Figure 1(a). 

Case 2
A 21-year-old male was admitted for substance-induced psychosis whereby he had been abusing kratom and cannabis on a daily basis. Within the first 3 days of admission, he was given medications such as Haloperidol, Procyclidine, Risperidone, Benzhexol, Promethazine, Midazolam and Clonazepam. Since then, he had been persistently having raised pulse rate of 90-98 bpm as opposed to his baseline 66-84 bpm. Initially, the delirium was misdiagnosed as worsening of psychosis. Thus, he was given IM Promethiazine as tranquilizer which only worsened his anticholinergic delirium. On the third day, he started to have changes of symptoms such as irrelevant speech, picking up imaginary objects, wearing clothing backwards, constipation, disorientation, and dilated pupils. He was diagnosed as anticholinergic delirium. All medications were ceased and adequate hydration was administered. He was treated in psychiatric ward as the signs and symptoms are not life-threatening and resolving fast. Complete resolution of symptoms was achieved 3 days after the cessation of medication. The temporal association between medications and emergence of signs and symptoms od anticholinergic toxidrome is illustrated in Figure 1(b). 

Discussion 

Anticholinergic toxidrome is undoubtedly underreported psychiatric emergency in view of its masquerades as illustrated in these two cases. These symptoms in the inexperienced eyes can be easily mistaken for worsening of psychosis, extrapyramidal side effect of antipsychotics and serotonin syndrome. The reason being the similarities of the clinical presentation especially during the initial stage of toxicity (as illustrated in Figure 2). Therefore, it is essential for psychiatrist to familiarize themselves with pharmacodynamic properties of psychiatric medications and established the temporal relationship with emergence of new symptoms as illustrated in figure 1. 

Anticholinergic agents exert its affect by antagonizing the acetylcholine neurotransmitters at muscarinic receptors. Acetylcholine is the neurotransmitter involved in autonomic nervous system predominantly the parasympathetic pathway. The antagonist action resulted in the attenuation of sympathetic activities and suppression of parasympathetic activities [1] 

Anticholinergic toxidrome can be divided into peripheral and central syndrome. The peripheral anticholinergic syndrome is frequently characterized by hyposalivation/decreased secretions, slow gastric motility, urinary retention, mydriasis resulting in blurred vision or the acute precipitation of narrow-angle glaucoma, heat intolerance usually resulting in hyperthermia, and cardiovascular changes such as tachycardia and widened pulse pressures. The central anticholinergic syndrome is most commonly manifested as agitation that may progress to a hyperactive (agitated) delirium, often with pressured, incoherent speech, and visual and/or auditory hallucinations [2]. 

There are enormous number of psychiatric medications that possess the anticholinergic property and this ranges from the medications as tranquilizing agents, sedative-hypnotic agents, antipsychotics, antidepressants, antimuscarinics, and anti-Parkinson drugs [2]. In case 2, the anticholinergic effects attenuated because the cannabis has anticholinergic property [3] whereas kratom has alpha-adrenergic agonist property [4]. Figure 1 highlighted all the medications with anticholinergic property delivered to both patients. The symptoms and the medications had been arranged in chronological order to help established the temporal association between the emergence of symptoms and the deliverance of the anticholinergic agents. 

These cases highlighted the importance of anticholinergic toxidrome early detection. The earlier is the condition identified, the earlier the anticholinergic agents would be withdrawn, and thus the earlier the symptoms resolved. In Case 2 the condition was detected early before the any life-threatening signs or symptoms emerged. Thus, the anticholinergic toxidrome abated early ensuring that the antipsychotic resumed early and discharge can be commenced. 

Conclusion 

Many psychiatric medications possess antagonistic effect towards multiple acetylcholine receptor. This results in parasympathetic suppression and noradrenaline surge activities. This condition is reversible once all anticholinergic agents are ceased. Therefore, doctors in psychiatric services shall consider to treat suspected impending anticholinergic toxidrome rather than awaiting full-blown symptoms uncovered before initiating the treatment. Furthermore, the benefit of identifying this toxidrome early and treat it early far outweigh the disadvantages. 

Acknowledgment 

Thank you Dr Norazam bin Harun, director of Hospital Permai for his support 

References 

1. Broderick      ED, Metheny H, Crosby B. Anticholinergic Toxicity. [Updated 2022 May 1].      In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;      2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534798/ 
2. Boroughf      W.J. Anticholinergic Syndrome. In: Brent J. et al. (eds) Critical Care      Toxicology. Springer, Cham. . 2017. https://doi.org/10.1007/978-3-319-17900-1_133      
3. Mangot      AG. Bad trip due to anticholinergic effect of cannabis. Gen Hosp      Psychiatry. 2013;35(6):682.e5-6. doi: 10.1016/j.genhosppsych.2013.06.010 
4. Nelsen      JL, Lapoint J, Hodgman MJ, et al. Seizure and Coma Following Kratom      (Mitragynina speciosa Korth) Exposure. J. Med. Toxicol. 2010;6:424–426. https://doi.org/10.1007/s13181-      010-0079-5 

PUBLISHED ON 12/04/2025