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

IntroductionPsychotic 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)

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

Methods

Hunter Area Toxicology Service (HATS)

• Regional Centre based at Mater hospital

• Preformatted admission sheet used

• Clinical Database with information on all admissions

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

Antipsychotics

AtypicalsTraditional

Group 1

Group 3 Group 2

Risperidone

ChlorpromazineHaloperidol

PimozideTrifluoperazine

PericyazineThioridazineFluphenazine

ClozapineOlanzapineQuetiapine

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)

Methods

– Drug ingested• amount : defined daily doses (DDDs)• details of coingestants

– Alcohol– Benzodiazepines– Tricyclic antidepressants (TCAs)– Other antidepressants– Anticonvulsants– Paracetamol– Opioid based preparations

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)

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

ResultsBaseline 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

Results :Coma

No statistically significant difference between groups in multivariate analysis

Group Incidence of Coma (%)

Group1 (trad) 7.7

Group 2 (risperidone) 4.3

Group 3 (clozapine) 13.5

Results : Coma

Variable OR 95 % CI

TCAs 3.22 1.6-6.66

Antipsychotic therapy

0.43 0.22-0.81

Anticonvulsants 2.94 1.5-5.9

Risk factors for all poisonings

Results : ICU admission

Group ICU admissions (%)

1 (trad) 18.8

2 (risperidone) 8.7

3 (clozapine) 22.1

No significant difference between groups

Results : ICU admission

Variable OR 95 % CI

Female sex 0.64 0.41-0.99

Dose 1.04 1.01-1.05

TCAs 3.6 1.9-6.7

Anticonvulsants 1.99 1.1-3.7

Risk factors for all poisonings

Results : Ventilation

Group OR 95 % CI

1 (trad) - -

2 (risperidone) 0.12 0.01-0.93

3 (clozapine) 0.85 0.39-1.85

Results : Ventilation

Variable OR 95 % CI

Dose 1.03 1.01-1.05

Benzodiazepines 2.1 1.4-3.8

TCAs 3.7 1.9-7.4

Anticonvulsants 3.0 1.5-6.0

Risk factors for all poisonings

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)

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

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

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

Acknowledgements

• Data extraction– Stuart Allen

• Data entry– Debborah Whyte

– Toni Nash