Antidepressant Overdose Research Articles

Prolonged Use of Intravenous Lipid Emulsion in a Severe Tricyclic Antidepressant Overdose

Intravenous lipid emulsion (ILE) resuscitation is now frequently being used for severe overdoses due to lipophilic drugs. However, the optimal dose, duration, and safety are still unclear. A patient with refractory cardiovascular collapse following an amitriptyline overdose was treated with ILE with initial improvement. Instability recurred after ILE discontinuation and lipid therapy was restarted, but high-dose treatment was complicated by severe lipemia. A low-dose infusion was instead used, and the patient did not experience further toxicity despite amitriptyline levels in the toxic range for 21days. He survived to discharge without long-term sequelae. A low-dose infusion of ILE was well tolerated and may have successfully prevented recurrent toxicity in a case of severe tricyclic antidepressant overdose.

Comparison of Intravenous Lipid Emulsion, Bicarbonate, and Tailored Liposomes in Rabbit Clomipramine Toxicity

Liposome (LIP)-like lipid dispersions have emerged as useful detoxification vehicles in vitro. The authors compare resuscitation with tailored LIPs, 20% intravenous lipid emulsion (ILE), and sodium bicarbonate (BIC), in a rabbit model of clomipramine toxicity. Sedated, instrumented New Zealand white rabbits underwent clomipramine infusion at 3.2mg/kg/min to 50% baseline mean arterial pressure (MAP) and then at 1.6mg/kg/min for 30minutes. BIC (3mL/kg 8.4%), ILE (3mL/kg 20%), or LIP (24mg/kg) were infused as rescue treatments at toxicity and were repeated at 10minutes (n=5 in each group). Thirty-minute MAP was greatest in ILE-treated animals: 61mmHg ILE (interquartile range [IQR]= 49 to 64mmHg), 43mmHg LIP (IQR= 36.5 to 49mmHg), and 10mmHg BIC (IQR= 10 to 44mmHg; all p=0.02). Two of the five BIC-treated animals survived to 30minutes, compared with all five of the ILE-treated animals and all five of the LIP-treated animals (p=0.044). Both ILE and LIPs improved hemodynamic recovery compared with bicarbonate in clomipramine-induced cardiotoxicity in rabbits. Greater 30-minute MAP was observed in the ILE group.

Intravenous lipid emulsion therapy – The fat of the land

Summary Local anaesthetic agents are utilised ubiquitously in clinical practice, and as such potentially grave adverse events such as systemic toxicity can occur. Although the use of ultrasound, and nerve stimulator guided administration have reduced the risk of such adversities, they unfortunately have not been eliminated. This review examines the pharmacology and toxicology of local anaesthetic agents and the use of Intravenous Lipid Emulsion (ILE) to counteract the systemic toxic effects. The research underpinning the ‘Lipid Sink' and ‘Lipid Flux' theories of ILE mechanism of action are explored, as is the novel and successful use of ILE in other lipophilic drug toxidromes, such as overdoses of tri-cyclic antidepressants and calcium channel antagonists. Also discussed are the potential direct and indirect risks associated with the use of intravenous lipid treatments and the possibility for reporting bias in the literature. Despite this, case reports of the successful use of ILE are certainly compelling, and have led to the rapid adoption of ILE in clinical practice and the recommendation for its use by anaesthetic associations worldwide.

Recreational amitriptyline toxicity mimicking basilar artery stroke

Departments of aAgeing & Health bAccident & Emergency Medicine, St Thomas’ Hospital, London, UK Correspondence to Jonathan Birns, BSc, MBBS, MRCP, PhD, Department of Ageing & Health, 9th Floor, North Wing, St Thomas’ Hospital, London SE1 7EH, UK Tel: +44 207 188 2515; fax: +44 207 928 2339; e-mail: [email protected] Received February 10, 2012 Accepted March 29, 2012

Heart rate variability in children with tricyclic antidepressant intoxication

Tricyclic antidepressant (TCA) intoxication is among the most common causes of poisonings in our country. The TCA group of drugs affects the central nervous and cardiovascular systems, resulting in severe arrhythmia and death. Heart rate variability (HRV) analysis is a non-invasive assessment method that allows evaluation of the cardiac autonomic (sympathetic and parasympathetic) activity. The aim of this study was to evaluate HRV in children requiring ICU stay due to TCA poisoning.

Suspected Tricyclic Antidepressant Overdose Successfully Treated With Lipids

Suspected Tricyclic Antidepressant Overdose Successfully Treated With Lipids

A review of the suitability of duloxetine and venlafaxine for use in patients with depression in primary care with a focus on cardiovascular safety, suicide and mortality due to antidepressant overdose

Depression and anxiety disorders are among the most common disorders treated by general practitioners (GPs) in the UK. Since both disorders are associated with a significantly increased risk of suicide, including with antidepressant overdose, the safety of antidepressants in overdose is of paramount importance. Numerous updates relating to antidepressant safety have been issued by regulators in the UK which may have eroded GP confidence in antidepressants. Venlafaxine, a serotonin nor adrenaline reuptake inhibitor (SNRI) had primary care prescribing restrictions placed on it in 2004 due to concerns about cardiotoxicity and mortality in overdose. Although a review of the evidence led to a reversal of the majority of restrictions in 2006, evidence suggests GPs may still be cautious in their prescribing of venlafaxine and possibly other SNRI antidepressants for patients with depression and anxiety disorders. This paper reviews the evidence pertaining to the safety of SNRI antidepressants from a perspective of cardiovascular safety and overdose. The currently available evidence suggests a marginally higher toxicity of venlafaxine in overdose compared with another SNRI duloxetine and the selective serotonin reuptake inhibitors (SSRIs), although this may be related to differential patterns of prescribing in high-risk patients. Based on this review SNRIs have a positive risk benefit profile in the treatment of depression and generalized anxiety disorder in primary care, especially as second-line agents to SSRIs.

ST-T segment changes in patients with tricyclic antidepressant poisoning.

Objective:Tricyclic antidepressant (TCA) poisoning is among highly prevalent and potentially dangerous toxicities. ST-T changes are observed in the electrocardiogram (ECG) of most of TCA poisoned patients. We aimed to study ST-T segment changes in TCA toxicity and its probable relationship with other ECG findings.Methods:This retrospective study was carried out in Noor and Ali Asghar University Hospital, Isfahan (Iran) in 2012. Patients with TCA toxicity based on the patients’ history who had not consumed any cardio-active drugs and did not have a past medical history of cardiovascular disease in the recent 5 years, were randomly selected and investigated. Their demographic and medical data on admission including ECG, age, sex, type and amount of ingested TCA, poisoning severity score, QRS changes, QT interval, heart axis position and R-wave were all recorded. ST-T changes and their relation with other ECG parameters have been determined using statistical analysis.Findings:Medical records of 272 patients were analyzed. In symptomatic patients, ST change prevalence was 40.8% and T change prevalence was 9.5%. In asymptomatic patients, the frequency of ST and T changes were 4.8% and 0.8%, respectively (P < 0.05). The most common ST and T changes in baseline (on admission) ECG were non-significant elevation (15.4%), significant elevation (11%) in pre-cordial leads, and T-wave flattening (6.6%). A statistically significant correlation was documented between ST segment changes with QRS and R-wave in aVR. The correlation between T-wave changes and R-wave in aVR lead was also significant.Conclusion:ST-T changes in TCA poisoned patients are more prevalent in symptomatic patients. Obviously for a more definite conclusion, it is necessary to design a prospective study with the control group. This may facilitate a better understanding of ST-T segment changes.

Crack Cocaine-Induced Cardiac Conduction Abnormalities Are Reversed by Sodium Bicarbonate Infusion

We report a dramatic case of a 19-year-old man with crack cocaine overdose with important clinical complications as cardiac arrest due to ventricular fibrillation and epileptics status. During this intoxication, electrocardiographic abnormalities similar to those found in tricyclic antidepressant poisoning were observed, and they were reversed by intravenous sodium bicarbonate infusion.

Heart Rate Variability in Children with Tricyclic Antidepressant Intoxication

The aim of this study was to evaluate HRV in children requiring intensive care unit stays due to TCA poisoning between March 2009 and July 2010. In the time-domain nonspectral evaluation, the SDNN (P < 0.001), SDNNi (P < 0.05), RMSDD (P < 0.01), and pNN50 (P < 0.01) were found to be significantly lower in the TCA intoxication group. The spectral analysis of the data recorded during the first 5 minutes after intensive care unit admission showed that the values of the nLF (P < 0.05) and the LF/HF ratio (P = 0.001) were significantly higher in the TCA intoxication group, while the nHF (P = 0.001) values were significantly lower. The frequency-domain spectral analysis of the data recorded during the last 5 minutes showed a lower nHF (P = 0.001) in the TCA intoxication group than in the controls, and the LF/HF ratio was significantly higher (P < 0.05) in the intoxication group. The LF/HF ratio was higher in the seven children with seizures (P < 0.001). These findings provided us with a starting point for the value of HRV analysis in determining the risk of arrhythmia and convulsion in TCA poisoning patients. HRV can be used as a noninvasive testing method in determining the treatment and prognosis of TCA poisoning patients.

Morbidity and Mortality Predictors in Patients with Acute Tricyclic Antidepressant Toxicity

Tricyclic antidepressant (TCA) drugs are well known medications for depression, nocturnal enuresis and chronic pain. The severe morbidity and mortality associated with these drugs is well documented due to their cardiovascular and neurological toxicity. The aim of this study is to predict the morbidity and mortality factors in patients with acute TCA toxicity in relation to outcome toxicity measures (coma grade, ECG findings and duration of hospitalization) and to detect early evidence of cardiotoxicity using quantitative analysis of Troponin I. The present study was conducted on 100 patients presented to the PCC of Ain Shams University hospitals during the period from October 2009 to March 2011 with acute TCA toxicity of both sex and different ages. Patients were divided into 3 groups according to poisoning severity score (PSS) into group I (mild toxicity), group II (moderate toxicity) and group III (severe toxicity). All subjects were examined for:I) sociodemographic data;II) medical evaluation; III) investigations including arterial blood gases, serum electrolytes (Na and K), random blood sugar, serum troponin I level and electrocardiography (ECG) monitoring; IV) outcome including coma grade, ECG findings and duration of hospitalization. Risk factors (sex, coingestion, time delay and previous attempts) had no effect on difference between groups, while age and mode of toxicity were significantly different (p-value 100 msec, cardiac dysrhythmias, altered mental status, seizures, respiratory depression and hypotension) had a high significant effect (p-value 0.05) with all risk factors except for the age and the mode of poisoning. Duration of hospitalization (DOH) had a highly significant (p-value 0.05) with all risk factors except for the dose of TCA. Level of troponin I was non evident in predicting cardiotoxicity. Conclusion: Reed's coma scale is an indicator either for evaluation of poisoning severity in individual TCAs or for assessment of relative toxicity between different types of TCAs. ECG findings especially QRS duration is an easy, cheap and available diagnostic tool in Emergency Room (ER) to help not only in diagnosing TCA poisoning but also in predicting its severity and occurrence of other complications.

Comparison of lipid sinks in sequestering common intoxicating drugs

Intravenous lipid emulsion is a recommended treatment for local anesthetic intoxication. The lipid sink theory hypothesizes that the mechanism behind the lipid treatment is the entrapment of toxic drugs in plasma, preventing them from reaching target receptors. Lipid sink treatment has also been used as a last refuge treatment for severe tricyclic antidepressant intoxication with seemingly beneficial results. We selected three drugs, i.e. amiodarone, ketamine, and amitriptyline, that can cause severe intoxication and compared their interactions with two commercial fat emulsions (Intralipid® and ClinOleic®) and one synthetic liposome (80:20 mol% phosphatidylcholine/phosphatidylglycerol) dispersion. The interaction studies were carried out by capillary electrokinetic chromatography and the retention factors and distributions constants of the drugs were calculated. The results demonstrate that there is stronger interaction between the drugs and the synthetic liposome dispersion than with the commercial emulsions.

Clinical use of antidepressant therapy and associated cardiovascular risk.

A number of different psychotropic agents have been associated with an increased risk of cardiovascular disease, and these relationships have been difficult to interpret due to the presence of confounding factors. Recently, there has been renewed interest in the potential for certain antidepressants to cause QT prolongation, which is a predisposing factor for arrhythmia. However, the optimum means of determining QT remains contentious due to discrepancies between methods that may be readily applied in a clinical setting versus more detailed techniques during regulatory assessment. A number of different pharmacological mechanisms might explain the occurrence of adverse cardiac effects, and these differ according to the type of antidepressant agent. Emerging data indicate that citalopram exhibits a dose-effect relationship for QT prolongation. Whereas cardiotoxicity is readily apparent in the context of intentional antidepressant overdose, the occurrence of cardiac effects as a result of therapeutic administration is less certain. Pre-existing cardiac disease and other factors that independently predispose to arrhythmia are important considerations. Therefore, clinical judgment is needed to evaluate the overall risk or benefit of a particular antidepressant in any patient. Close monitoring should be considered for those at greatest risk of QT prolongation and arrhythmia.

Chewing the fat: A case report on intravenous lipid emulsion to reverse cardiotoxicity from intentional amitriptyline overdose.

Abstract Introduction Tricyclic antidepressant overdoses are a common presenting problem to emergency centres in South Africa. Case history A 20-year-old female was brought to the emergency centre in status epilepticus due to tricyclic antidepressant toxicity. Discussion Toxicity was manifested as severe haemodynamic instability that did not respond to standard therapy, and was subsequently treated with intravenous fat emulsion (ILE) therapy. The patient recovered with a survival to hospital discharge, neurologically intact.

A Case of Drug Overdose–Induced, Severe Electrocardiogram Abnormalities

To the Editor: We report a case of a patient with concomitant overdose of antidepressants and antianxiety agents, and we also discuss the need for measurement of drug concentrations in plasma.

Response to “Tricyclic antidepressants intoxication in Tehran, Iran: epidemiology and associated factors”

I read with interest the study entitled ‘‘Tricyclic antidepressants intoxication in Tehran, Iran: epidemiology and associated factors.’’ I commend the authors for their study on identifying the individuals prone to tricyclic antidepressant (TCA) intoxication. Since it seems that their method for control selection is not correct, I have a few questions regarding their methodology as well as how to interpret the results. They have mentioned that they have divided the patients into two groups of TCA intoxication (case group) and the patients who had been poisoned by some other drug classes (control group). Can they provide more details regarding the type of the other drug classes in ‘Non-TCA intoxicated group?’ They have not presented the frequency of intoxication with each type of drug in this group, while they have even mentioned the number of the patients intoxicated by different types of TCAs in their ‘Results.’ Is it not necessary to present such a data in such type of study? Did they compare the level of consciousness of the patients intoxicated with the medications that do not usually decrease the level of the consciousness, for instance, those intoxicated by calcium channel blockers, digoxin, antimicrobials, or anticoagulants to the ones with TCA intoxication? If they did, is such a comparison correct? Another concern I had about the study is that the authors have compared a combination of the accidental and intentional intoxications in the two groups of the study. In this case, what is the value of the comparison of for example the marital status or the status of employment between the patients in the two study groups (as illustrated in Table 2)? Did not they have to compare the patients’ characteristics between the separated accidental and intentional poisoning groups? It seems that if we would like to identify the determinants of the TCA intoxication, we should compare the TCA-poisoned patients with a homogenously drug-poisoned group of the patients (for example, the intoxications induced by other types of antidepressants such as serotonin reuptake inhibitors, monoamine oxidase inhibitors, or antipsychotics, etc.). Did the authors perform such a comparison? It seems then that their results and conclusion is not correct due to their biased control selection.

Tricyclic antidepressant overdose necessitating ICU admission

Tricyclic antidepressant (TCA) overdose necessitating intensive care unit (ICU) admission remains a significant problem in the Western Cape. In this retrospective study, we reviewed the course of life-threatening TCA overdose in our centre to identify potential prognostic indicators. TCA levels >1000 ng/ml were associated with QT and QRS prolongation and convulsions. However, no single parameter predicted non-survival. The overall mortality of TCA overdose was very low. Our findings should encourage clinicians to offer medical care including ICU admission, if necessary, to patients with TCA overdose.

Lipid therapy for the treatment of a refractory amitriptyline overdose

Tricyclic antidepressant (TCA) overdose is a leading cause of death among intentional overdoses. Intravenous lipid emulsion therapy is an emerging antidote for local anesthetic toxicity, and there is animal evidence that lipid therapy may be efficacious in TCA overdose. Furthermore, case reports in humans have described the use of lipid therapy to reverse the toxicity of other lipophilic drugs. Here we report a 25-year-old female presenting with coma and hemodynamic instability following intentional ingestion of amitriptyline. She had multiple episodes of pulseless wide-complex tachycardia despite conventional treatment with chest compressions, cardioversion, lidocaine, epinephrine, norepinephrine, magnesium sulphate, sodium bicarbonate, activated charcoal, and whole bowel irrigation. Twenty percent lipid emulsion was administered intravenously (an initial 150 mL bolus, followed by an infusion at 16 mL/h and a second bolus of 40 mL) over 39 hours (total dose 814 mL) yet resulted in no dramatic changes in hemodynamics or level of consciousness. However, there was a decrease in the frequency of wide-complex tachycardia during the lipid emulsion infusion and a recurrence of wide-complex tachycardia shortly after the infusion was stopped. The patient was discharged from the intensive care unit 11 days later with no lasting physiologic sequelae.

Severe overdose of quetiapine treated successfully with extracorporeal life support

Background. Quetiapine is a second-generation antipsychotic drug, used mainly in the treatment of psychotic disorders. Overdose is associated with sedation, tachycardia and a prolonged QT-interval on the ECG. Cardiovascular symptoms are uncommon but in severe cases profound cardiovascular depression may occur. Objectives. To report a case where extracorporeal circulatory support (ECCS) was used successfully in severe quetiapine overdose. Case report. A 40-year-old woman was admitted to the emergency department (ED) with reduced consciousness apparently due to intoxication. She had a history of schizophrenia and was treated with 900 mg of quetiapine daily. In the ED, she presented with immeasurable low blood pressure, irregular bradycardia, hypothermia and a Glasgow Coma Scale (GCS) of 8. An immunoassay test for tricyclic antidepressive agents (TCA) was positive. Despite resuscitation with intravenous fluids, intensive vasopressor treatment and renal replacement therapy (CRRT) the patient's condition deteriorated. The patient was quickly moved to an intensive care unit where ECCS could be instituted. The patient subsequently recovered after 4 days in the ICU without any residual symptoms. Further laboratory analysis did not confirm the immunoassay finding. Conclusions. Severe poisoning with quetiapine may imitate tricyclic antidepressant poisoning, and drug screening methods may be falsely positive for TCA. In case of cardiovascular collapse due to quetiapine overdose, ECCS may be life saving.

Tricyclic antidepressant poisoning treated by magnesium sulfate: a randomized, clinical trial

Tricyclic antidepressant (TCA) poisoning is a major problem in medicine, with a high morbidity and mortality rate. The main cause of fatality is cardiac arrhythmias resulting from intoxication. Sodium bicarbonate is the drug of choice, but severe poisoning necessitates further interventions. Magnesium sulfate seems to be effective in this condition. In a randomized, clinical trial, we evaluated all patients with a history of TCA intoxication referred to the Loghman Hakim Hospital Poison Center. The patients were randomly divided into two groups: one treated by bicarbonate infusion (control group) and the other (case group) by the infusion of magnesium sulfate in addition to the treatment in the first group. Seventy-two patients were recruited into the study (36 cases and 36 controls). Mean duration of intensive care unit stay in the cases and controls were 25.63 ± 9.33 and 82.67 ± 21.66 hours, respectively (P < 0.001). Mortality rate in the case group was 13.9% and 33.3% in the other group (P = 0.052). Magnesium sulfate can be an effective drug in the treatment of TCA poisoning; however, several randomized, clinical trials are still necessary to confirm this.