Antidepressant Intoxication Research Articles

A case of diphenhydramine intoxication showing prolonged false positive tricyclic antidepressant in the urine assay.

The urine immunochromatographic assay is a useful screening tool for patients suspected of acute drug intoxication in emergency conditions. Diphenhydramine intoxication shows symptoms similar to those of tricyclic antidepressant (TCA) intoxication. We examined a case of diphenhydramine intoxication showing cerebellar ataxia and prolonged false positive results for TCA in the urine. The urine TCA test showed persistently positive results even 60 h after the patient's initial drug screening. We observed negative conversion 90 h after the initial drug screening. Considering the similarities of clinical symptoms between diphenhydramine and TCA intoxication, emergency physicians should consider the possibility of cross-reactivity in the diagnosis of a patient with unknown acute drug intoxication showing positive results of TCA immunochromatographic assay in the urine. The present case suggests that diphenhydramine overdose may cause cerebellar ataxia and show prolonged cross-reactivity as TCA in the urine.

Prolonged coma due to amitriptyline overdose and genetic polymorphism: a case report

BackgroundReduced consciousness has a wide variety of possible causes, not infrequently being toxic in nature. An intoxication might be obvious, but in this paper an unexpected case with a tricyclic antidepressant is presented.Case presentationA 76-year-old caucasian female was found unconscious. Primary diagnostic evaluation, including a negative drugs of abuse test, did not give direction to any clear cause. Yet an intraventricular conductive disorder with widening of the QRS complex and electroencephalogram abnormalities did suggest a possible drug effect. Heteroanamnestic information led to the suspicion of an amitriptyline intoxication, which was confirmed by further laboratory analysis. The patient remained comatose for several days. High concentrations of amitriptyline indicated a large overdose of amitriptyline and, in combination with a cytochrome P450 2D6 poor metabolizer status, could explain the long persistence of her comatose state.ConclusionWe present a tricyclic antidepressant intoxication, where the patient is thought to have taken a large amount of amitriptyline at once, which, in combination with a cytochrome P450 2D6 poor metabolizer status, led to an unusual long persistence of her coma.

Amitriptyline Intoxication in Children: Twenty Years' Experience in a Tertiary Care Center in Turkey.

Amitriptyline ingestion is an important cause of poisoning morbidity and mortality in Turkey and other countries. In contrast to adults, data concerning amitriptyline intoxication in children are limited. The purpose of this study was to investigate amitriptyline intoxication findings in the pediatric population, based on age groups and reported dosages. The medical records of 192 patients admitted to the Karadeniz Technical University Medical Faculty Farabi Hospital Pediatric Emergency Department, Turkey, due to amitriptyline intoxication in 1997-2017 were examined retrospectively. Patients were divided into 6 groups based on amitriptyline doses and 4 groups based on age. Complete blood count, blood glucose, serum electrolytes, renal and liver function tests, coagulation tests (prothrombin time and partial thromboplastin time), and blood gas analysis were studied in all patients. Electrocardiography was performed on all children, and chest radiography and electroencephalography on those with respiratory or central nervous system symptoms. Amitriptyline intoxication was most frequently observed between the ages of 1 and 4 years. The most common signs and symptoms observed at time of hospital admission were lethargy and drowsiness (45.3%), sinus tachycardia (19.2%), and nausea and vomiting (13%). The most common laboratory finding was hyperglycemia (17.7). Six patients were intubated because of respiratory failure, and mechanical ventilation was initiated in these cases. One patient with amitriptyline overdose had persistent supraventricular tachycardia. Four children died due to amitriptyline intoxication. Tricyclic antidepressant intoxication is a leading cause of mortality and morbidity in children. It is therefore particularly important to identify the clinical and laboratory findings that develop with high-dose consumption.

'Stadium wave-like' ventricular contraction due to extreme conduction delay in tricyclic antidepressant intoxication.

'Stadium wave-like' ventricular contraction due to extreme conduction delay in tricyclic antidepressant intoxication.

Endoscopic removal of a gastric pharmacobezoar induced by clomipramine, lorazepam, and domperidone overdose: a case report

IntroductionGastric pharmacobezoars are a rare entity that can induce mechanical gastric outlet obstructions and sometimes prolong toxic pharmacological effects. Certain medications, such as sustained-release forms, contain cellulose derivatives that may contribute to the adhesion between pills and lead to the creation of an aggregate resulting in a pharmacobezoar. Case reports are rare, and official guidelines are needed to help medical teams choose proper treatment options.Case presentationOur patient was a 40-year-old Caucasian woman with borderline personality disorder and active suicidal thoughts who was found unconscious after a massive drug consumption of slow-release clomipramine, lorazepam, and domperidone. On her arrival in the emergency room, endotracheal intubation was preformed to protect her airway, and a chest x-ray revealed multiple coffee grain-sized opaque masses in the stomach. She was treated with activated charcoal followed by two endoscopic gastric decontaminations 12 h apart in order to extract a massive gastric pharmacobezoar by manual removal of the tablets.ConclusionThis case demonstrates that in the case of a massive drug consumption, a pharmacobezoar should be suspected, particularly when cellulose-coated pills are ingested. Severe poisoning due to delayed drug release from the gastric aggregate is a potential complication. Detection by x-ray is crucial, and treatment is centered on removal of the aggregate. The technique of decontamination varies among experts, and no formal recommendations exist to date. It seems reasonable that endoscopic evaluation should be performed in order to determine the appropriate technique of decontamination. Care should be patient-oriented and take into account the clinical presentation and any organ failure, and it should not be determined solely by the suspected medication ingested. Thus, serum levels are not sufficient to guide management of tricyclic antidepressant intoxication.

Tricyclic Antidepressant Drug Intoxication: Is there a Role for Lipid Emulsion Therapy?

Lipid resuscitation therapy is the administration of Intravenous Lipid Emulsions (ILE) with the intent of reducing the clinical manifestations of toxicity from drug overdoses; including local anesthetics, calcium-channel blockers, β- blockers, antipsychotics, tricyclic antidepressant drugs (TCAD) and other compounds. Although there are conflicting findings in the literature, ILE may be considered for resuscitation in emergency and intensive care in resuscitation of severe hemodynamic compromise by TCAD. This article reviews recent literature to analyse consequences, and intended effects associated with this treatment modality in poisoning with TCAD.

Tricyclic Antidepressant Intoxication; Several Complications after an Acute Poisoning by Amitriptyline and Clomipramine

Tricyclic antidepressant (TCA) toxicity is common among children and adults due to widespread use. Tricyclic ant depressive drugs are widely used in suicide attempts and present a variety of deleterious effects. In this case report we present a patient with severe poisoning by ingestion of amitriptyline and clomipramine in which many complications were observed.

Varicella zoster virus (VZV) in cerebral arteries of subjects at high risk for VZV reactivation

With a decline in varicella zoster virus (VZV)-specific cell-mediated immunity, VZV can reactivate, infect cerebral arteries and cause stroke. Previous studies of cerebral arteries from subjects without a history of transient ischemic attacks or stroke revealed no VZV DNA or VZV antigen; however, VZV DNA and VZV antigen were found in the cerebral arteries of a subject with diabetes, a known risk factor for VZV reactivation and zoster. The present study analyzed an additional 55 cerebral arteries from 18 subjects with co-morbidities that may increase risk of VZV reactivation: a history of alcohol abuse, tricyclic antidepressant intoxication, cocaine abuse, HIV or being over age 70years. VZV antigen was detected in 24 (44%) cerebral arteries from 14 (78%) subjects.

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.

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.

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.

Case report: successful lipid resuscitation in multi-drug overdose with predominant tricyclic antidepressant toxidrome

We report a case of profound neurologic and cardiovascular manifestations of tricyclic antidepressant intoxication following self-poisoning with multiple pharmaceuticals including amitriptyline in excess of 43 mg/kg, in a 51-year-old male. Institution of mechanical ventilation, volume expansion, systemic alkalinisation (pH 7.51), and intermittent bolus metaraminol resulted in QRS narrowing but failed to resolve the developed shock. One 100-ml bolus of 20% lipid emulsion followed by a further 400 ml over 30 min was administered with restoration of haemodynamic stability, thereby curtailing the need for ongoing vasopressor medications. Assayed blood levels were consistent with the 'lipid sink' being a major effecter in the observed improvement.

Suicide attempts with amitriptyline in adults: a prospective, demographic, clinical study

There are several studies on tricyclic antidepressant (TCA) intoxication in the literature; however, there is no specific study on amitriptyline, a specific TCA, intoxication. Materials and methods: Forty adult patients who had been admitted to the emergency department due to suicide attempts with amitriptyline were included. Medical and social histories of the patients were obtained. The estimated amount of amitriptyline ingested was determined. The psychiatric support and psychiatric diagnosis were all recorded. All patients were contacted by phone 6 months later. Results: Main reason of suicidal attempt was family problems. The stated amount of ingested amitriptyline by the patient or parents was between 60 mg and 1250 mg. Mean cost of diagnosis and treatment were US$ 87.9 ± 83.5 and US$ 290.5 ± 164.8, respectively. Somnolence was the main complaint. Sinus tachycardia and hypocalcaemia were the most common findings. Seven and a half percent of the patients had a GCS score under 8. There was a significant negative correlation between mean arterial pressure and the estimated ingested amitriptyline dose. After discharge, 52.5% of the patients visited the psychiatry outpatient clinics. There was only 1 patient with recurrent suicidal attempt. Conclusion: Amitriptyline was usually abused by young females in our region. Drowsiness, dizziness, and urinary retention were the most common clinical features. Family conflicts and communication problems were the most cited reasons of suicide attempts.

Alterações eletrocardiográficas na intoxicação aguda por antidepressivo tricíclico e suas implicações clínicas

Introdução: A intoxicação aguda por antidepressivos tricíclicos é comum nas salas de emergência. Anormalidades no eletrocardiograma de 12 derivações (ECG) são associadas a este tipo de intoxicação, com implicações diagnósticas e prognósticas. O ECG pode ter valor incremental principalmente em situações de alteração de consciência, convulsões ou distúrbios do ritmo cardíaco associado. Objetivo: Revisar as principais alterações eletrocardiográficas descritas na intoxicação por antidepressivos tricíclicos e estabelecer suas implicações prognósticas no manejo desta condição clínica. Metodologia: Pesquisa bibliográfica no MEDLINE (PubMEd) limitada aos artigos publicados entre 1980 e 2010 em língua inglesa, utilizando-se unitermos (tricyclic antidepressant overdose OR tricyclic antidepressant intoxication OR tricyclic antidepressant poisoning OR tricyclic antidepressant ingestion AND electrocardiography). Dos 133 artigos identificados, foram selecionados 44 para a revisão. Resultado: Foram identificados como alterações prevalentes com poder diagnóstico em ordem decrescente os seguintes achados: desvio dos 40 ms terminais do QRS para a direita do plano frontal (61,0-83,0%), taquicardia sinusal (40,7-57,7%), prolongamento do QTc (8,2-53,0%),relação R/S em aVR>0,7 (28,8-32,9%), prolongamento do QRS (8,2-21,3%) e padrão Brugada-like (2,3-15,3%). Destes achados, somente o prolongamento do QRS foi prognóstico para morte, convulsão e arritmia e o prolongamento do QTc e a relação R/S em aVR>0,7 para arritmia ventricular. Para o padrão Brugada-like , as evidências são escassas, mas sugestivas de maior chance de convulsão e hipotensão. Conclusão: O ECG é um instrumento de fácil realização na sala de urgência, fornecendo informações diagnósticas e prognosticas para a intoxicação por tricíclicos, devendo ser realizado em todo paciente com suspeita desta intoxicação.

Tricyclic antidepressants intoxication in Tehran, Iran: Epidemiology and associated factors

Tricyclic antidepressant (TCA) intoxication contributes a large number of drug toxicities with serious complications. There are a few studies about factors associated with TCA intoxication. This study therefore aimed to identify determinants of this type of intoxication. A cross-sectional study was carried out at Loghman-Hakim Poison Hospital during a 6-month period. All poisoned patients aged >12 years presented to this hospital during the mentioned period were evaluated. Then, TCA-poisoned patients were compared with other drug intoxications as the control group to determine factors associated with TCA intoxications. There were 9809 admissions, of which 1583 (16.1%) patients including 601 (38%) males were intoxicated with TCAs. Mean age of the subjects was 26.5 + 10 years. Most of the TCA intoxications (74.4%) were intentional (p = 0.01). Amitriptyline was the most frequent agent followed by Nortriptyline. There was no significant difference between TCA and non-TCA intoxications regarding the mortality (1.3% in TCA vs. 1.1% in others, p = 0.45). Logistic regression analysis revealed that sex, addiction status, and history of psychological problems have association with TCA intoxication. The results of this study are helpful in identifying individuals who are prone to TCA intoxication and may be useful in implementation of preventive strategies.

Terlipressin as an adjunct vasopressor in refractory hypotension after tricyclic antidepressant intoxication

To report the management of cardiovascular failure refractory to standard catecholamine therapy with terlipressin in a patient with tricyclic antidepressant (TCA) intoxication. A 41-year-old woman, with suicidal ingestion of 11.25 g amitriptyline and 1500 mg diclofenac, was admitted to the emergency department. After 30 min in ventricular fibrillation, with ongoing CPR, she regained a potentially perfusing rhythm, but with hypotension refractory to standard catecholamine therapy with adrenaline, 2 microg/kg/min (norepinephrine); adrenaline, 1 microg/kg/min (epinephrine) until 55 min after admission. An injection of 1 mg terlipressin restored mean arterial blood pressure >65 mmHg within 10 min. Ten hours after admission to the intensive care unit, catecholamine support could be withdrawn because of a stable haemodynamic state. Within 7 days, all organ function recovered, and the patient regained full neurological function. Successful management of cardiovascular failure with terlipressin after TCA intoxication refractory to catecholamines suggests a potential role for terlipressin as an adjunct vasopressor in severely hypotensive patients.

Seizures associated with poisoning in children: tricyclic antidepressant intoxication

The aim of this study was to examine the characteristics of seizure due to poisoning. This was a retrospective analysis, throughout 4 years of hospital admissions for poisoning. Data of patients with seizures due to poisoning were evaluated with respect to the causes, frequencies and complications of seizures. Among the 1561 admissions due to intoxication during the review period, seizures developed in 26 cases (1.6%). Tricyclic antidepressant overdose (n = 11, 42%) was the leading cause of seizure due to poisoning. Generalized tonic-clonic seizures were observed in 24 patients. Status epilepticus developed in six patients (23%). Mechanical ventilation was applied in 12 (46%) patients. Cardiac complications were observed in 11 (42%) patients with seizures. Two patients who had cardiac arrest due to acepromazine maleate and imipramine intoxication died. One of the causes of seizures in pediatric age group is intoxication. Seizures due to intoxications may cause serious clinical conditions. Intoxications should be thought when a patient is admitted with the diagnosis of afebrile seizure even if there is no history of drug intake.

Brugada‐like ECG abnormalities during thioridazine overdose

A previously healthy 58-year-old woman was comatose when admitted to our emergency department. Physical evaluation showed muscular rigidity, opisthotonus, external-rotation of upper limbs in response to painful stimulation and neck stiffness. Arterial blood pressure (120/80 mmHg) and temperature (36.5 °C) were unremarkable. The ECG showed sinus rhythm with significant QT lengthening (Figure 1A). A CT scan of the brain and evaluation of spinal fluid were normal. The patient was intubated and mechanically ventilated. Figure 1 (A) Sinus rhythm with significant QT lengthening; (B) Brugada-like pattern; (C) Normal ECG A few hours after admission, we learnt that the patient's husband was being treated with haloperidol and risperidone. The ECG recorded the day after evolved into a Brugada-like pattern (Figure 1B). Over the next 72 h, both the ECG and the clinical abnormalities resolved (Figure 1C), and she was extubated on day 3. She denied deliberate ingestion of psychoactive drugs. Later we learned that the patient's husband was also receiving thioridazine. Thioridazine, measured by HPLC-UV and FL, in a blood sample drawn from the patient on day 4 was 1.48 µg ml−1 (therapeutic levels for our laboratory are up to 2 µg dl−1). No haloperidol or risperidone was detectable in the same sample. In the literature there are several reports of Brugada-like ECG abnormalities during tryciclic antidepressant intoxication [1, 2], but such abnormalities have not been reported during neuroleptic overdose.

A fatal case of hyperthermia due to tricyclic antidepressant intoxication.

We report here an autopsy case of a 49-year-old woman with depression who died of hyperthermia, probably due to amitriptyline intoxication. She was found dead in bed with several empty amitriptyline pill containers. Her rectal temperature was 41.5 degrees C approximately 3 hours after death. Plasma levels of amitriptyline and nortriptyline were 0.51 and 0.74 mg/l, respectively. Possible mechanisms of fatal hyperthermia are discussed.

Is there a Role for Hemoperfusion/Hemodialysis as a Treatment Option in Severe Tricyclic Antidepressant Intoxication?

Suicidal self-poisoning with tricyclic antidepressants like doxepin is a major therapeutic problem in emergency medicine with a high fatality rate. Deaths are mainly caused by cardiotoxicity with arrhythmias, intraventricular conduction disturbances and myocardial depression. For treatment, alkalinization and hypertonic saline are recommended. The role of extracorporeal, treatment procedures is not clear. The possible benefit of hemoperfusion/hemodialysis is discussed in a case report with respect to the published literature. After ingestion of an amount of at least 5000 mg doxepin a 37-year-old man with endogenous depression developed cardiac arrest. After preclinical resuscitation with prolonged external cardiac massage, he was admitted to the intensive care unit with persistently severe hypotension and wide QRS complexes (230-260 ms). Despite fluid load, alkalinization, hypertonic saline and high-dose vasoactive substances the patient's condition did not improve. Hemoperfusion over hemoresin combined with hemodialysis led to an impressive clinical improvement with shortening of QRS duration (from 230 to 120 ms) and hemodynamic stabilization. The patient fully recovered without neurologic deficits. We report a successful treatment with hemoperfusion over hemoresin and hemodialysis in a patient with life-threatening doxepin poisoning intractable with the generally recommended treatment. In such acute TCA intoxication with severe cardiotoxicity, hemoperfusion/hemodialysis should be considered a potential treatment option, as the "toxicokinetics" of drugs may totally differ from their usual pharmacokinetic behaviour. Experimental and clinical studies are needed to clarify the toxicokinetics of TCA in order to improve the therapeutic approach.