Citalopram Overdose Research Articles

Comparison of clinicodemographic characteristics in patients with selective serotonin reuptake inhibitors poisoning: A cross-sectional study.

Our objective of this study was to evaluate patients of Selective Serotonin Reuptake Inhibitors (SSRIs) overdose and compare the toxicological effects of citalopram overdose with other SSRIs in adult poisoning cases. This cross-sectional study focused on acute, known-type SSRI ingestions. Demographic and toxicological data were collected on the patients. The outcomes analyzed were length of hospital stay, coma, seizures, electrocardiographic abnormalities, abnormal heart examination, and the presence of serotonin syndrome. There were a total of 199 cases, with 165 (82.9%) being women. The majority of cases (n=76, 38.2%) were attributed to citalopram, followed by sertraline (n=67, 33.7%), fluoxetine (n=33, 16.6%), fluvoxamine (n=10, 5%), escitalopram (n=6, 3%), paroxetine (n=1, 0.5%), and mixed (n=6, 3%). The most common symptoms were nausea and vomiting (n=96, 48.2%). Most patients (58.3%) were conscious, with only 7 patients (3.5%) experiencing seizures. Among those with seizures, six patients had taken citalopram, with 50% of them ingesting 400mg of citalopram. Tachycardia was observed in 62 (31.2%) patients, while no QT interval prolongation, PR interval changes, or arrhythmias were reported. Serotonin toxicity was noted in only 6 patients (3%), with 4 of them being poisoned with citalopram. The incidence of seizures with citalopram was significantly higher than with other SSRIs (odds ratio (OR)=10.457; 1.6-2.88, P=0.008), while nausea and vomiting were significantly more common in poisoning cases involving other SSRIs (OR=0.51; 0.2-0.9, P=0.02). There were no reported deaths. Ingesting SSRIs results in minimal toxicity. However, seizures are more likely to occur with citalopram compared to other SSRIs.

ARDS IN THE SETTING OF SEROTONIN SYNDROME

ARDS IN THE SETTING OF SEROTONIN SYNDROME

Citalopram Overdose Leading to Cardiac Instability and Late-Onset Severe Serotonin Syndrome

Citalopram Overdose Leading to Cardiac Instability and Late-Onset Severe Serotonin Syndrome

Acute respiratory distress syndrome, metabolic acidosis, and respiratory acidosis associated with citalopram overdose

Acute respiratory distress syndrome, metabolic acidosis, and respiratory acidosis associated with citalopram overdose

Acute respiratory distress syndrome, metabolic acidosis, and respiratory acidosis associated with citalopram overdose

We report a 53-year-old man who ingested 2400 mg of citalopram and presented to the emergency department three hours post-ingestion with altered mental status, somnolence, and a blood pressure of 67/45 mmHg. He failed to respond to three boluses of normal saline (1000 ml each) and required vasopressors. The patient developed serotonin syndrome with hyper-reflexia, rigidity, and ankle myoclonus. He had a tonic-clonic seizure in the ER requiring intravenous lorazepam and phenytoin. An ECG showed QT prolongation. Chest x-ray on presentation was normal. Within 32 hours the patient developed acute respiratory distress, hypoxemia, a wide A-a gradient, PaO2/FiO2< 200, and chest x-ray changes compatible with acute respiratory distress syndrome (ARDS). He had normal central venous pressures, normal cardiac biomarkers, normal systolic and diastolic functions on echocardiography, and no acute ST/T wave changes. His ABG showed a metabolic acidosis and a respiratory acidosis. The patient required intubation and ventilation. Citalopram has been associated with seizures and ECG abnormalities after overdoses. The respiratory complications and metabolic acidosis have been reported only a few times in the literature. We are reporting the second case of ARDS and the fifth case of metabolic acidosis due to citalopram overdose and suggest that the metabolic acidemia is explained by propionic acid. The respiratory acidosis seen in this patient has not been reported previously.

Sodium Channel Blockade With QRS Widening After an Escitalopram Overdose

Escitalopram is rarely associated with prolongation of the QTc interval; however, there are no reported cases of QRS complex widening associated with escitalopram overdose. We report a case of a patient who presented with both QRS complex widening and QTc interval prolongation after an escitalopram overdose. A 16-year-old girl presented to the emergency department after ingestion of escitalopram, tramadol/acetaminophen, and hydrocodone/acetaminophen. Laboratory results were significant for 4-hour acetaminophen 21.1 μg/mL. Serum electrolytes including potassium, magnesium, and calcium were all normal. Initial electrocardiogram (ECG) revealed a widened QRS with an incomplete right bundle branch pattern. After administration of 100-mEq sodium bicarbonate, a repeat ECG revealed narrowing of the QRS complex and a prolonged QTc interval. Magnesium sulfate 2 g intravenous and sodium bicarbonate drip were initiated. A repeat ECG, 1 hour after the second, revealed normalization of the QRS complex and QTc interval. Prolongation of the QTc interval is an expected effect of escitalopram. Both escitalopram and citalopram are metabolized to the cardiotoxic metabolite S-didesmethylcitalopram and didesmethylcitalopram, respectively, which have been implicated in numerous cardiac abnormalities including widening of the QRS complex. Although never previously described with escitalopram, this mechanism provides a reasonable explanation for the QRS complex widening and incomplete right bundle branch block that occurred in our patient. Both QRS complex widening and QTc interval prolongation should be monitored in cases of escitalopram and citalopram overdoses.

Escitalopram and QTc prolongation

One should not conclude from the discussion by Lam1 that escitalopram is free of cardiac risks. Citalopram and escitalopram differ marginally in terms of their risk of prolonging the QTc interval sufficient to link to torsade de pointes (TdP). Citalopram and escitalopram each demonstrate a dose-dependent QTc prolongation.1 Although the magnitude of QTc prolongation appears to be greater for citalopram than escitalopram, the dose–QTc correlation is similar for both drugs. While the U.S. Food and Drug Administration and Health Canada issued warnings only for citalopram, the Medicines and Healthcare Products Regulatory Agency in the United Kingdom issued safety warnings for both citalopram and escitalopram.2 The threshold for clinical significance of the QTc interval is an absolute duration of 500 ms or longer or a change from baseline of 60 ms or more.3 The warnings did not specify whether any participants enrolled in the thorough QTc studies exceeded these thresholds for either drug. About 500 escitalopram overdoses and nearly 600 citalopram overdoses have been described, without serious cardiac sequelae or deaths due to either drug.4 Less than one-third of patients with citalopram overdoses presented with QTc interval prolongation. In 1 study, 14% of patients with escitalopram overdoses presented with QTc interval prolongation. In another study, the proportion of prolonged QTc intervals associated with escitalopram overdoses (1.7%) was not significantly different from that associated with citalopram overdoses (3.7%). These studies preclude a definitive assessment of the relative cardiotoxicity of citalopram versus escitalopram, but they do not demonstrate clinically meaningful differences in cardiotoxic effects. The mechanisms underlying drug-associated QTc interval prolongation are not well understood. Drug dosage is only 1 of several factors that increase the risk of QTc interval prolongation. In this regard it is notable that fewer than one-third of overdoses with citalopram or escitalopram are associated with QTc prolongation. If dose were a major factor with these drugs, you might expect that most overdoses would be associated with QTc prolongation. In our review,5 QTc interval prolongation or TdP due to citalopram occurred in the setting of citalopram overdose and/or in the presence of well-established risk factors, including advanced age, existing cardiac illness, multiple medical illnesses, electrolyte disturbances (hypokalemia, hypomagnesaemia) and concomitant use of QTc-prolonging drugs. These and other risk factors (baseline prolonged QTc, metabolic inhibition from other drugs, and hepatic impairment) have been emphasized in the regulatory warnings and would be particularly important for drugs like citalopram and escitalopram that prolong QTc interval marginally. Physicians should be mindful of these risk factors when prescribing these medications.

Citalopram and cardiac toxicity

Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant that is widely used in clinical practice. Recent data have indicated that high therapeutic citalopram doses may cause electrocardiographic abnormalities, and the regulatory authorities have amended its licenced dosage. The present manuscript reviews the available data concerning citalopram and cardiac toxicity. Published data concerning the cardiac effects of citalopram were ascertained, and clinical data were considered separately between adverse effects arising from therapeutic use versus toxicity in the setting of intentional overdose. The occurrence of electrocardiographic abnormalities has long been recognised as a complication of acute citalopram overdose; a dose-effect relationship for QT prolongation has been described in a number of large case series, including several cases of torsades de pointes. In contrast, few data indicate the occurrence of QT prolongation and arrhythmia after therapeutic doses, and a dose-effect relationship within the therapeutic range has only recently been established. Citalopram is more likely to cause QT prolongation in patients with metabolic disturbance or pre-existing cardiac disease. A dose-effect relationship for QT prolongation exists across a broad range of citalopram doses, such that caution must be exercised when prescribing high doses or if there are co-existent risk factors for QT effects. The available data illustrate how clinical toxicity data may offer an earlier signal of cardiac effects than ascertained from conventional pharmacovigilance methods.

Mechanisms of high-dose citalopram-induced death in a rat model

Citalopram, a selective serotonin reuptake inhibitor, is generally considered to be of low toxicity. However, serotonin syndrome, seizures, electrocardiographic abnormalities as well as respiratory failure and death have been described in patients with citalopram overdose. The mechanisms of severe toxicity remain unclear. Our objective was to study the mechanisms of death following high-dose citalopram administration in Sprague Dawley rats. The median lethal dose (MLD) of intraperitoneal (i.p.) citalopram was measured using Dixon & Bruce's up-and-down method at 102mg/kg. Dose–effect relationships of citalopram-induced clinical features, alterations in arterial blood gas and plethysmography, and disturbances in blood lactate, plasma and platelet serotonin concentrations were studied. Seizures were significantly increased in rats receiving 80% and 120% of citalopram MLD versus controls (p<0.05 and p<0.01, respectively). A significant decrease in body temperature was observed after 90min in rats treated with doses >60% MLD in comparison to controls (p<0.05). The occurrence of serotonin behavioural syndrome was comparable in all groups. Citalopram administration did not result in significant hypoxemia, hypercapnia and lactate elevation. However, a significant moderate increase in the inspiratory time (p<0.05) accompanied with an expiratory braking was observed. A significant dose-related linear decrease in platelet serotonin and increase in plasma serotonin concentrations were measured (p<0.05). Pre-treatments of rats receiving 120% of citalopram MLD with diazepam (1.77mg/kg) and cyproheptadine (17.1mg/kg) prevented seizures and death, but propranolol pre-treatment was ineffective. Neuroprotection with diazepam and cyproheptadine was not associated with decreased serotonin plasma concentrations. In conclusion, citalopram-induced deaths resulted from seizures in relation to serotonin release, whilst respiratory and metabolic toxicity was mild. Our observations support the role of serotonin-induced neurotoxicity in citalopram overdose and suggest that cyproheptadine and benzodiazepines, but not beta-blockers, may have a role in the management of citalopram toxicity.

Delayed, Fatal Cardiotoxicity Associated With Bupropion and Citalopram Overdose

Delayed, Fatal Cardiotoxicity Associated With Bupropion and Citalopram Overdose

5-HT3 receptor mediates the dose-dependent effects of citalopram on pentylenetetrazole-induced clonic seizure in mice: Involvement of nitric oxide

Citalopram is a selective serotonin reuptake inhibitor (SSRI), widely used in the treatment of depressive disorders. It has been shown that citalopram affects seizure susceptibility. Although the exact mechanism of these effects are not yet fully understood, recent data suggest that 5HT(3) receptors and nitric oxide (NO) might participate in the central effects of SSRIs. In this study in a mouse model of clonic seizure induced by pentylenetetrazole we investigated whether 5-HT(3) receptors are involved in the effects of citalopram on seizure threshold. In our experiments, citalopram at lower doses (0.5 and 1mg/kg, i.p) significantly increased the seizure threshold and at higher doses (≥25mg/kg) showed proconvulsive effects. Moreover, mCPBG (a 5-HT(3) receptor agonist) at low and non-effective doses augmented while non-effective doses of tropisetron prevented the anticonvulsive properties of citalopram. On the other hand, Low doses of nitric oxide synthase inhibitors l-NAME and 7-NI alone or in combination with lower doses of 5-HT(3) receptor agonist enhanced the anticonvulsive property of citalopram, while l-arginine (NO precursor) alone or in combination with tropisetron blocked the protective effect of citalopram. In summary, our findings demonstrate that 5-HT(3) receptor mediates the anticonvulsant properties of low doses of citalopram, whereas it seems that the proconvulsive effect is mostly mediated through the NO pathway and can be totally blocked by NOS inhibitors. This could propose a new approach toward finding the mechanism of citalopram activity, curtailing the adverse effects of citalopram and perhaps managing the convulsions as a vicious consequence of citalopram overdose.

A Critical Evaluation of the Cardiac Toxicity of Citalopram: Part 1

In August 2011, the U.S. Food and Drug Administration issued a safety announcement that the antidepressant drug citalopram (Celexa(®)) should not be used at dosages greater than 40 mg per day (or greater than 20 mg per day for patients 60 and older) because it can cause abnormal changes in the electrical activity of the heart. This warning was based on the results of a "thorough QT/QTc study" of citalopram and on post-marketing reports of QT prolongation and torsade de pointes in some patients taking the drug. The statistically significant results from the "thorough QT/QTc study" were small in magnitude, and their clinical significance is questionable. Additional electrocardiogram analyses from other studies do not confirm these findings. Nearly 600 cases of citalopram overdoses have been described. Although citalopram overdose is not entirely "cardiac safe," only a proportion of patients develop QTc prolongation without serious cardiac sequelae and no deaths. Three studies comparing citalopram overdoses to other antidepressant overdoses do not demonstrate clinically meaningful differences in cardiotoxic effects.

Drug monitoring of a case of citalopram overdosage

Selective serotonin reuptake inhibitors are widely prescribed drugs without recognized cardiovascular risk. We report the case of a 54-year-old patient who developed QTc interval prolongation, followed by ventricular fibrillation episodes, 10 hours after admission to the ICU, in the setting of a citalopram overdose. Citalopram plasma values dropped from 5.88 to 0.34 mg/L at 9 days postadmission. The patient was treated by oral activated charcoal, and final outcome was favorable.

Citalopram-Induced Seizures in a Healthy Adult Taking an FDA-Approved Dosage

To the Editor: A retrospective review of published literature disclosed case reports of seizures following citalopram overdose.1 We present a case of citalopram-induced seizures in an otherwise healthy woman taking a US Food and Drug Administration (FDA)–approved dosage. Case report. Ms A, a 50-year-old African American woman, had a past psychiatric history significant for major depressive disorder, no comorbid medical history, and no previously documented seizure disorder. She presented to the emergency department in October 2010 after 2 witnessed generalized tonic-clonic seizures, lasting 2 minutes each, on 2 consecutive days. She was confused upon presentation to the emergency department. Citalopram 20 mg po daily had been started 4 days prior to the first seizure. She had taken sertraline 50 mg po daily for a year, but had stopped taking that drug several years previously after depression did not improve. At the time of presentation, she had been taking gabapentin 300 mg po daily for Morton's neuroma. Past medical and surgical histories were not significant for any major illness. Family history was negative for seizure disorder, stroke, or myocardial infarct. She was an employed single mother of 6 children. She smoked half a pack of cigarettes daily, but there was no history of alcohol or illegal drug use. Physical and neurologic examinations revealed no abnormalities. Ms A was admitted to the general medical floor for observation, which lasted for 4 days. Complete blood cell count, comprehensive metabolic panel findings, thyroid-stimulating hormone level, alcohol level, and urine drug screen findings were within normal limits. Findings of cranial computed tomography and magnetic resonance imaging, with and without contrast, were within normal limits. Electroencephalogram (EEG) also revealed no abnormalities, and no evidence of an epileptic focus was found. Upon Ms A's admission to the medical unit, citalopram was stopped; there were no further seizures during her stay in the hospital or in 1 month of follow-up. To the best of our knowledge, there is no published case of seizures associated with short-term use of citalopram within the FDA-approved dosage range of 20 to 40 mg/d2 in healthy adults. We were unable to identify any other cause of the seizures. Prolonged previous uneventful use of sertraline ruled out a general reaction to the selective serotonin reuptake inhibitor (SSRI) class. Citalopram evokes spontaneous EEG spikes in normal rats, and reduces paired-pulse inhibition in both normal and epileptic rats.3 To the best of our knowledge, this is the first report to document that citalopram may induce seizures at low doses, even in a patient who had tolerated another SSRI in the past. If practitioners recognize this association, expensive investigations and extensive hospital stays may be prevented, although prudent practice would very likely still require the type of investigations undertaken with our patient.

Evaluation of a QT nomogram for risk assessment after antidepressant overdose

A QT-heart rate nomogram has recently been proposed as a means of identifying patients at risk of torsades de pointes after antidepressant overdose, based on published cases of drug-induced torsades de pointes. The present study sought to examine the performance of the nomogram in patients who ingest an antidepressant overdose but do not develop arrhythmia. A retrospective case control study of patients presenting to hospital after overdose of citalopram, mirtazapine and venlafaxine was carried out. The primary outcome variable was QT higher than the nomogram, and was compared with occurrence of QT(c) (QT corrected by Bazett's formula) greater than ≥440 ms and QT(c) ≥500 ms, with comparison between drugs. Data are expressed as proportions in each group with 95% confidence intervals. There were 858 electrocardiograms from 541 patients. QT was higher than the nomogram in 2.4% (1.4, 4.1%), whereas QT(c) was ≥440 ms in 23.1% (95% CI 19.8, 26.8%), and QT(c) was ≥500 ms in 1.1% (0.5, 2.5%). Citalopram overdose was more likely to be associated with QT higher than the nomogram compared with the other agents (difference 7.0%, 95% CI 2.9, 11.9%, P = 0.001) and more likely to be associated with QT(c) ≥440 ms (difference = 11.0%, 95% CI 2.6, 19.0%, P = 0.013). The QT nomogram was associated with a lower false positive rate than widely accepted QT(c) criteria, and allowed detection of different effects of individual drugs. The nomogram offers potential advantages over QT(c) criteria and merits further investigation in a clinical setting.

Metabolic acidosis and generalized seizures secondary to citalopram overdose: a case report

Selective serotonin re-uptake inhibitors (SSRIs) are widely used in the community for treating many forms of mental illnesses. Citalopram, a newer generation SSRI, is commonly prescribed, but despite its low toxicity profile has a potential to cause seizures and dysarrythmias in overdose. Data on citalopram overdose-induced metabolic acidosis are scarce. There have been only three cases of metabolic acidosis reported in the literature due to citalopram overdose in humans and we are reporting the fourth one. We report a case of citalopram overdose with metabolic acidosis and generalized seizure. To our best knowledge, this is the first case reported in Saudi Arabia.

High dose insulin in toxic cardiogenic shock

Objective. To report the successful use of high dose insulin (HDI) in previously unreported insulin dosing ranges in a patient with severe myocardial toxicity due to an amitriptyline and citalopram overdose. Case Report. A 65-year-old female presented in respiratory arrest, which was followed by bradycardic pulseless electrical activity after ingesting multiple medications. After a prolonged resuscitation, the patient was maintained only on infusions of norepinephrine (40 mcg/min), vasopressin (4 units/h), insulin (80 units/h), and sodium bicarbonate. Due to a deteriorating clinical condition and limited prognosis, the insulin infusion was titrated incrementally upwards to 600 units/h (6 units/kg/h) over a 5 h time period while simultaneously completely weaning off both vasopressors. She developed brisk pulses and warm extremities, and her cardiac output nearly tripled. After 2 days of stabilization the insulin was slowly tapered, and the patient recovered. Discussion. HDI as a single cardiovascular agent significantly improved clinical and cardiovascular parameters after the failure of vasopressor therapy in severe cardiovascular toxicity. Higher doses of insulin than previously recommended may be needed in toxic poisonings when severe myocardial depression is present.

Comparison of Toxicity of Acute Overdoses with Citalopram and Escitalopram

Seizures and QTc prolongation are associated with citalopram poisoning; however, overdose experience with escitalopram is more limited. The goals of this study were to compare citalopram's vs. escitalopram's clinical effects in overdose, including the incidence of seizures. A retrospective review was conducted for single-substance acute overdoses with citalopram and escitalopram, managed in hospitals, that were reported to six U.S. poison centers from 2002-2005. There were 374 citalopram and 421 escitalopram overdose cases. Gender and ages were similar between the two, with 68-70% females and a median age of 20 years for citalopram and 18 years for escitalopram. Median dose by history was 310 mg for citalopram and 130 mg for escitalopram. More serious outcomes were associated with citalopram overdoses (p < 0.001). Most frequently reported clinical effects with citalopram and escitalopram were tachycardia, drowsiness, hypertension, and vomiting. Seizures (30 vs. 1, respectively, p < 0.001) and tremor (32 vs. 13, respectively, p = 0.001) were more common with citalopram. QTc prolongation occurred in 14 citalopram cases and 7 escitalopram cases (p = 0.109). There was an association between increasing dose and severity of outcome for citalopram (p < 0.001) and escitalopram (p = 0.011). In children < 6 years old, 12 of 66 citalopram and 5 of 57 escitalopram cases experienced toxicity, such as drowsiness, nausea/vomiting, and tachycardia. There were no seizures in this age group. Escitalopram seems to be less toxic than citalopram after an acute overdose; seizures and tremors were more common with citalopram. Initial management of overdoses should include seizure precautions for citalopram and cardiac monitoring for both drugs.

Predictive factors for generalized seizures after deliberate citalopram overdose

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. 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. 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. 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.

Severe hypoglycaemia in citalopram overdose

We present two episodes of poisoning with citalopram in which the main feature was profound hypoglycaemia. Citalopram has been regarded as the most toxic of the selective serotonin reuptake inhibitors in overdose; however, hypoglycaemia is not one of the documented features of overdose. This is an important component of the toxicological profile of citalopram and a treatable cause of seizure activity that should be reported in poisoning information references.