Physostigmine reversal of delirium from second generation antipsychotic exposure: a retrospective cohort study from a regional poison center.

Introduction: Physostigmine is an effective antidote for antimuscarinic delirium. There is little evidence for its use to reverse delirium following second generation antipsychotic exposure. The purpose of this study is to describe the safety and effectiveness of physostigmine in reversing delirium from second generation antipsychotic exposure.

Methods: This is a retrospective cohort study of all patients reported to a single regional poison center treated with physostigmine following a second generation antipsychotic exposure from January 1, 2000 to April 15, 2021. The poison center electronic medical record was queried to identify cases and for data abstraction. The primary outcome was the positive response rate to physostigmine, as determined by two trained abstractors. Secondary outcomes included physostigmine dosing, and adverse events.

Results: Of 147 charts reviewed, 138 individual patients were included, and the response to physostigmine was reported in 128 patients. The most common second-generation antipsychotic exposure was quetiapine (97; 70.3 percent). A positive response to physostigmine was noted in 106/128 (82.8 percent) patients [95 percent confidence interval 68.9-83.6 percent]. Median number of physostigmine doses was 1 (interquartile range 1-3; range 1-9). The median total physostigmine dose received was 2 mg (interquartile range 2-6 mg; range 0.15-30 mg). The positive physostigmine response rate for patients with an antimuscarinic co-ingestion was not significantly different compared to patients with a different co-ingestion or no co-ingestion (25/34 versus 81/94; P = 0.09). Adverse events were reported in four (2.9 percent) patients, including one death.

Discussion: A positive response to physostigmine to treat antimuscarinic delirium from second generation antipsychotic exposure was reported in 82.8 percent of patients, which is similar to previous physostigmine studies. Adverse events were infrequent, and included diaphoresis (one 0.7 percent), seizure (one; 0.7 percent), and bradycardia (one; 0.7 percent). One (0.7%) patient suffered a cardiac arrest 60 minutes after receiving physostigmine to treat antimuscarinic delirium following having received increasing clozapine doses over the previous month.

Conclusions: In this study, physostigmine appears to be a safe and effective treatment for antimuscarinic delirium from second generation antipsychotic exposure. Further studies are needed to validate the safety and effectiveness of physostigmine for this indication.