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 D 2 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 3Group 2 Risperidone Chlorpromazine Haloperidol Pimozide Trifluoperazine Pericyazine Thioridazine Fluphenazine 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 GroupIncidence of Coma (%) Group1 (trad)7.7 Group 2 (risperidone)4.3 Group 3 (clozapine)13.5

13. Results : Coma VariableOR95 % CI TCAs3.221.6-6.66 Antipsychotic therapy 0.430.22-0.81 Anticonvulsants2.941.5-5.9 Risk factors for all poisonings

14. Results : ICU admission GroupICU admissions (%) 1 (trad)18.8 2 (risperidone)8.7 3 (clozapine)22.1 No significant difference between groups

15. Results : ICU admission VariableOR95 % CI Female sex0.640.41-0.99 Dose1.041.01-1.05 TCAs3.61.9-6.7 Anticonvulsants1.991.1-3.7 Risk factors for all poisonings

16. Results : Ventilation GroupOR95 % CI 1 (trad)-- 2 (risperidone)0.120.01-0.93 3 (clozapine)0.850.39-1.85

17. Results : Ventilation VariableOR95 % CI Dose1.031.01-1.05 Benzodiazepines2.11.4-3.8 TCAs3.71.9-7.4 Anticonvulsants3.01.5-6.0 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