Citalopram toxicity
Authors: Alexander H Glassman
Journal: The Lancet (1997)

Two Lancet letters both interested and concerned me1öström M Eriksson A Thorson J Spigset O Fatal overdose with citalopram.Lancet. 1996; 348: 339-340Summary Full Text Full Text PDF PubMed Scopus (115) Google Scholar, 2Grundemar L Wohlfart B Lagerstedt C Bengtsson F Eklundh G Symptoms and signs of severe citalopram overdose.Lancet. 1997; 349: 1602Summary Full Text Full Text PDF PubMed Scopus (92) Google Scholar (see also M Personne and colleagues Aug 16, p 578).3Personne M Persson H Sjöberg G Citalopram toxicity.Lancet. 1997; 350: 518-519Summary Full Text Full Text PDF PubMed Scopus (68) Google Scholar Taken together they suggest that citalopram, a widely prescribed serotonergic antidepressant, is different from other serotonin selective reuptake inhibitors (SSRIs) and more likely to cause death in overdose. However, I am not convinced that the data support that implication. I think that these two reports remind us that depressed patients should be allowed only limited access to all antidepressant drugs. öström et al1öström M Eriksson A Thorson J Spigset O Fatal overdose with citalopram.Lancet. 1996; 348: 339-340Summary Full Text Full Text PDF PubMed Scopus (115) Google Scholar reported six deaths due to overdose. Only one resulted from citalopram alone, and the patient had taken an astounding 4000 mg–two 100-tablet bottles of citalopram. At the usual daily dose of 20 mg, that is more than a 6-month supply. The overdose and the postmortem plasma concentrations resembled those reported for the only well-documented death from an overdose of fluoxetine taken alone. There is no question that at such doses SSRIs taken alone can be lethal. In all the other five deaths reported by öström, sedative drugs or alcohol had also been taken. Sedative drugs can potentiate the toxicity of all SSRIs.2Grundemar L Wohlfart B Lagerstedt C Bengtsson F Eklundh G Symptoms and signs of severe citalopram overdose.Lancet. 1997; 349: 1602Summary Full Text Full Text PDF PubMed Scopus (92) Google Scholar Again the amounts of drugs ingested were very high. Grundemar et al2Grundemar L Wohlfart B Lagerstedt C Bengtsson F Eklundh G Symptoms and signs of severe citalopram overdose.Lancet. 1997; 349: 1602Summary Full Text Full Text PDF PubMed Scopus (92) Google Scholar reported five cases of citalopram overdose in which the patient survived. Four of the five patients had seizures and the fifth case was amnesic. In all five the QR interval was described as prolonged, but the term was not defined. In addition, it is not clear whether this prolongation was associated with the seizures. What is clear is that in all five Swedish patients the probable dose ingested exceeded any dose seen among 234 cases of fluoxetine overdose collected at one of the four US regional poison control centres,5Borys DK Setzer SC Ling LJ Reisdorf JJ Day LC Krenzelok EP Acute fluoxetine overdose: a report of 234 cases.Am J Emerg Med. 1992; 10: 115-120Summary Full Text PDF PubMed Scopus (107) Google Scholar even though the usual daily dose is the same. A recent Swedish poison control report on citalopram overdose more closely resembles the US experience.3Personne M Persson H Sjöberg G Citalopram toxicity.Lancet. 1997; 350: 518-519Summary Full Text Full Text PDF PubMed Scopus (68) Google Scholar Nevertheless in five of the 44 citalopram-only overdose cases the probable dose was more than 1900 mg, whereas none of 67 US fluoxetine-only overdose patients had ingested more than 1200 mg. Like the cases reported in The Lancet, all five of the patients who had taken more than 1900 mg had seizures. QT abnormalities were not reported, although QRS lengthening without serious arrhythmia did occur. I conclude that as overdoses of SSRIs approach 75 pills, they can be serious, and that the most common serious sign is seizure. To date only two pure SSRI overdose deaths have been reported in the published research and both involved the ingestion of over 200 tablets. However, coingestion is common and readily increases toxicity. Whether citalopram is in any way more toxic is not clear. However, that these citalopram cases were exposed to high doses is clear. Even though SSRIs are much safer in overdose than tricyclic antidepressants, depressed patients attempt suicide and, if enough pills are taken, SSRIs can still be dangerous. The total number of tablets dispensed, even with SSRIs, must remain a concern with potentially suicidal patients.