Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose.
BACKGROUND
Selective serotonin reuptake inhibitors (SSRIs) have increasingly replaced tricyclic antidepressants (TCAs) in the treatment of depression. They appear to be safer in overdose, but there is little information on their spectrum of toxicity in overdose, or relative toxicity of each agent.


OBJECTIVE
To determine the effect of SSRIs in overdose, as a group, and the relative toxicity of five different SSRIs.


METHODS
A review of consecutive SSRI poisoning admissions to a single toxicology unit. Outcomes examined were length of stay [LOS], intensive care [ICU] admission rate, coma, seizures, electrocardiographic [ECG] abnormalities, and presence of serotonin syndrome [SS]. Logistic regression was used to model the outcome QTc >440 msec.


RESULTS
There were 469 SSRI poisoning admissions analyzed after exclusions. The median LOS for all SSRI overdose admissions was 15.3 h (IQR: 10.5-21.3) and 30 of 469 (6.4%; 95% CI 4.3-9.0%) cases were admitted to ICU. The incidence of seizures was 1.9% and coma was 2.4%. Serotonin syndrome occurred in 14% of overdoses. Comparison of median QTc intervals of the five SSRIs was significantly different (p=0.0002); citalopram (450 IQR: 436-484) was individually different to fluoxetine (p=0.045), fluvoxamine (p=0.022), paroxetine (p=0.0002), and sertraline (p=0.001). The proportion of citalopram overdoses with a QTc >440 msec was 68%, differing significantly from sertraline (adjusted OR: 5.11 95% CI 2.32-11.27). Comparison of median QT intervals of the five SSRIs was statistically different (p=0.026); citalopram (400 IQR: 380-440) was individually different from sertraline (p=0.023).


CONCLUSIONS
This study shows SSRIs are relatively safe in overdose despite serotonin syndrome being common. The exception was citalopram, which was significantly associated with QTc prolongation. We believe that cardiac monitoring should be considered in citalopram overdose, particularly with large ingestions and patients with associated cardiac disease.
Isbister
Geoffrey K
GK
Discipline of Clinical Pharmacology, University of Newcastle, Newcastle Mater Misericordiae Hospital, Waratah, New South Wales, Australia. gsbite@ferntree.com
Bowe
Steven J
SJ
Dawson
Andrew
A
Whyte
Ian M
IM
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001315:Australia / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000503:physiopathology; D015331:Cohort Studies; D003128:Coma / Q000139:chemically induced / Q000628:therapy; D003422:Critical Care; D062787:Drug Overdose; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007902:Length of Stay; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000503:physiopathology / Q000628:therapy; D011039:Poison Control Centers; D012640:Seizures / Q000139:chemically induced / Q000628:therapy; D020230:Serotonin Syndrome / Q000503:physiopathology / Q000628:therapy; D017367:Selective Serotonin Reuptake Inhibitors / Q000506:poisoning* / Q000633:toxicity*; D012737:Sex Factors; D016896:Treatment Outcome
D017367:Selective Serotonin Reuptake Inhibitors