Adverse Effects of Physostigmine

  • Ann M. ArensEmail author
  • Tom Kearney



Physostigmine is a tertiary amine carbamate acetylcholinesterase inhibitor. Its ability to cross the blood-brain barrier makes it an effective antidote to reverse anticholinergic delirium. Physostigmine is underutilized following the publication of patients with sudden cardiac arrest after physostigmine administration in patients with tricyclic antidepressant (TCA) overdoses. We completed a narrative literature review to identify reported adverse effects associated with physostigmine administration.


One hundred sixty-one articles and a total of 2299 patients were included. Adverse effects occurred in 415 (18.1%) patients. Hypersalivation (206; 9.0%) and nausea and vomiting (96; 4.2%) were the most common adverse effects. Fifteen (0.61%) patients had seizures, all of which were self-limited or treated successfully without complication. Symptomatic bradycardia occurred in 8 (0.35%) patients including 3 patients with bradyasystolic arrests. Ventricular fibrillation occurred in one (0.04%) patient with underlying coronary artery disease. Of the 394 patients with TCA overdose, adverse effects were described in 14 (3.6%). Adverse effects occurred in 7.7% of patients treated with an overdose of an anticholinergic agent compared with 20.6% of patients with non-anticholinergic agents. Five (0.22%) fatalities were identified.


In conclusion, significant adverse effects associated with the use of physostigmine were infrequently reported. Seizures were self-limited or resolved with benzodiazepines, and all patients recovered neurologically intact. Physostigmine should be avoided in patients with QRS prolongation on EKG, and caution should be used in patients with a history of coronary artery disease and overdoses with QRS prolonging medications. Based upon our review, physostigmine is a safe antidote to treat anticholinergic overdose.


Physostigmine Antidote Antimuscarinic Delirium Review 


Sources of Funding


Compliance with Ethical Standards

Conflicts of Interest


Supplementary material

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Copyright information

© American College of Medical Toxicology 2019

Authors and Affiliations

  1. 1.Minnesota Poison Control SystemMinneapolisUSA
  2. 2.Hennepin Healthcare, Department of Emergency MedicineHennepin County Medical CenterMinneapolisUSA
  3. 3.California Poison Control System, San Francisco DivisionSan FranciscoUSA
  4. 4.San Francisco School of PharmacyUniversity of CaliforniaSan FranciscoUSA

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