Asunto(s)
Antidepresivos de Segunda Generación/envenenamiento , Puente Cardiopulmonar , Sobredosis de Droga/etiología , Sobredosis de Droga/terapia , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/cirugía , Intento de Suicidio , Clorhidrato de Venlafaxina/envenenamiento , Adolescente , Descontaminación/métodos , Electrocardiografía , Femenino , Lavado Gástrico , Humanos , Síndrome de QT Prolongado/diagnóstico , Convulsiones/inducido químicamenteRESUMEN
ABSTRACT: The authors present here a case of a pharmacobezoar after drug overdose, diagnosed using multiple blood samples for TDM. This grand round highlights the importance of a dialog between a clinician and a TDM consultant for the optimal care of a patient.
Asunto(s)
Bezoares , Sobredosis de Droga , Oxazepam/envenenamiento , Clorhidrato de Venlafaxina/envenenamiento , Bezoares/diagnóstico , Sobredosis de Droga/diagnóstico , Humanos , Rondas de EnseñanzaRESUMEN
Background: The optimal observation time period with respect to seizures after venlafaxine overdose is unclear. We conducted a 10-year retrospective review of calls to the California Poison Control System to describe the time of onset of seizures in adult and pediatric overdose of venlafaxine.Methods: Inclusion criteria included adult and pediatric patients with exposure to venlafaxine, who were admitted to a health care facility and who had at least one seizure. We did not exclude cases in which co-ingestions of other drugs were reported. Data extraction of a priori defined variables was recorded. Descriptive statistics were used to characterize the cohort of patients, including means, medians, and interquartile ranges.Results: The total number of cases included in the data analysis was 123 (12.9% of all venlafaxine ingestions). The longest time to last seizure was 24 h. Twenty-five percent of participants had a seizure from hour 7 to 24 h. This did not differ significantly between IR and XR formulations.Conclusions: Optimal observation time with respect to seizures after overdose of immediate-release formulation of venlafaxine is 18 h (24 h if ingested with other medications), and 21 h for patients who are poisoned with the sustained-release formulation.
Asunto(s)
Antidepresivos de Segunda Generación/envenenamiento , Sobredosis de Droga/complicaciones , Convulsiones/inducido químicamente , Clorhidrato de Venlafaxina/envenenamiento , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Centros de Control de Intoxicaciones , Estudios Retrospectivos , Adulto JovenRESUMEN
Background: Venlafaxine use to achieve an amphetamine-like high has been described but data regarding the epidemiology and clinical effects are sparse. Objectives: Describe the prevalence and toxicity of venlafaxine abuse reported to US poison control centers. Methods: This was a retrospective review of venlafaxine exposures reported to the National Poison Data System (NPDS) from 2000 to 2016. Inclusion criteria were: age 12 years and older, reason for exposure intentional-abuse, and either single-substance exposure or venlafaxine was the first substance. The primary outcome was prevalence of intentional-abuse of venlafaxine. Secondary outcomes characterized demographics, geographic distribution, toxicity, and outcomes. Results: Intentional-abuse accounted for 752 of 85,621 venlafaxine exposures. Overall prevalence was 87.8 intentional-abuse exposures/10,000 venlafaxine exposures reported to NPDS (range, 59.3-117.6/10,000). Prevalence decreased from 107/10,000 in 2000 to 59.3/10,000 in 2016. Median age was 23 years and 50% were female. Primary route was ingestion (90.8%) with 4.7% using venlafaxine via inhalation/intranasal insufflation, and 3.7% both routes. There were 227 venlafaxine-only exposures; 54.0% were treated/released from the emergency department, 20% were admitted for medical management, 9.0% to a psychiatric facility, and 17.0% managed at home. Known medical outcomes for single-substance exposures were: no effect (24.0%), minor (39.0%), moderate (33.0%), and major (4.0%); no deaths occurred. Most frequent clinical effects were tachycardia (33.9%), drowsiness (20.7%), and agitation (11.5%). Conclusion: The prevalence of venlafaxine abuse reported to poison control centers has decreased. Medical outcomes are usually not serious. Clinicians should be aware that non-medical use is possible but infrequently reported to poison control centers.
Asunto(s)
Centros de Control de Intoxicaciones/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Clorhidrato de Venlafaxina/envenenamiento , Adolescente , Adulto , Femenino , Humanos , Masculino , Prevalencia , Estudios Retrospectivos , Estados Unidos , Adulto JovenRESUMEN
Drugs for the treatment of depressive disorders, including SNRIs (serotonin noradrenaline reuptake inhibitors) venlafaxine and duloxetine, are widely prescribed as they have a high therapeutic to toxicity ratio. In rare cases, adverse effects may be severe, usually due to iatrogenic, accidental or intentional self-overdose that cause the excessive accumulation of serotonin and noradrenaline in synaptic clefts. Lethal intoxication with a combination of venlafaxine and duloxetine (postmortem blood concentrations 24 mg/L and 0.97 mg/L, respectively) without co-ingested substances, comorbidities or injuries that could have an unknown contribution to a fatal outcome is presented for the first time in the following case report, with a comprehensive clinical history, and complete results of the performed analyses. The cause of death was a serotonin syndrome that progressed to death in approximately six hours and 15 min after the suicidal ingestion of venlafaxine and duloxetine. Despite the high therapeutic to toxicity ratio SNRIs, which are reserved for patients with severe forms of depressive disorders and a higher suicidal tendency, they should be cautiously prescribed and handed over in smaller packages to make them easier to follow, and thus avoid accumulation within the patient's reach.
Asunto(s)
Clorhidrato de Duloxetina/envenenamiento , Síndrome de la Serotonina/inducido químicamente , Inhibidores de Captación de Serotonina y Norepinefrina/envenenamiento , Clorhidrato de Venlafaxina/envenenamiento , Adulto , Sobredosis de Droga , Clorhidrato de Duloxetina/análisis , Femenino , Humanos , Inhibidores de Captación de Serotonina y Norepinefrina/análisis , Suicidio , Clorhidrato de Venlafaxina/análisisRESUMEN
Methoxetamine, 3-methoxyphencyclidine or 3-methoxyeticyclidine are arylcyclohexylamines which have been abused in the past. However, the market for new psychoactive substances, in particular for research chemicals, is rapidly growing and new compounds are being regularly explored by users. Abuse can lead to clinical case and in the worst-case scenario to fatalities. We present the fatal case of a 52-year-old man, who was found dead in the bedroom by his fiancé. He had abused N-ethyldeschloroketamine and venlafaxine prior to his death. These compounds were retrieved from a non-targeted gas chromatography/mass spectrometry-based screening approach of a purified urine sample. In addition, deschloroketamine, bisoprolol and ramiprilate were found in the urine sample, but were either absent or only present at low level in femoral blood. During autopsy a number of tablets were found in the duodenum and identified as venlafaxine. Furthermore, N-ethyldeschloroketamine was quantified in various specimens taken during autopsy and the highest concentration was observed in liver (6,137 ng/g) followed by urine (3,468 µg/L), bile fluid (3,290 µg/L), gastric contents (3,086 µg/L), heart blood (2,159 µg/L) and liquor (1,564 µg/L). The smallest amount was found in femoral blood (375 µg/L). N-ethyldeschloroketamine was also found in the disposable syringes, in a beaker and on the spatula along with deschloroketamine, morphine, metamizole, oxycodone, flupirtin or ibuprofen. The concentrations presented-in particular for femoral blood-are a good starting point for evaluating N-ethyldeschloroketamine intoxications in the future. The other values are helpful for evaluating the post-mortem concentration distribution of this research chemical.
Asunto(s)
Sobredosis de Droga/orina , Toxicología Forense/métodos , Drogas Ilícitas/orina , Ketamina/análogos & derivados , Detección de Abuso de Sustancias/métodos , Clorhidrato de Venlafaxina/orina , Resultado Fatal , Cromatografía de Gases y Espectrometría de Masas , Humanos , Drogas Ilícitas/envenenamiento , Ketamina/envenenamiento , Ketamina/orina , Masculino , Persona de Mediana Edad , Clorhidrato de Venlafaxina/envenenamientoRESUMEN
We describe a young patient who ingested 18 g (240 times the daily therapeutic dose) of venlafaxine in a suicide attempt. She developed severe cardiomyopathy in a takotsubo distribution causing cardiogenic shock and multi-organ dysfunction syndrome (MODS). She was successfully treated with intravenous lipid emulsion (ILE), extracorporeal life support (ECLS) and CytoSorb®. This is remarkable as, to the best of the authors' knowledge, this is the highest amount of venlafaxine intake seen in the literature with a nonfatal outcome.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Emulsiones Grasas Intravenosas/uso terapéutico , Hemofiltración/métodos , Inhibidores de Captación de Serotonina y Norepinefrina/envenenamiento , Cardiomiopatía de Takotsubo/terapia , Clorhidrato de Venlafaxina/envenenamiento , Femenino , Humanos , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/terapia , Choque Cardiogénico/etiología , Choque Cardiogénico/terapia , Intento de Suicidio , Cardiomiopatía de Takotsubo/etiología , Adulto JovenRESUMEN
Venlafaxine is a selective serotonin noradrenaline reuptake inhibitor and commonly prescribed antidepressant in adults. Most patients overdosing with venlafaxine develop only mild symptoms. Severe toxicity is reported with the most common symptoms being CNS depression, serotonin toxicity, seizure, or cardiac conduction abnormalities. However, lactic acidosis is an uncommon adverse effect. Here, we present the first case in the literature reporting lactic acidosis due to venlafaxine overuse in an adolescent.
Asunto(s)
Acidosis Láctica/inducido químicamente , Inhibidores Selectivos de la Recaptación de Serotonina/envenenamiento , Clorhidrato de Venlafaxina/envenenamiento , Acidosis Láctica/tratamiento farmacológico , Adolescente , Sobredosis de Droga/tratamiento farmacológico , Femenino , HumanosRESUMEN
BACKGROUND: A number of researchers have speculated that neurological disorders are mostly due to the interaction of common susceptibility genes with environmental, epigenetic and stochastic factors. Genetic factors such as mutations, insertions, deletions and copy number variations (CNVs) are responsible for only a small subset of cases, suggesting unknown environmental contaminants play a role in triggering neurological disorders like idiopathic autism. Psychoactive pharmaceuticals have been considered as potential environmental contaminants as they are detected in the drinking water at very low concentrations. Preliminary studies in our laboratory identified gene sets associated with neuronal systems and human neurological disorders that were significantly enriched after treating fish brains with psychoactive pharmaceuticals at environmental concentrations. These gene expression inductions were associated with changes in fish behavior. Here, we tested the hypothesis that similar treatments would alter in vitro gene expression associated with neurological disorders (including autism) in human neuronal cells. We differentiated and treated human SK-N-SH neuroblastoma cells with a mixture (fluoxetine, carbamazepine and venlafaxine) and valproate (used as a positive control to induce autism-associated profiles), followed by transcriptome analysis with RNA-Seq approach. RESULTS: We found that psychoactive pharmaceuticals and valproate significantly altered neuronal gene sets associated with human neurological disorders (including autism-associated sets). Moreover, we observed that altered expression profiles in human cells were similar to gene expression profiles previously identified in fish brains. CONCLUSIONS: Psychoactive pharmaceuticals at environmental concentrations altered in vitro gene expression profiles of neuronal growth, development and regulation. These expression patterns were associated with potential neurological disorders including autism, suggested psychoactive pharmaceuticals at environmental concentrations might mimic, aggravate, or induce neurological disorders.
Asunto(s)
Trastorno Autístico/genética , Contaminantes Ambientales/envenenamiento , Enfermedades del Sistema Nervioso/genética , Psicotrópicos/envenenamiento , Transcriptoma/efectos de los fármacos , Animales , Carbamazepina/envenenamiento , Línea Celular Tumoral , Fluoxetina/envenenamiento , Perfilación de la Expresión Génica/métodos , Humanos , Neuroblastoma/genética , Neuroblastoma/patología , Transcriptoma/genética , Ácido Valproico/envenenamiento , Clorhidrato de Venlafaxina/envenenamientoRESUMEN
Venlafaxine is a serotonergic and noradrenergic antidepressant. It shares the same serotonergic adverse effects as the "selective" serotonin reuptake inhibitor (SSRI) antidepressants while in addition provoking noradrenergic adverse effects, in particular cardiovascular disorders, yet offers no demonstrated advantages over SSRIs in terms of efficacy. Several cohort studies using data from a UK database have shown that venlafaxine overdoses are more frequently fatal than SSRI overdoses. Several meta-analyses of more than 70 published and unpublished randomised clinical trials, including about 7000 patients in total, have shown that treatment discontinuation due to adverse effects is more common with venlafaxine than with SSRI antidepressants. Venlafaxine can provoke dose-dependent blood pressure elevation, sometimes requiring treatment discontinuation. Exposure to venlafaxine during the second and third trimesters of pregnancy increases the risk of pre-eclampsia and eclampsia. A cohort study in about 50 elderly patients and analysis of several hundred reported suicide attempts by venlafaxine overdose demonstrated a risk of QT interval prolongation, which can lead to torsades de pointes, an unusual and potentially fatal type of ventricular tachycardia. Large British and Danish cohort studies found no increased risk of sudden cardiac death with venlafaxine compared with other antidepressants. However, since only 3.5% and 7% of the patients were using venlafaxine, the statistical power of these studies was relatively low. In practice, the data available as of mid-2015 from clinical trials and epidemiological studies confirm the harms foreseeable from venlafaxine's pharmacological properties: a higher risk of cardiovascular adverse effects and of fatal overdoses than with most SSRI antidepressants. Since venlafaxine and SSRI antidepressants have similar and limited efficacy, venlafaxine is best avoided. An SSRI anti-depressant is a more reasonable option, with the exception of citalopram and escitalopram which also expose patients to more cardiovascular adverse effects.
Asunto(s)
Trastorno Depresivo/tratamiento farmacológico , Hipertensión/inducido químicamente , Síndrome de QT Prolongado/inducido químicamente , Preeclampsia/inducido químicamente , Inhibidores de Captación de Serotonina y Norepinefrina/efectos adversos , Torsades de Pointes/inducido químicamente , Clorhidrato de Venlafaxina/efectos adversos , Relación Dosis-Respuesta a Droga , Sobredosis de Droga/mortalidad , Femenino , Humanos , Embarazo , Clorhidrato de Venlafaxina/envenenamientoAsunto(s)
Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/cirugía , Intento de Suicidio , Abdomen/diagnóstico por imagen , Anciano , Endoscopía Gastrointestinal , Humanos , Masculino , Fenotiazinas/envenenamiento , Radiografía Abdominal , Tomografía Computarizada por Rayos X , Clorhidrato de Venlafaxina/envenenamientoRESUMEN
OBJECTIVES: Venlafaxine overdose can lead to cardiovascular collapse that is difficult to resuscitate with traditional Advanced Cardiovascular Life Support protocols. Evidence has suggested that lipid emulsion infusion therapy has been successful in the treatment of antidepressant overdose. No studies have determined the optimal combination of lipid/advanced cardiovascular life support therapy for treatment. METHODS: This study was a prospective, experimental, between subjects design with a swine model investigating the effectiveness of drug combinations administered with cardiopulmonary resuscitation (CPR) postvenlafexine overdose. Subjects were randomly assigned to 1 of eight groups containing seven subjects. The groups tested were CPR only and CPR with epinephrine alone; vasopressin alone; lipid alone; epinephrine and vasopressin; epinephrine and lipid; vasopressin and lipid; and epinephrine, vasopressin, and lipid. The outcomes of interest were survival odds and time to return of spontaneous circulation. RESULTS: Results on these swine models indicate that the use of vasopressin coupled with lipids for venlafaxine overdose resulted in a higher survival rate when compared to the control group (p = 0.023). Groups receiving vasopressin experienced statistically faster times to return of spontaneous circulation than other groups (p = 0.019). CONCLUSIONS: The results suggest that in swine models, the optimal treatment for venlafaxine overdose would include vasopressin with lipids.
Asunto(s)
Reanimación Cardiopulmonar , Emulsiones Grasas Intravenosas/uso terapéutico , Inhibidores de Captación de Serotonina y Norepinefrina/envenenamiento , Vasoconstrictores/uso terapéutico , Vasopresinas/uso terapéutico , Clorhidrato de Venlafaxina/envenenamiento , Animales , Reanimación Cardiopulmonar/métodos , Sobredosis de Droga/mortalidad , Sobredosis de Droga/terapia , Quimioterapia Combinada , Epinefrina/uso terapéutico , Humanos , Masculino , Oportunidad Relativa , Estudios Prospectivos , Distribución Aleatoria , Tasa de Supervivencia , PorcinosRESUMEN
Lactic acidosis that is not secondary to tissue hypoperfusion or hypoxemia (type B lactic acidosis) is a rare but potentially fatal condition that has been associated with drugs like metformin, linezolid, and nucleoside reverse-transcriptase inhibitors in patients with HIV. We report the first case of type B lactic acidosis caused by overdose of the serotonin-norepinephrine reuptake inhibitor, venlafaxine. A 55-year-old man with no significant medical history was brought to the emergency department after intentional ingestion of around 80 capsules of venlafaxine (a total dose of over 6000 mg) in an attempt to commit suicide. Complete blood count and comprehensive metabolic panel were unremarkable except for a bicarbonate level of 13 mEq/L and an anion gap of 22 mEq/L. An arterial blood gas revealed a pH of 7.39, partial pressure of CO2 of 19 mm Hg, calculated bicarbonate of 11.5 mEq/L, and a lactate level of 8.6 mmol/L. The patient was started on aggressive intravenous hydration with normal saline along with oral activated charcoal with sorbitol. Repeat laboratory work after 4 hours showed an improvement in anion gap (15 mEq/L) and serum lactate (5.6 mmol/L). The patient remained stable throughout the hospital stay and lactic acidosis resolved in 24 hours. In the absence of hypotension, hypoxemia, kidney or liver dysfunction, myopathy, malignancy, or use of other medications, venlafaxine was the most likely cause of lactic acidosis in our case. Rapid improvement of acidosis was probably related to clearance of the drug.
Asunto(s)
Acidosis Láctica/etiología , Sobredosis de Droga/complicaciones , Clorhidrato de Venlafaxina/envenenamiento , Acidosis Láctica/tratamiento farmacológico , Antídotos/uso terapéutico , Análisis de los Gases de la Sangre , Carbón Orgánico/uso terapéutico , Sobredosis de Droga/tratamiento farmacológico , Fluidoterapia , Humanos , Masculino , Persona de Mediana Edad , Sorbitol/uso terapéuticoRESUMEN
The prognosis of out-of-hospital cardiac arrest (OHCA) due to intoxication is dismal. Tricyclic antidepressants (TCAs) are widely used in the treatment of depression, but possess significant cardiotoxicity, and are one of the most common medications used in suicide attempts worldwide. TCA poisoning can cause hypotension, seizures, and cardiac conduction disturbances, which can lead to life-threatening arrhythmia. Current guidelines recommend mild therapeutic hypothermia (TH) for unconscious survivors of OHCA, but hypothermia treatment itself can cause disturbances in cardiac conduction, which could aggravate the effect of TCAs on cardiac conduction. We report the successful use of TH in a 19-year-old woman who was resuscitated from ventricular tachycardia after intentional ingestion of amitriptyline and venlafaxine, a serotonin-norepinephrine reuptake inhibitor. The cardiac arrest was witnessed, but no bystander cardiopulmonary resuscitation (CPR) was performed. The initial rhythm was ventricular tachycardia with no detectable pulse. Three defibrillations, magnesium sulfate, and sodium bicarbonate were given and her trachea was intubated, after which return of spontaneous circulation (ROSC) was achieved in 26 minutes. After ROSC, she had seizures and was sedated with propofol. Out-of-hospital TH was initiated with 1500 mL of cold Ringer's acetate. An infusion of norepinephrine was initiated for low blood pressure. On arrival at the university hospital, she was unconscious and had dilated pupils. She was tachycardic with a body temperature of 33.5°C. She was transferred to the intensive care unit and TH was maintained with invasive cooling. During the TH treatment, she did not experience any serious cardiac arrhythmia, transthoracic echocardiogram was normal, and the electrocardiogram (ECG) returned to normal. The patient was extubated 45 hours after the cardiac arrest. After the extubation, she was alert and cooperative, but slightly delusional. She was transferred to a ward on the third day and discharged from hospital on the sixth day of admission. Ambulatory psychiatric follow-up was organized. Neuropsychological examinations were later performed and she was estimated to be able to work at her previous job. This case report suggests that mild TH is safe even in case of intoxication with a drug known to cause serious cardiac conduction disturbances and arrhythmia.
Asunto(s)
Inhibidores de Captación Adrenérgica/envenenamiento , Amitriptilina/envenenamiento , Hipotermia Inducida/métodos , Soluciones Isotónicas/administración & dosificación , Paro Cardíaco Extrahospitalario/terapia , Inhibidores de Captación de Serotonina y Norepinefrina/envenenamiento , Clorhidrato de Venlafaxina/envenenamiento , Regulación de la Temperatura Corporal , Frío , Sobredosis de Droga , Electrocardiografía , Femenino , Humanos , Paro Cardíaco Extrahospitalario/inducido químicamente , Paro Cardíaco Extrahospitalario/diagnóstico , Paro Cardíaco Extrahospitalario/fisiopatología , Recuperación de la Función , Intento de Suicidio , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
An 18-year-old woman ingested 22 g of venlafaxine with suicidal attempt. At admittance two hours after ingestion she had serotonine syndrome, repeated seizures and hypotension. After eight hours malignant arrythmias culminated in cardiac arrest, which was successfully resuscitated. Progressive liver and cardiac failure lead to fatal outcome after 48 hours. It is discussed whether early lipid infusion should be given in case of ingestion of high doses of venlafaxine, before myoclonia, seizures, hypotension, rhabdomyolysis and liver failure developed, since these can only be treated symptomatically.