Relative toxicity of venlafaxine and serotonin specific reuptake inhibitors in overdose

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 199533(3)199204

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
  1994343159162

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