Physostigmine use in clozapine intoxication from adulterated heroin: an atypical toxidrome with an effective antidote

Abstract

Anticholinergic toxicity results from a multitude of toxins and other agents. Clozapine is an uncommon cause. We describe a case of anticholinergic toxicity secondary to acute clozapine overdose from adulterated heroin with successful reversal by physostigmine. We highlight how the case presented, unique departures from the typical anticholinergic toxidrome in clozapine overdose and the benefits of using physostigmine in our patient.

Physostigmine for Facilitation of Care in Clozapine-Associated Anticholinergic Delirium

“…Two prior case reports and 1 retrospective review suggest initial dosing of 2 mg IV for reversal of clozapine delirium. 6,7,13 Rasimas et al 13 recommend predosing with lorazepam 1 to 2 mg in patients with elevated seizure risk. This is a reasonable precaution, although one must balance the probability of seizure onset with that of worsening delirium due to benzodiazepines.…”

“…Seizure is a complication of both cholinergic and clozapine toxicity. Two prior case reports and 1 retrospective review suggest initial dosing of 2 mg IV for reversal of clozapine delirium 6,7,13 . Rasimas et al 13 recommend predosing with lorazepam 1 to 2 mg in patients with elevated seizure risk.…”

“…This has been previously demonstrated in only 2 case reports. 6,7 We describe a case of clozapineassociated anticholinergic delirium wherein physostigmine administration facilitated diagnosis, extubation, and treatment trajectory. We discuss dosing and safety, then propose a practical algorithm.…”

“…5 These agents are also problematic concerning their adverse effects profile, mostly because of their neuropsychiatric adverse effects, such as headaches, sleep disturbances, depression, mania, and psychosis. 6 Atovaquoneproguanil (Malarone) is one of the most recently recommended alternative strategies for chemoprophylaxis and consists of a fixed association of atovaquone, which inhibits the mitochondrial electron transport and disrupts the mitochondrial membrane potential of the parasite, and proguanil, whose active metabolite inhibits dihydrofolate reductase, decreasing parasite multiplication, and enhances the effect of atovaquone on the mitochondrial membrane potential. 7 Atovaquone-proguanil is generally considered the best tolerated of all antimalarial medications.…”

“…7 Atovaquone-proguanil is generally considered the best tolerated of all antimalarial medications. 6 Product information for atovaquone-proguanil refers to abnormal dreams, anxiety, and depression as possible adverse drug reactions, as well as psychotic events, such as hallucinations, which were identified during postmarketing surveillance of the drug. 8 Reports of elevated mood after administration of the drug, concurrent or not, with the psychotic symptoms, were not found.…”