Relative toxicity of benzodiazepines in overdose

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Abstract
Objective: To assess the sedative effects in overdose of temazepam and oxazepam compared with other benzodiazepines to determine if this explains reported differences in fatal toxicity Design: Cohort study of patients admitted with benzodiazepine poisoning Setting: Newcastle, Australia Subjects: 303 patients who had ingested benzodiazepine alone or in combination with alcohol and presented to a general hospital which served a well defined geographical area Main outcome measures: Degree of sedation: Glasgow coma score, McCarron Score, and whether patients were stuporose or comatose Results: Oxazepam produced less and temazepam more sedation than other benzodiazepines. Unadjusted odds ratios for coma with oxazepam and temazepam compared with other benzodiazepines were 0.0 (95% confidence interval 0.0 to 0.85) and 1.86 (0.68 to 4.77) respectively, x2=7.08, 2df, P=0.03. After adjustment for potentially confounding effects of age, dose ingested, and coingestion of alcohol, the odds ratios were 0.22 (0.0 to 1.43) for oxazepam and 1.94 (0.57 to 6.23) for temazepam. Similar results were obtained for other measures of sedation Conclusions: These results were in accordance with fatal toxicity indices derived from coroners' data on mortality and rates of prescription. The relative safety of benzodiazepines in overdose should be a consideration when they are prescribed Key messages In a recent study of coronial data large differences were noted in the number of fatal poisonings caused by different benzodiazepines (after correction for market share) This study provides evidence that there are differences, both before and after adjustment for a number of potential confounders, between benzodiazepines in the incidence with which they cause major sedation in overdose These clinical differences provide explanation and support for the coronial data Benzodiazepines cannot be assumed to be safe in patients at risk of self poisoning, but some benzodiazepines seem to be safer than others