Celexa (Citalopram) – A Not So Benign Overdose

So you say you aren’t too impressed with those SSRI overdoses? Well this new drug may just add a little more excitement to your practice. Celexa (citalopram) is one of the newest SSRIs approved by the FDA for major depression. It has been reported to be the most serotonin selective of the SSRIs- however do not let this mislead you to believe that it ONLY acts on serotonin. Citalopram is rapidly absorbed from the GI tract and has peak concentrations within 2 hours. This brings up the proverbial question- should activated charcoal be given more than an hour post ingestion? In most SSRI overdoses, the resultant toxicity is low and we would not bother. However as you continue in your reading, you will find that citalopram may not be quite so benign.

Citalopram has been reported to cause cardiac conduction delays. Animal studies suggested that death is likely due to QTc prolongation with subsequent fatal arrhythmias. The culprit - a cardiotoxic metabolite called didemethyl-citalopram (DDCT). Although some authors believe citalopram to be as safe as other SSRIs in overdose, others believe it to be much more toxic. There have been multiple case reports and case series describing ECG changes after citalopram overdose. These changes include widening of the QRS, nonspecific ST-T changes, bundle branch blocks, ventricular fibrillation, and severe sinus bradycardia. These are especially prominent when the ingestion is greater than 600 mg. Other toxicity noted after overdose include seizures, hypotension, metabolic acidosis, hypokalemia, and syncope. Typically, when the ingestion is less than 600 mg mild symptoms such as nausea, dizziness, diaphoresis, tachycardia, and drowsiness are reported. Recently reported in the literature was a case of a young (21yo) healthy female who developed QTc interval prolongation after ingestion of only 400mg of citalopram. The ECG effects did not occur in this patient until 13 hours post ingestion. The late cardiac effects may be due to the toxic metabolite DDCT which reaches peak concentrations between 6-7 hours and may even be delayed even further in overdose. Further animal literature indicates that citalopram inhibits cardiac Na+ and Ca2+ channels, has class I and IV anti-arrhythmic effects, and may be pro-arrhythmic secondary to intraventricular conduction delays and shortening of repolarization. Citalopram is also known to bind to histamine receptors with the same affinity as clomipramine (an old TCA).

Given all this information, it appears citalopram may not be quite as simple and benign of an overdose as we may have first believed. To put this all into perspective, the normal daily dose of citalopram is 20-40mg a day. Therefore life-threatening toxicity may result with ingestion of only 10 tablets of the 40mg tablets or 20 tablets of the 20mg tablets. Toxicity sounds suspiciously familiar –QRS/QT prolongation, ventricular arrhythmias, Na+ channel blockade, hypotension, metabolic acidosis, seizures…. Sounding similar to a TCA overdose? However, very important differences do exist between the two. First of all TCAs tend to produce tachycardia in overdose whereas citalopram may produce tachycardia or severe bradycardia. Secondly, tricyclic antidepressant toxicity usually occurs very rapidly within 6 hour, and if no symptoms are noted within 6 hours the patient can be discharged. Citalopram overdoses however may not produce ECG changes and seizures until 13 hours later. Therefore these patients should be admitted to a medical intensive care unit for cardiac monitoring and seizure precautions for at least up to 13 hours post ingestion.

Based on the proposed mechanism of cardiovascular toxicity, it would seem logical that sodium bicarbonate may actually be of benefit if cardiovascular abnormalities do occur. Although there is currently no data on whether or not activated charcoal administered after an hour would be of any benefit in decreasing metabolite concentrations, one may wish to consider its use given its pharmacology, the significant toxicity associated with citalopram, and the fairly benign side effect profile of activated charcoal.

References :

1. Pacher P, Ungvari Z, Nanasi P, et al. Speculations on difference between tricyclic and selective serotonin reuptake inhibitor antidepressants on their cardiac effects. Is there any? Current Medicinal Chemistry 1999; 6:469-480.
2. Rasmussen SL, Overo KF, Tanghoj P. Cardiac safety of citalopram: Prospective trials and retrospective analyses. J Clin Psychopharmacology 1999; 19(5):407-415.
3. Grundemar L, Wohlfart B, Lagersteedt C, et al. Symptoms and signs of severe citalopram overdose. Lancet 1997; 349: 1602.
4. Catalano G, Catalano MC, Epstein MA, et al. QTc interval prolongation associated with citalopram overdose: a case report and literature review. Clin Neuropharmacol 2001; May-June: 2-6.
5. Personne M, Sjoberg G, Persson H. Citalopram overdose: review of cases treated in Swedish hospitals. J Toxicol Clin Toxicol 1997; 35: 237-40.

By Kristin Engebretsen, PharmD December 2001
Clinical Toxicology Section - Regions Hospital