Suspected clozapine poisoning in the UK/Eire, 1992-2003

OBJECTIVE: Toxicological analyses are often performed to investigate suspected poisoning, but the interpretation of results may not be straightforward. We studied suspected poisoning cases 1992-2003 where blood clozapine and N-desmethylclozapine (norclozapine) were measured in order to assess the relationship of these parameters to outcome. METHODS: Samples were referred from clinicians, pathologists/coroners, or via the Clozaril Patient Monitoring Service (CPMS, Novartis). Information was gathered from clinical, post-mortem, or coroners' reports. RESULTS: There were seven fatal [five male, two female; median (range) age 28 (24-41) year] and five non-fatal [four male, one female; median age 35 (26-41) year] clozapine overdoses. The median post-mortem blood clozapine and norclozapine concentrations were 8.2 (3.7-12) and 1.9 (1.4-2.4)mg/L, respectively [median clozapine:norclozapine ratio 4.4 (2.9-5.1)]. The median plasma clozapine and norclozapine concentrations (first or only sample) were 3.9 (1.7-7.0) and 0.40 (0.30-0.70)mg/L, respectively [median clozapine:norclozapine ratio 7.6 (5.3-18)] in the remainder. These overdoses were in patients who were poorly or non-adherent to clozapine, or who had taken tablets prescribed for someone else. In 54 further people who died whilst receiving clozapine [38 male, 16 female; median age 41 (22-70) year], the median post-mortem blood clozapine and norclozapine concentrations were 1.9 (0-7.7, n = 43) and 1.4 (0-6.0, n = 39)mg/L, respectively [median clozapine:norclozapine ratio 1.5 (0.4-7.6, n = 38)]. The median post-mortem increase in blood clozapine and norclozapine as compared to the most recent ante-mortem measurement was 489 (98-5,350)% and 371 (139-831)%, respectively [median sample time before death 14 (0-30, n = 21) days]. CONCLUSION: Clozapine poisoning cannot be diagnosed on the basis of blood clozapine and norclozapine concentrations alone. The analysis of ante-mortem blood specimens collected originally for white cell count monitoring and the blood clozapine:norclozapine ratio may provide additional interpretative information.     

An Update on the Hazards and Risks of Forensic Anthropology,Part I: Human Remains

This work reviews the hazards and risks of practicing forensic anthropology in North America, with a focus on pathogens encountered through contact with unpreserved human remains. Since the publication of Galloway and Snodgrass' seminal paper concerning the hazards of forensic anthropology, research has provided new information about known pathogen hazards, and regulating authorities have updated recommendations for the recognition and treatment of several infections. Additionally, forensic anthropology has gained popularity, exposing an increased number of students and practitioners to these hazards. Current data suggest many occupational exposures to blood or body fluids go unreported, especially among students, highlighting the need for this discussion. For each pathogen and associated disease, this work addresses important history, reviews routes of exposure, provides an overview of symptoms and treatments, lists decontamination procedures, and presents data on postmortem viability. Personal protection and laboratory guidelines should be established and enforced in conjunction with the consideration of these data.