Predictive factors for generalized seizures after deliberate citalopram overdose

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Citalopram is a common means of self‐poisoning in young adults. • Generalized seizures are a recognised complication after selective serotonin reuptake inhibitor overdose (including citalopram overdose). WHAT THIS STUDY ADDS • The minimum stated citalopram dose associated with seizures in the absence of co‐ingested drugs was 400 mg. • Co‐ingestion of a tricyclic antidepressant or venlafaxine confers a 15‐fold increased risk of seizures. AIMS Seizures are a recognized complication of citalopram overdose. The present study sought to establish risk factors for seizures in this high‐risk patient group, including stated dose ingested, co‐ingested drugs or ethanol, and electrolyte disturbances. METHODS A retrospective casenote review was carried out of patients who attended the Emergency Department due to citalopram overdose between January 2000 and July 2007 inclusive. Stepwise logistic regression analysis considered age, gender, stated citalopram dose, acute ethanol consumption, co‐ingested drugs, administration of activated charcoal, and hyponatraemia. RESULTS There were 241 patients (177 women), and the median (interquartile range) stated citalopram dose was 300 mg (200 to 600 mg). Generalized seizures occurred in 18 patients (7.5%). Logistic regression analysis found co‐ingested tricyclic antidepressants or venlafaxine predicted seizures with odds ratio = 15 (95% confidence interval 3, 75). In the absence of co‐ingested drugs, the minimum citalopram dose associated with seizures was 400 mg. Odds ratio for seizures = 1.1 (95% confidence interval 1.0, 1.2) for every 100 mg increment in citalopram dose. Seizures were associated with a greater need for invasive ventilatory support, higher creatine kinase activity, and prolonged hospital stay. CONCLUSIONS Generalized seizures are an important manifestation of citalopram toxicity, and cannot be explained solely by electrolyte disturbances or co‐ingestion of other drugs or ethanol. The strongest predictors of seizures in this patient series were ingestion of high citalopram dosages and co‐ingestion of drugs capable of lowering seizure threshold.

Evaluation of a QT nomogram for risk assessment after antidepressant overdose

“…Data were available for 858 ECG recordings that were taken from 541 patients with median (IQR) age 34 years (25-42 years), including 161 men (29.8%).The median stated dose ingested, as a multiple of the defined daily dose was similar between groups: citalopram 16 (10-30), mirtazapine 15 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), and venlafaxine 15 (9-28). None of the patients studied developed torsade de pointes or other significant arrhythmia.…”

Treatment of acute and remote symptomatic seizures

“…Psychiatric medications cause seizures most often in overdose situations, but some, such as clozapine, maprotiline, and short-acting bupropion, lower the seizure threshold in therapeutic doses [29][30][31].…”

Clinical use of antidepressant therapy and associated cardiovascular risk

“…Both citalopram and escitalopram are capable of provoking generalized seizures 40,41. Citalopram and escitalopram are known to cause dose-dependent QT prolongation, although the mechanism remains uncertain and may be unrelated to serotonin reuptake per se 1,2.…”