Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants.
BACKGROUND
Selective serotonin reuptake inhibitors (SSRIs) and venlafaxine have been regarded as less toxic in overdose than tricyclic antidepressants (TCAs). Within the TCAs, dothiepin has greater toxicity. Venlafaxine may be more toxic than SSRIs.


OBJECTIVE
To assess the toxicity in overdose of venlafaxine and SSRIs compared to TCAs, and of dothiepin compared to other TCAs.


METHODS
Cohort study of prospectively collected data from the Hunter area, NSW, Australia.


METHODS
First admissions with antidepressant deliberate self-poisoning (DSP) (November 1994 to April 2000) were identified; the presence of seizures, life-threatening arrhythmias, coma, serotonin toxicity or ICU admission, and QRS duration were noted.


RESULTS
There were 538 admissions, with no deaths. The odds ratio (OR) for seizures with dothiepin vs. other TCAs was 3.4 (95%CI 1.2-9.9). Seizures occurred in 7/51 (14%) venlafaxine overdoses; all patients with seizures consumed > or =900 mg. The OR for seizures vs. TCAs was 4.4 (95%CI 1.4-13.8). Coma was less likely with venlafaxine and SSRIs. SSRIs, but not venlafaxine, were less likely to prolong the QRS to > or =100 ms. ICU admission was less likely for SSRIs. Serotonin toxicity was much more common with venlafaxine and SSRIs.


CONCLUSIONS
Venlafaxine and dothiepin are pro-convulsant in overdose. Venlafaxine is more likely to cause serotonin toxicity, but less likely to cause coma than TCAs. SSRIs are less likely to cause coma, require ICU admission, or prolong the QRS, but are more likely to cause serotonin toxicity. Antidepressants other than TCAs or venlafaxine should be considered in patients at risk of seizure or suicide.
Whyte
I M
IM
School of Population Health Sciences, Faculty of Medicine and Health Sciences, University of Newcastle, and Department of Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital, NSW, Australia. mdimw@cc.newcastle.edu.au
Dawson
A H
AH
Buckley
N A
NA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000929:Antidepressive Agents, Tricyclic / Q000506:poisoning*; D015331:Cohort Studies; D003511:Cyclohexanols / Q000506:poisoning*; D004308:Dothiepin / Q000506:poisoning*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D017367:Selective Serotonin Reuptake Inhibitors / Q000506:poisoning*; D000069470:Venlafaxine Hydrochloride
D000929:Antidepressive Agents, Tricyclic; D003511:Cyclohexanols; D004308:Dothiepin; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride