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

INTRODUCTION: Gastric 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 PRESENTATION: Our 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. CONCLUSION: This 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.

An autopsy case of drowning under the influence of multiple psychotropic drugs.

A fatal case of drowning under the influence of multiple psychotropic drugs, such as quetiapine, escitalopram, aripiprazole and flunitrazepam, is presented. Quantitative toxicological analysis of a femoral blood sample revealed concentrations of quetiapine, escitalopram, aripiprazole and 7-aminoflunitrazepam (a metabolite of flunitrazepam) of 1.266 µg/ml, 0.609 µg/ml, 0.124 µg/ml and 0.055 µg/ml, respectively. From the autopsy findings, results of toxicological examination and investigation by the authorities, we concluded that the cause of death was drowning under the influence of mainly quetiapine and escitalopram.

Intravenous lipid emulsion-augmented plasma exchange in a rabbit model of clomipramine toxicity; survival, but no sink.

INTRODUCTION: Intravenous lipid emulsion (ILE) has been shown to ameliorate toxicity from lipophilic xenobiotics, attributed in part through sequestration to circulating lipid droplets (sink). We postulated additional benefit with plasma exchange therapy undertaken subsequent to lipid injection, hypothesising enhanced blood carriage of lipophilic toxin to increase yield when combined with an extracorporeal method of elimination. METHODS: Instrumented rabbits underwent clomipramine infusion at 3.2 mg/kg/min to target mean arterial pressure (MAP) of 50% baseline, then continuously at 2 mg/kg/min to death or 90 min. Resuscitation with saline (Control), sodium bicarbonate (BIC), ILE, or lipid emulsion plus cycled plasma exchange (LEPE), was commenced on attaining target MAP. RESULTS: Greater survival was observed in animals receiving lipid emulsion from both LE and LEPE groups (Control median 12.0 [IQR 10.5 ­ 20] min, BIC median 30 [IQR 19 ­ 33] min, LE 85 [IQR 30 ­ 90] min, LEPE 90 min; P 0.0001). No difference was observed in MAP, Heart Rate, or Electrocardiograph QRS duration between surviving LE and LEPE animals at 90 min. Mean plasma exchange of 52%circulating plasma volume returned only 0.04% of the administered clomipramine load in LEPE group animals. CONCLUSIONS: Infusion of lipid emulsion resulted in greater survival in this rabbit model of intravenous clomipramine toxicity. Plasma exchange performed in conjunction with administration of lipid emulsion failed to result in significant extracorporeal clomipramine elimination. Intravascular lipid sequestration of clomipramine appears an inadequate sole explanation for the beneficial effects of lipid emulsion.

Rhabdomyolysis as a manifestation of clomipramine poisoning.

CONTEXT: Tricyclic antidepressive agents are widely used in suicide attempts and present a variety of deleterious effects. Rhabdomyolysis is a rare complication of such poisoning. CASE REPORT: A 55-year-old woman ingested 120 pills of 25 mg clomipramine in a suicide attempt two days before admission. After gastric lavage in another emergency department on the day of intake, 80 pills were removed. On admission to our department, she was disoriented, complaining of a dry mouth and tremors at the extremities. An electrocardiogram showed a sinus rhythm with narrow QRS complexes. Laboratory results showed high creatine phosphokinase (CK = 15,094 U/l on admission; normal range = 26 to 140 U/l), hypocalcemia, slightly increased serum transaminases and mild metabolic acidosis. The patient's medical history included depression with previous suicide attempts, obsessive-compulsive disorder, hypothyroidism and osteoporosis. She presented cardiac arrest with pulseless electric activity for seven minutes and afterwards, without sedation, showed continuous side-to-side eye movement. She developed refractory hypotension, with need for vasopressors. Ceftriaxone and clindamycin administration was started because of a hypothesis of bronchoaspiration. The patient remained unresponsive even without sedation, with continuous side-to-side eye movement and a decerebrate posture. She died two months later. Rhabdomyolysis is a very rare complication of poisoning due to tricyclic drugs. It had only previously been described after an overdose of cyclobenzaprine, which has a toxicity profile similar to tricyclic drugs. CONCLUSIONS: Although arrhythmia is the most important complication, rhabdomyolysis should be investigated in cases of clomipramine poisoning.

Suicidal overdose with relapsing clomipramine concentrations due to a large gastric pharmacobezoar.

The paper presents a case of fatal intoxication after massive sustained-release clomipramine overdosage with prolonged toxicity related to a large gastric pharmacobezoar. 42-year-old female was admitted to the toxicology unit 14 h after drugs ingestion. At admission patient was deeply unconscious, required controlled mechanical ventilation. Serum total level of TCAs was 1955 ng/mL. Gastric lavage revealed no pills. Within the next 12h the patient's clinical condition improved. TCAs level decreased to 999 ng/mL. However, after another 10h the clinical condition started deteriorating again and the patient went into a deep coma requiring controlled mechanical ventilation. TCAs level increased to 2011 ng/mL. X-ray and computed tomography revealed large pharmacobezoar consisted from radio-opaque pills. In the 28th h of hospitalization gastrotomy was performed, confirming presence of pharmacobezoar formed from Anafranil SR tablets. After surgery TCAs level was gradually decreasing. However, the patient's condition did not improve, she died 32 h after gastrotomy. Post-mortem analyses revealed drug and its metabolite toxic levels in blood (clomipramine - 1729 ng/mL, norclomipramine - 431 ng/mL) and toxic levels in internal organs: myocardium (clomipramine - 14,420 ng/g, norclomipramine - 35,930 ng/g), vitreous humor (clomipramine - 1000 ng/mL, norclomipramine - 3110 ng/mL). Described case report indicates that sustained release clomipramine tablets may form pharmacobezoar. X-ray and computed tomography examinations should be considered in cases of massive abuse of sustained release clomipramine, particularly if symptoms of intoxication are recurrent or persistent.

Rhabdomyolysis as a manifestation of clomipramine poisoning / Rabdomiolise como manifestacao de intoxicacao por clomipramina

CONTEXT: Tricyclic antidepressive agents are widely used in suicide attempts and present a variety of deleterious effects. Rhabdomyolysis is a rare complication of such poisoning. CASE REPORT: A 55-year-old woman ingested 120 pills of 25 mg clomipramine in a suicide attempt two days before admission. After gastric lavage in another emergency department on the day of intake, 80 pills were removed. On admission to our department, she was disoriented, complaining of a dry mouth and tremors at the extremities. An electrocardiogram showed a sinus rhythm with narrow QRS complexes. Laboratory results showed high creatine phosphokinase (CK = 15,094 U/l on admission; normal range = 26 to 140 U/l), hypocalcemia, slightly increased serum transaminases and mild metabolic acidosis. The patient's medical history included depression with previous suicide attempts, obsessive-compulsive disorder, hypothyroidism and osteoporosis. She presented cardiac arrest with pulseless electric activity for seven minutes and afterwards, without sedation, showed continuous side-to-side eye movement. She developed refractory hypotension, with need for vasopressors. Ceftriaxone and clindamycin administration was started because of a hypothesis of bronchoaspiration. The patient remained unresponsive even without sedation, with continuous side-to-side eye movement and a decerebrate posture. She died two months later. Rhabdomyolysis is a very rare complication of poisoning due to tricyclic drugs. It had only previously been described after an overdose of cyclobenzaprine, which has a toxicity profile similar to tricyclic drugs. CONCLUSIONS: Although arrhythmia is the most important complication, rhabdomyolysis should be investigated in cases of clomipramine poisoning. .

CONTEXTO: Antidepressivos tricíclicos são amplamente utilizados em tentativas de suicídio e apresentam diversos efeitos deletérios, sendo a rabdomiólise uma complicação rara dessa intoxicação. RELATO DO CASO: Uma mulher de 55 anos ingeriu 120 comprimidos de clomipramina de 25 mg numa tentativa de suicídio dois dias antes da admissão. Após lavagem gástrica em outro serviço de urgência no dia da ingestão, 80 comprimidos foram retirados. Na admissão em nosso serviço, a paciente estava desorientada, queixando-se de boca seca e tremores de extremidades. O eletrocardiograma mostrou ritmo sinusal com complexos QRS estreitos. Exames laboratoriais evidenciaram aumento de creatinofosfoquinase (CK = 15.094 U/L na admissão; intervalo da normalidade = 26 a 140 U/L), hipocalcemia, discreto aumento das transaminases e leve acidose metabólica. Antecedentes pessoais incluíam depressão com tentativas de suicídio prévias, transtorno obsessivo compulsivo, hipotireoidismo e osteoporose. A paciente apresentou parada cardiorrespiratória com atividade elétrica sem pulso por sete minutos e, posteriormente, sem sedação, foi observado olhar em varredura. A paciente evoluiu com hipotensão refratária, necessitando de vasopressores. Ceftriaxone e clindamicina foram iniciados pela hipótese de broncoaspiração. A paciente permaneceu irresponsiva mesmo sem sedação, com olhar em varredura contínuo e postura descerebrada. A paciente evoluiu para óbito dois meses após. Rabdomiólise é uma complicação rara da intoxicação por tricíclicos, e só foi descrita em overdose de ciclobenzaprina, a qual tem um perfil de toxicidade semelhante aos tricíclicos. CONCLUSÕES: Apesar de as arritmias serem as complicações mais temidas, ...

A fatal case of potential chronic overdoses of prescribed and proprietary remedies.

A 33-year-old man was found in a state of cardiopulmonary arrest. He was transported to an emergency hospital but was pronounced dead. He had suffered from depression for about 8 years and had attempted suicide repeatedly. A search by the police found 645 empty Press Through Package (PTP) sheets. They had included neuroleptics, antidepressants, hypnotics, proprietary antitussives containing caffeine, proprietary cold remedies containing caffeine, and other unidentified drugs. An autopsy showed higher rectal temperature (38 degrees C), severe pulmonary edema (left: 681 g, right: 821 g), and a large amount of urine in the bladder (about 760 mL). Toxicological analyses using gas chromatography-mass spectrometry (GC/MS) and high performance liquid chromatography (HPLC) demonstrated that doses of clomipramine hydrochloride (a tricyclic antidepressant), chlorpromazine (a phenothiazine), and caffeine (a methylxanthine derivative) were within the toxic range (0.68, 0.64, and 34.24 [microg/mL], respectively). Histological examination showed centrilobular necrosis of the liver with small fat droplets. We concluded that he had died of pulmonary edema due to combined drug intoxication including proprietary antitussives and cold remedies. Furthermore, there was a strong possibility that he had habitually taken overdoses of those drugs. Herein, the risk of misuse of prescribed and proprietary drugs, especially for people with psychological problems, should be reemphasized.

Forensic toxicological implication of an autopsy case of mixed drug overdose involving clomipramine, chlorpromazine and flunitrazepam.

A case of fatal poisoning involving clomipramine, chlorpromazine and flunitrazepam is presented. Quantitative toxicological analysis showed that the concentrations of clomipramine, chlorpromazine and 7-aminoflunitrazepam (a metabolite of flunitrazepam) in the femoral blood were 3.24 microg/ml, 0.36 Kg/ml and 0.61 microg/ml, respectively, and large amounts of drugs were also detected from the stomach contents. We concluded that the cause of death was due to the combined use of clomipramine, chlorpromazine and flunitrazepam.

Endoscopic removal of slow release clomipramine bezoars in two cases of acute poisoning.

INTRODUCTION: Acute gastroscopy is seldom advocated in cases of drug overdose. However, this intervention is sometimes recommended in cases where a pharmacobezoar of toxic tablets has formed. CASE REPORTS: We describe two patients who were admitted after major ingestion of slow release clomipramine. In one case an abdominal x-ray was highly suspicious of a large pharmacobezoar in the stomach and in the other case a tablet conglomerate totally obstructed the oesophagus. Both conditions were successfully managed by acute gastroscopy. DISCUSSION: There are limited and inconclusive recommendations in the literature concerning the optimal treatment of pharmacobezoars. CONCLUSION: This article provides further evidence that slow release clomipramine may be capable of forming a radio-opaque pharmacobezoar. The clinical courses in these two cases suggest that tablet removal by gastroscopy should be considered in selected cases of drug poisoning. Suspicion of a pharmacobezoar may warrant diagnostic investigations such as imaging studies and endoscopy.

A fatal clomipramine intoxication case of a chronic alcoholic patient: application of postmortem hair analysis method of clomipramine and ethyl glucuronide using LC/APCI/MS.

Toxicological investigations of postmortem specimens of a 26-year-old man were performed with the use of LC/APCI/MS. They revealed in the blood of the deceased clomipramine (9.49 microg/g) and its main metabolite norclomipramine (1.10 microg/g) at concentrations explaining the fatal outcome. The presence of these xenobiotics in a 12-cm-long strand of hair (clomipramine, 7.60 ng/mg in I segment; 4.19 ng/mg in II segment; 1.86 ng/mg in III segment; norclomipramine, 5.71 ng/mg in I segment; 9.71 ng/mg in II segment; 4.13 ng/mg in III segment) confirmed the fact obtained from the medical history that the deceased had been receiving clomipramine as an antidepressant for 1 year prior to his death. The analysis demonstrated ethanol in autopsy blood (2.5mg/ml) and urine (3.2mg/ml); ethyl glucuronide as a marker of chronic alcohol abuse was detected in the deceased's hair (0.44 ng/mg in I segment; 0.07 ng/mg in II segment; n.d. in III segment). These findings may suggest the contribution of alcohol in the mechanism of drug-ethanol interaction, which in consequence might have affected the biotransformation of clomipramine in the final period of his life and evoked the ultimate toxic effect.

Two cases involving clomipramine intoxication.

Clomipramine and its active metabolite norclomipramine were identified and quantitated in multiple tissues recovered from two postmortem cases using liquid chromatography-mass spectrometry. In both cases clomipramine toxicity was assessed primarily upon levels determined from brain samples. This communication supplements the database on clomipramine and norclomipramine by providing quantitative determinations of both parent drug and metabolite in multiple tissues. A literature search revealed a paucity of data on clomipramine and norclomipramine levels in general and a total absence of documented brain levels. In patients who have undergone long-term tricyclic antidepressant (TCA) therapy, blood and liver analysis alone may not be sufficient to establish toxicity. Such patients can sequester substantial amounts in liver, a concern because the TCAs are subject to significant postmortem redistribution. When conducting postmortem investigations, the inclusion of brain determination provides valuable information in assessing the magnitude of toxicity in cases involving clomipramine and its active metabolite norclomipramine.

Ping-pong gaze in combined intoxication with tranylcypromine, thioridazine, and clomipramine.

OBJECTIVE: This paper reports the occurrence of ping-pong gaze, a neuro-ophthalmological syndrome usually related to severe structural brain damage, in a patient intoxicated with tranylcypromine, thioridazine, and clomipramine. BACKGROUND: Although there have been some reports about the occurence of Ping-pong gaze after intoxications, it is usually related to severe bilateral hemispheric brain damage following stroke or traumatic injuries. METHOD: We report the case of a 56-year old woman who developed a neurotoxic syndrome with coma, hyperthermia, muscular rigidity, myoclonic jerks and tachycardia following an intoxication. Additionally rhythmic and pendular conjugate horizontal eye movements could be observed for three days, so that the diagnosis of ping-pong gaze was made. RESULTS: A treatment with dantrolene lead to complete remission of the neurotoxic syndrome with no signs of neurological or physical deficits. At the stage of regaining consciousness the eye movements became normal. CONCLUSION: In our case the combined intoxication with an monoamine oxidase inhibitor, a neuroleptic and a tricyclic agent lead to a neurotoxic syndrome and the occurrence of a rare neuro-ophthalmological syndrome usually related to bilateral hemispheric brain dysfunction.

Radiopacity of clomipramine conglomerations and unsuccessful endoscopy: report of 4 cases.

BACKGROUND: The radiopacity of ingested substances may serve as a clue to the presence of particular compounds, as this characteristic varies considerably among medications and household products. Tablet conglomerations are also variably radiopaque. We report 4 cases of clomipramine poisoning associated with formation of radiopaque masses, believed to be clomipramine, in the area of the stomach. CASE REPORTS: Four patients were admitted to the Toxicological Intensive Care Unit after ingestions of, respectively, 8.5 g (180 tablets of mixed strength), 7.5 g (100 tablets), 10.5 g (140 tablets), and 4.5 g (60 tablets) of clomipramine, along with other sedatives and antipsychotics. In each case, a rounded density was observed in the gastric area on plain chest radiograph. The hospital courses of each patient were marked by tachycardia, hypotension, QRS and QT prolongation, seizures, and decreased mental status. Three of 4 patients underwent unsuccessful endoscopy to remove tablet fragments and subsequently suffered gastrointestinal hemorrhage requiring transfusion. All patients were discharged recovered from the hospital. DISCUSSION: Clomipramine, a potent tricyclic antidepressant, has been previously reported to be nonradiopaque, and has not been reported to induce formation of concretions. These cases suggest that massive ingestions of clomipramine may form bezoars which are radiopaque and may be associated with serious toxicity. Careful consideration should be given prior to the use of gastric endoscopy for the retrieval of tablet fragments since significant hemorrhage, attributed to the procedure itself rather than to clomipramine toxicity, may ensue.

Among fatal poisonings dextropropoxyphene predominates in younger people, antidepressants in the middle aged and sedatives in the elderly.

To compare the characteristics of dextropropoxyphene (DXP) poisoning victims with those of victims of poisonings by antidepressants and sedatives, we examined all fatal poisonings due to DXP, antidepressants or sedatives among autopsies performed at one department of forensic medicine in Sweden during the six-year period from 1992 to 1997. In 202 cases, death was classified as fatal poisonings by DXP, antidepressants or sedatives. DXP caused death in 78 cases (39%), antidepressants in 49 (24%), and sedatives in 75 (37%). DXP as a single preparation was predominant in causing death. The second compound, flunitrazepam, caused death in 30 cases (15%). The victims of poisonings by DXP, antidepressants, or sedatives shared a similar history of alcohol/drug abuse, depression and somatic illness. They were mostly living alone at the time of death (>60%), the majority died at home (81%), and suicide was the most frequent manner of death (73%). Age seemed to be an important characteristic regarding the choice of drug. Younger people predominantly died of DXP (mean age 43 years, 95% confidence interval, CI 39-47), and elderly people of sedatives (mean age 59 years, CI 55-63). Antidepressants were found mainly in middle-aged victims (mean age 51 years, CI 48-54). The predominance of sedatives among the elderly might be explained by a very high prescription rate of such drugs in older age groups, but prescription rate could not explain the DXP predominance among younger people. We hypothesize that younger people are more prone to abuse therapeutic drugs for euphoric reasons than elderly people, and that because of its high toxicity, DXP leads to accidental deaths more often than sedatives.

Serotonin syndrome due to an overdose of moclobemide and clomipramine. A potentially life-threatening association.

The serotonin syndrome is frequently characterized by minor neurologic manifestations that regress rapidly (such as confusion, tremor, ...). Many medications including tricyclic antidepressants, serotonin reuptake inhibitors, tryptophan and the association of monoamine oxidase inhibitors together with a serotoninergic agent have been implicated in this syndrome. In certain cases, and for poorly understood reasons, clinical manifestations can include circulatory collapse, malignant hyperthermia, convulsions and rhabdomyolysis. These forms are often fatal. Treatment, other than the withdrawal of the offending drug, is symptomatic. Dialysis may be of value in withdrawing the drug from the circulatory system. We report a patient with the serotonin syndrome of favorable outcome due to an overdose of moclobemide and clomipramine.

Three suicide attempts with moclobemide.

OBJECTIVE: To report plasma moclobemide, course and outcome of two cases of overdose with moclobemide alone and one case of combined ingestion of moclobemide and clomipramide. METHODS: Moclobemide identification and quantification was achieved by gas chromatography-mass spectrometry after alkaline extraction. CASE REPORTS: In case 1, plasma moclobemide was 2.8 mg/L with 1.8 mg/L clomipramide; in case 2, 18 mg/L; in case 3 60.9 mg/L and 4.6 mg/L 12 hours later. None of the patients showed serious effects during 24 hours of observation. Plasma moclobemide at 10 to 30 times therapeutic was not associated with major toxic effects. Moclobemide seems to be considerably less toxic than tricyclic antidepressants.