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

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. 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. 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 (98–5350)% and 371 (139–831)%, respectively [median sample time before death 14 (0–30, n = 21) days]. 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.