Minimal Dose for Severe Poisoning and Influencing Factors in Acute Human Clozapine Intoxication

Abstract

Moderate and severe clozapine intoxications can already occur after ingestion of doses in the low therapeutic range, especially in patients older than 50 years. Poisoned patients have to be monitored for central nervous system depression, tachycardia, blood pressure abnormalities, respiratory depression, and QTc prolongation.

Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database

“…These rates are a reason for concern but seem to be consistent with the suggestion that those subjects diagnosed with treatment-resistant schizophrenia, and hence, who are typically being prescribed with clozapine, present with a higher risk of attempted/completed suicide in comparison to the general population [80]. Clozapine overdose may be lethal due to changes in heart rhythm, respiratory depression, and altered state of consciousness [4,81,82]; clozapine high-dosage ingestion may be associated with a mortality rate of approximately 12% [83], with fatalities most typically being associated with cardiac insufficiency and aspiration pneumonia observed with dosages higher than 2 g [45][46][47][48]. Although cases of full recovery after ingestion of either high dosages [46] and/or associated with very high plasma levels (>9000 ng/mL) [45] have been reported, ingestion of 400 mg in a patient not previously treated may be life-threatening [46].…”

Preliminary study of higher‐order language and extralinguistic impairments in individuals with high clinical risk of psychosis and first episode of schizophrenia

“…What is more, expressive language might have been disturbed by difficulty in building up sentence context, resulting in unpredictable speech (Kuperberg et al, 2009). Additionally, expressive language might have also been impaired by the side-effects of medication, or comprehension may have been improved by influence of medication (Kramer, Rauber-Luthy, Kupferschmidt, Krahenbuhl, & Ceschi, 2010;Sestito & Goldberg, 2012). However, these hypotheses require verification in other studies.…”

Metaphor Processing in Schizophrenia Patients: A Study of Comprehension and Explanation of Metaphors

“…In addition, patients' speech could have been dominated by associations between words or by difficulty in building up sentence context, leading to incoherence within and across sentences, and unintelligible and unpredictable speech (Kuperberg, Ditman, Kreher, & Goldberg, 2009), which disturbed the process of metaphor explanation. Additionally, expressive language might have also been impaired by the side-effects of medication, or comprehension may have been improved by influence of medication (Kramer, Rauber-Luthy, Kupferschmidt, Krahenbuhl, & Ceschi, 2010;Sestito & Goldberg, 2012). However, these hypotheses require verification in future studies.…”