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Relative toxicity of venlafaxine and serotonin specific reuptake inhibitors in overdose. Ian Whyte Andrew Dawson. Introduction. Venlafaxine approved for use in Australia on 16th November, 1994 serotonin and noradrenaline reuptake inhibitor (SNRI) case reports of seizures in overdose

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relative toxicity of venlafaxine and serotonin specific reuptake inhibitors in overdose

Relative toxicity of venlafaxine and serotonin specific reuptake inhibitors in overdose

Ian Whyte

Andrew Dawson

introduction
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
objective
Objective
  • To assess the toxicity in overdose of venlafaxine compared with
    • serotonin specific reuptake inhibitors (SSRIs)
    • tricyclic antidepressants (TCAs)
design
Design
  • Cohort study
    • consecutive patients admitted with antidepressant poisoning
  • Hunter Area Toxicology Service (HATS)
study factors
Study factors
  • Age
  • Gender
  • Coingested proconvulsant drugs
  • History of epilepsy and/or anticonvulsant therapy
  • Amount taken
    • Defined Daily Dose
  • Time to presentation
main outcome measures
Main outcome measures
  • Seizures
  • Arrhythmias
  • QRS duration
  • Conscious level
    • Glasgow Coma Score
    • Coma scale
  • Intensive care unit admission
  • Serotonin syndrome
methods
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
cohort
Cohort
  • 3438 DSP admissions between 16/11/1994 and 4/4/2000
  • 889 antidepressant DSPs
subjects
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
dothiepin
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
conclusions
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
conclusions19
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