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Alprazolam is relatively more toxic than other benzodiazepines in overdose

  1. Geoffrey K. Isbister1,2,*,
  2. Luke O'Regan1,
  3. David Sibbritt3,
  4. Ian M. Whyte1,4

Article first published online: 21 APR 2004

DOI: 10.1111/j.1365-2125.2004.02089.x

Issue

British Journal of Clinical Pharmacology

British Journal of Clinical Pharmacology

Volume 58, Issue 1, pages 88–95, July 2004

Additional Information

How to Cite

Isbister, G. K., O'Regan, L., Sibbritt, D. and Whyte, I. M. (2004), Alprazolam is relatively more toxic than other benzodiazepines in overdose. British Journal of Clinical Pharmacology, 58: 88–95. doi: 10.1111/j.1365-2125.2004.02089.x

Author Information

  1. 1

    Discipline of Clinical Pharmacology, University of Newcastle, Newcastle, Australia;

  2. 2

    Emergency Department, Newcastle Mater Hospital, Newcastle, Australia;

  3. 3

    School of Medical Practice and Population Health, University of Newcastle, Newcastle, Australia and

  4. 4

    Department of Clinical Toxicology & Pharmacology, Newcastle Mater Hospital, Newcastle, Australia

*Dr Geoffrey K. Isbister, Emergency Department, Newcastle Mater Hospital, Edith St, Waratah NSW 2298, Australia. Tel: + 61 (0) 2 4921 1211 Fax: + 61 (0) 2 4960 2088 E-mail: gsbite@ferntree.com

Publication History

  1. Issue published online: 4 JUN 2004
  2. Article first published online: 21 APR 2004
  3. Received 20 October 2003 Accepted 11 December 2003

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Keywords:

  • alprazolam;
  • benzodiazepines;
  • overdose;
  • toxicity

Aims

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.

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