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Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose.
J Toxicol Clin Toxicol. 2004; 42(3):277-85.JT

Abstract

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.

Authors+Show Affiliations

Discipline of Clinical Pharmacology, University of Newcastle, Newcastle Mater Misericordiae Hospital, Waratah, New South Wales, Australia. gsbite@ferntree.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15362595

Citation

Isbister, Geoffrey K., et al. "Relative Toxicity of Selective Serotonin Reuptake Inhibitors (SSRIs) in Overdose." Journal of Toxicology. Clinical Toxicology, vol. 42, no. 3, 2004, pp. 277-85.
Isbister GK, Bowe SJ, Dawson A, et al. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol. 2004;42(3):277-85.
Isbister, G. K., Bowe, S. J., Dawson, A., & Whyte, I. M. (2004). Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. Journal of Toxicology. Clinical Toxicology, 42(3), 277-85.
Isbister GK, et al. Relative Toxicity of Selective Serotonin Reuptake Inhibitors (SSRIs) in Overdose. J Toxicol Clin Toxicol. 2004;42(3):277-85. PubMed PMID: 15362595.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. AU - Isbister,Geoffrey K, AU - Bowe,Steven J, AU - Dawson,Andrew, AU - Whyte,Ian M, PY - 2004/9/15/pubmed PY - 2004/9/30/medline PY - 2004/9/15/entrez SP - 277 EP - 85 JF - Journal of toxicology. Clinical toxicology JO - J Toxicol Clin Toxicol VL - 42 IS - 3 N2 - 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. SN - 0731-3810 UR - https://www.unboundmedicine.com/medline/citation/15362595/Relative_toxicity_of_selective_serotonin_reuptake_inhibitors__SSRIs__in_overdose_ L2 - https://core.ac.uk/reader/33206936?utm_source=linkout DB - PRIME DP - Unbound Medicine ER -