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Relative toxicity of traditional versus atypical antipsychotics in deliberate self poisoning

Relative toxicity of traditional versus atypical antipsychotics in deliberate self poisoning. M A Downes, G K Isbister, D Sibbritt, I M Whyte, A H Dawson. Introduction. Psychotic disease Treated with D 2 receptor blocking agents Phenothiazines/Butyrophenones

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Relative toxicity of traditional versus atypical antipsychotics in deliberate self poisoning

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  1. Relative toxicity of traditional versus atypical antipsychotics in deliberate self poisoning M A Downes, G K Isbister, D Sibbritt, I M Whyte, A H Dawson

  2. Introduction Psychotic disease • Treated with D2 receptor blocking agents • Phenothiazines/Butyrophenones • Efficacious in treating positive symptoms BUT • Extrapyramidal adverse effects • Less efficacious for negative symptoms Atypical agents • Less EPS • Better for negative symptoms • Refractory disease (clozapine)

  3. Objective • To compare the overdose profile of the atypical antipsychotics with the traditional antipsychotics • Are olanzapine/quetiapine/clozapine more sedative ? • Is risperidone less toxic ? • Examine factors predicting complications in whole population

  4. Methods Hunter Area Toxicology Service (HATS) • Regional Centre based at Mater hospital • Preformatted admission sheet used • Clinical Database with information on all admissions

  5. Methods • Inclusion/Exclusion criteria • All oral, deliberate self poisonings with antipsychotics from 13/01/87 to 25/11/03 • Could ingest • more than 1 drug BUT • not more than 1 antipsychotic • First admission only included • amisulpiride ingestions excluded

  6. Antipsychotics Atypicals Traditional Group 1 Group 3 Group 2 Chlorpromazine Haloperidol Pimozide Trifluoperazine Pericyazine Thioridazine Fluphenazine Risperidone Clozapine Olanzapine Quetiapine

  7. Methods • Data collected • Demographics • sex, age • Therapeutic use of antipsychotics • Clinical data • Coma as defined by GCS < 9 • Need for ICU admission • need for mechanical ventilation • Length of stay (hours)

  8. Methods • Drug ingested • amount : defined daily doses (DDDs) • details of coingestants • Alcohol • Benzodiazepines • Tricyclic antidepressants (TCAs) • Other antidepressants • Anticonvulsants • Paracetamol • Opioid based preparations

  9. Methods • Statistical Analysis • Descriptive statistics • Proportions for dichotomous variables • Means for continuous variables • Outcomes • Odds ratios (OR) with 95 % confidence intervals (CIs) • Correlation coefficients and 95 % CIs • Logistic and linear regression models (STATA 8)

  10. Results 13/01/87 - 25/11/03 • 1218 antipsychotic overdoses • Excluded • 85 as > 1 antipsychotic ingested • 1 excluded due to use of Amisulpiride • 1132 admissions of which 668 were first admissions

  11. Results Baseline Characteristics • 43 % male • Mean age 32.7 ( SD 12.3) • 495 (74 %) Group 1 • 173 (26 %) atypical cases • 69 (10.3 %) Group 2 • 104 (15.7 %) Group 3 • 262 (39 %) no coingestants • 408 (61 %) coingested alcohol/other drugs

  12. Results :Coma No statistically significant difference between groups in multivariate analysis

  13. Results : Coma Risk factors for all poisonings

  14. Results : ICU admission No significant difference between groups

  15. Results : ICU admission Risk factors for all poisonings

  16. Results : Ventilation

  17. Results : Ventilation Risk factors for all poisonings

  18. Results : Length of stay • Group 2 (risperidone) v Group 1 (trad) • LOS 0.75 less for group 2 (95 % CI : 0.6-0.94) • Group 3 (clozapine) v Group 1 (trad) • No significant difference • Whole population risk factors for increased LOS •  Age (10 year increment) •  Dose (10 DDDs)

  19. Discussion • Risperidone is less toxic in overdose • No difference in ICU admission rate or incidence of coma BUT • need for ventilation less • Shorter length of stay • No differences demonstrated for • Clozapine/Olanzapine/Quetiapine

  20. Discussion • Predictors of complications in whole population • Coingesting TCAs or anticonvulsants increases incidence of • Coma • ICU admission • Ventilation • ↑ Dose ingested increases • ICU admission rate • Ventilation rate • length of stay

  21. Discussion • ↑ age • Led to increased length of stay • Therapeutic use of antipsychotics • Protective effect against coma Limitations : • Retrospective study, though data collected prospectively • Drug levels not obtained

  22. Acknowledgements • Data extraction • Stuart Allen • Data entry • Debborah Whyte • Toni Nash

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