1. Relative toxicity of venlafaxine and serotonin specific reuptake inhibitors in overdose Ian Whyte Andrew Dawson

2. Introduction • Venlafaxine • approved for use in Australia on 16th November, 1994 • serotonin and noradrenaline reuptake inhibitor (SNRI) • case reports of seizures in overdose • ADRAC reports of seizures in therapeutic use • increasing use

3. Objective • To assess the toxicity in overdose of venlafaxine compared with • serotonin specific reuptake inhibitors (SSRIs) • tricyclic antidepressants (TCAs)

4. Design • Cohort study • consecutive patients admitted with antidepressant poisoning • Hunter Area Toxicology Service (HATS)

5. Study factors • Age • Gender • Coingested proconvulsant drugs • History of epilepsy and/or anticonvulsant therapy • Amount taken • Defined Daily Dose • Time to presentation

6. Main outcome measures • Seizures • Arrhythmias • QRS duration • Conscious level • Glasgow Coma Score • Coma scale • Intensive care unit admission • Serotonin syndrome

7. Methods • HATS database • Admissions with antidepressant deliberate self-poisoning (DSP) • Excluded coingestion • thioridazine • Buckley NA, Whyte IM, Dawson AH. Cardiotoxicity more common in thioridazine overdose than with other neuroleptics. Journal of Toxicology - Clinical Toxicology 1995;33(3):199–204

8. Cohort • 3438 DSP admissions between 16/11/1994 and 4/4/2000 • 889 antidepressant DSPs

9. Subjects • Excluded • moclobemide, nefazodone, mianserin • second and subsequent admissions • coingested antidepressants • 82 dothiepin • 456 first admissions of a single antidepressant • 172 TCA (excluding dothiepin) • 233 SSRI • 51 venlafaxine

10. Dothiepin • 9 of 82 (11%) dothiepin overdoses had a seizure • 6 of 172 (3.5%) other TCA overdoses seized • Odds ratio (95% CI) • 3.4 (1.2 – 9.9) • Buckley NA, Dawson AH, Whyte IM, Henry DA. Greater toxicity in overdose of dothiepin than of other tricyclic antidepressants. Lancet 1994;343:159–162

11. Market share

12. Study factors

13. Outcomes (1)

14. Outcomes (2)

15. Venlafaxine vs TCAs

16. SSRIs vs TCAs

17. Seizures

18. Conclusions • Dothiepin in overdose • compared to other TCAs • is proconvulsant • Venlafaxine in overdose • compared to other TCAs • is proconvulsant • more likely to cause serotonin toxicity • less likely to cause coma

19. Conclusions • SSRIs in overdose • compared to other TCAs • less likely to cause coma • less likely to require ICU admission • less likely to prolong the QRS • more likely to cause serotonin toxicity • Antidepressants other than dothiepin or venlafaxine should be considered in patients at risk of seizures or suicide