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].


CONCLUSIONS
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.
Flanagan
R J
RJ
Medical Toxicology Unit, Guy's and St Thomas' NHS Foundation Trust, Avonley Road, London SE14 5ER, UK. robert.flanagan@gstt.nhs.uk
Spencer
E P
EP
Morgan
P E
PE
Barnes
T R E
TR
Dunk
L
L
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000097:blood / Q000506:poisoning*; D003024:Clozapine / Q000031:analogs & derivatives* / Q000097:blood / Q000506:poisoning*; D062787:Drug Overdose; D005260:Female; D005554:Forensic Medicine; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011041:Poisoning / Q000175:diagnosis; D011180:Postmortem Changes; D013405:Suicide; D016312:Treatment Refusal; D006113:United Kingdom
D014150:Antipsychotic Agents; C058272:norclozapine; D003024:Clozapine