Alprazolam is relatively more toxic than other benzodiazepines in overdose.
OBJECTIVE
To describe alprazolam poisoning and the relative toxicity of alprazolam compared with other benzodiazepines.


METHODS
A database of consecutive poisoning admissions to a regional toxicology service was searched to identify consecutive benzodiazepine deliberate self poisonings, which were coded as alprazolam, diazepam or other benzodiazepine. Major outcomes used were length of stay (LOS), intensive care (ICU) admission, coma (GCS < 9), flumazenil administration and requirement for mechanical ventilation. Prescription data were obtained for benzodiazepines for the study period.


RESULTS
There were 2063 single benzodiazepine overdose admissions: 131 alprazolam overdoses, 823 diazepam overdoses and 1109 other benzodiazepine overdoses. The median LOS for alprazolam overdoses was 19 h which was 1.27 (95% CI 1.04, 1.54) times longer compared with other benzodiazepines by multiple linear regression. For patients with alprazolam overdoses, 22% were admitted to ICU which was 2.06 (95% CI 1.27, 3.33) times more likely compared with other benzodiazepines after multivariate analysis adjusting for age, dose, gender, time to ingestion and co-ingested drugs. Flumazenil was administered to 14% of alprazolam patients and 16% were ventilated, which was significantly more than for other benzodiazepine overdoses (8% and 11%, respectively). Twelve percent of alprazolam overdoses had a GCS < 9 compared with 10% for other benzodiazepines. From benzodiazepine prescription data, total alprazolam prescriptions in Australia increased from 0.13 million in 1992 to 0.41 million in 2001. Eighty five percent of prescriptions were for panic disorder, anxiety, depression or mixed anxiety/depression.


CONCLUSIONS
Alprazolam was significantly more toxic than other benzodiazepines. The increased prescription of alprazolam to groups with an increased risk of deliberate self poisoning is concerning and needs review.
Isbister
Geoffrey K
GK
Discipline of Clinical Pharmacology, University of Newcastle, Newcastle, Australia. gsbite@ferntree.com
O'Regan
Luke
L
Sibbritt
David
D
Whyte
Ian M
IM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000525:Alprazolam / Q000506:poisoning*; D014151:Anti-Anxiety Agents / Q000506:poisoning*; D001569:Benzodiazepines / Q000506:poisoning*; D003422:Critical Care; D003975:Diazepam / Q000506:poisoning; D062787:Drug Overdose; D006801:Humans; D007902:Length of Stay; D008875:Middle Aged
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D003975:Diazepam; D000525:Alprazolam