Symptoms and signs of severe citalopram overdose

Abstract

The general belief is that selective serotonin-reuptake inhibitors (SSRIs) are less toxic than tricyclic antidepressants. Six people who committed suicide and who were found to have high concentrations of venous citalopram after death and Ostrom and colleagues suggests that the deaths result from acute overdose. They suggested both cardiac arrhythmia and generalised seizures as possible causes of death. We report here the findings in five suicide attempts involving non-fatal citalopram overdose. All five patients had acutely and intentionally taken up to 5200 mg of citalopram. Serum concentrations of the parent drug and its metabolite, desmethylcitalopram, were monitored. The highest serum concentrations for citalopram were about 40–350 times higher than those previously observed during therapeutic courses of citalopram at a dose of 20 mg daily. Four patients (a, b, d, e, in table) developed generalised seizures, which were treated with diazepam. One patient (c) admitted to hospital 24 hours after citalopram ingestion had simultaneously taken 375 mg oxazepam and had amnesia for this period. No other drugs were reported to have been taken. Electrocardiographic features included prolonged QT intervals (all patients), sinus tachycardia (a, b, d, e), and inferolateral repolarisation disturbances (b, d, e). The patient with the highest citalopram concentrations (a) developed a hypokalaemia of 1·8 mmol/L. Two patients (a, c) developed rhabdomyolysis (data not shown). On admission, gastric lavage and the administration of activated charcoal were carried out. Electrolyte disturbances were corrected as necessary. Citalopram and its metabolite appeared to have prolonged half lives in those patients in whom repeated samples were taken. Electrocardiographic and biochemical abnormalities gradually returned to normal and all patients recovered without somatic sequelae. Assessment of how concentrations of drugs after death correspond to serum concentrations during life is difficult. Previously reported fatal cases had similar or higher citalopram concentrations (5·2–49 μg/g, roughly corresponding to between 15 000 and 150 000 nmol/L) compared with these non-fatal cases (4240–35 000 nmol/L). The samples reported here were not always taken as peak concentrations. The reported ingested doses seemed similar between the fatal cases and these non-fatal cases (840–3920 mg vs 400–5200 mg), indicating that gastric lavage and active charcoal may have reduced the absorption of citalopram. Both electrocardiographic changes and generalised seizures are characteristic of severe citalopram overdose. Such electrocardiographic changes have been associated with an increased risk of developing dysrhythmia or arrhythmia. Tachycardia and T-wave changes, as well as seizures and metabolic acidosis have been reported in dogs given high doses of citalopram. Generalised seizures have also been reported in human beings as a result of interaction between citalopram and moclobemide. Rhabdomyolysis has been described after imipramine and moclobemide overdose, but, as far as we are aware, not after SSRI overdose. Generalised seizures, metabolic acidosis, hypokalaemia, and electrocardiographic changes after severe citalopram overdose might result in a fatal cardiac arrhythmia. We recommend early gastric lavage, administration of active charcoal, treatment of seizures, and electrocardiographic, biochemical, and toxicological monitoring in the management of such patients.