RESUMEN
BACKGROUND: Serotonin toxicity is a common cause of drug-induced altered mental status. However, data on the causes of serotonin toxicity, symptomatology, complications, and rate of antidotal treatment are limited. METHODS: This study evaluated cases of serotonin toxicity in the ToxIC registry, an international database of prospectively collected cases seen by medical toxicologists. Serotonin toxicity was diagnosed by bedside evaluation of medical toxicology specialists and explicit criteria were not used. The database was searched for "serotonin syndrome" between January 1, 2010, and December 31, 2016. RESULTS: There were 1010 cases included. Females made up 608 (60%) cases. Ages are as follows: younger than 2 years (3, 0.3%), 2 to 6 years (8, 0.8%), 7 to 12 years (9, 0.9%), 13 to 18 years (276, 27.3%), 19 to 65 years (675, 67%), older than 66 years (33, 3.4%), unknown (6, 0.6%). Reasons for encounter: intentional (768, 76%), adverse drug event/reaction (127, 12.6%), unintentional (66, 6%), and unknown (55, 5.4%). Signs/symptoms: hyperreflexia/clonus/myoclonus (601, 59.5%), agitation (337, 33.4%), tachycardia (256, 25.3%), rigidity (140, 13.9%), seizures (139, 13.7%), and hyperthermia (29, 2.9%). COMPLICATIONS: rhabdomyolysis (97, 9.7%), dysrhythmias (8, 0.8%), and death (1, 0.1%). TREATMENTS: benzodiazepines 67% (677/1010), cyproheptadine 15.1% (153/1010). There were 192 different xenobiotics reported with 2046 total exposures. Antidepressants were most common (915, 44.7%) with bupropion the most frequent overall (147, 7.2%). Common non-antidepressants were dextromethorphan (95, 6.9%), lamotrigine (64, 3.1%), and tramadol (60, 2.9%). DISCUSSION: Serotonin toxicity most often occurred in adult patients with intentional overdose. Antidepressants were the most common agents of toxicity. Interestingly, bupropion, a norepinephrine/dopamine reuptake inhibitor, was the most frequently mentioned xenobiotic. Though often cited as a potential antidote, only 15% of patients received cyproheptadine. Severe toxicity was rare. A single death was reported.
Asunto(s)
Antidepresivos/toxicidad , Sobredosis de Droga/epidemiología , Sistema de Registros/estadística & datos numéricos , Conducta Autodestructiva/epidemiología , Síndrome de la Serotonina/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Sobredosis de Droga/mortalidad , Sobredosis de Droga/fisiopatología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Síndrome de la Serotonina/tratamiento farmacológico , Síndrome de la Serotonina/mortalidad , Síndrome de la Serotonina/fisiopatología , Factores Sexuales , Sociedades Médicas , Toxicología/estadística & datos numéricos , Adulto JovenRESUMEN
Serotonin syndrome is a potentially fatal condition caused by drugs that affect serotonin metabolism or act as serotonin receptor agonists. Monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors are the medications most commonly associated with serotonin syndrome. Serotonin syndrome can be mild and of short duration, but a prolonged course, life-threatening complications, and death are possible. Detection of serotonin syndrome is not difficult if the diagnostic criteria are understood and properly used, but the syndrome has no confirmatory tests and other drug-induced syndromes can, to a degree, mimic serotonin syndrome. The treatment is symptomatic and supportive. Antidotal therapies are available, but the evidence for their effectiveness is limited. If serotonin syndrome is promptly identified and aggressively treated, the patient should fully recover.
Asunto(s)
Causas de Muerte , Inhibidores de la Monoaminooxidasa/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Síndrome de la Serotonina/inducido químicamente , Síndrome de la Serotonina/mortalidad , Enfermedad Crítica , Relación Dosis-Respuesta a Droga , Urgencias Médicas , Femenino , Humanos , Masculino , Inhibidores de la Monoaminooxidasa/administración & dosificación , Medición de Riesgo , Síndrome de la Serotonina/fisiopatología , Síndrome de la Serotonina/terapia , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Análisis de SupervivenciaRESUMEN
OBJECTIVES: To review the diagnosis and management of four selected psychiatric emergencies in the intensive care unit: agitated delirium, neuroleptic malignant syndrome, serotonin syndrome, and psychiatric medication overdose. DATA SOURCES: Review of relevant medical literature. DATA SYNTHESIS: Standardized screening for delirium should be routine. Agitated delirium should be managed with an antipsychotic and, possibly, dexmedetomidine in treatment-refractory cases. Delirium management should also include ensuring a calming environment and adequate pain control, minimizing benzodiazepines and anticholinergics, normalizing the sleep-wake cycle, providing sensory aids as required, and providing early physical and occupational therapy. Neuroleptic malignant syndrome should be treated by discontinuing dopamine blockers, providing supportive therapy, and possibly administering medications (benzodiazepines, dopamine agonists, and/or dantrolene) or electroconvulsive therapy, if indicated. Serotonin syndrome should be treated by discontinuing all serotonergic agents, providing supportive therapy, controlling agitation with benzodiazepines, and possibly administering serotonin2A antagonists. It is often unnecessary to restart psychiatric medications upon which a patient has overdosed in the intensive care unit, though withdrawal syndromes should be prevented, and communication with outpatient prescribers is vital. CONCLUSIONS: Understanding the diagnosis and appropriate management of these four psychiatric emergencies is important to provide safe and effective care in the intensive care unit.
Asunto(s)
Delirio/terapia , Unidades de Cuidados Intensivos , Síndrome Neuroléptico Maligno/terapia , Mal Uso de Medicamentos de Venta con Receta/terapia , Síndrome de la Serotonina/terapia , Enfermedad Crítica/mortalidad , Enfermedad Crítica/terapia , Delirio/diagnóstico , Delirio/mortalidad , Urgencias Médicas , Femenino , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Síndrome Neuroléptico Maligno/diagnóstico , Síndrome Neuroléptico Maligno/mortalidad , Mal Uso de Medicamentos de Venta con Receta/diagnóstico , Medición de Riesgo , Síndrome de la Serotonina/diagnóstico , Síndrome de la Serotonina/mortalidad , Análisis de Supervivencia , Resultado del TratamientoAsunto(s)
Antidepresivos/efectos adversos , Interacciones Farmacológicas , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Síndrome de la Serotonina/inducido químicamente , Síndrome de la Serotonina/epidemiología , Triptaminas/efectos adversos , Antidepresivos/uso terapéutico , Estudios de Casos y Controles , Depresión/tratamiento farmacológico , Femenino , Humanos , Masculino , Trastornos Migrañosos/tratamiento farmacológico , Factores de Riesgo , Síndrome de la Serotonina/mortalidad , Síndrome de la Serotonina/patología , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Triptaminas/uso terapéutico , Estados Unidos , United States Food and Drug AdministrationRESUMEN
In the present study, the effects of amphetamine-class drugs were examined in cases reported to the Victorian coroner from 2001 to 2005 to determine if death can occur from the use of amphetamine-class drugs alone. A total of 169 cases were reviewed where a forensic autopsy detected amphetamine(s) in the blood. Pathology, toxicology, and police reports were analyzed in all cases to ascertain the involvement of amphetamine-class drugs in these deaths. In Victoria, methamphetamine (MA) is the principal abused amphetamine-class followed by methylenedioxymethamphetamine (MDMA). There were six cases in which a cerebral hemorrhage caused death and three cases in which serotonin syndrome was established as being caused by the interaction of MDMA and moclobemide. There were 19 cases in which long-term use of amphetamines was associated with heart disease. There were three cases where amphetamine-class drugs alone were regarded as the cause of death, of which two cases exhibited high levels of MDMA and lesser amounts of MA and/or amphetamine. There were no cases in which significant natural disease was absent and death was regarded as caused by the use of MA. There was no correlation between blood concentration of drug and outcome.
Asunto(s)
Trastornos Relacionados con Anfetaminas/mortalidad , Muerte Súbita/etiología , Adolescente , Adulto , Anfetaminas/sangre , Australia/epidemiología , Enfermedades Cardiovasculares/epidemiología , Causas de Muerte , Interacciones Farmacológicas , Femenino , Patologia Forense , Toxicología Forense , Humanos , Masculino , Persona de Mediana Edad , Síndrome de la Serotonina/mortalidad , Hemorragia Subaracnoidea/mortalidadAsunto(s)
Agranulocitosis/inducido químicamente , Antipsicóticos/efectos adversos , Clozapina/efectos adversos , Síndrome Neuroléptico Maligno/etiología , Psicotrópicos/efectos adversos , Síndrome de la Serotonina/etiología , Agranulocitosis/mortalidad , Agranulocitosis/prevención & control , Dopamina/fisiología , Antagonistas de Dopamina/efectos adversos , Monitoreo de Drogas/métodos , Monitoreo de Drogas/enfermería , Humanos , Síndrome Neuroléptico Maligno/mortalidad , Síndrome Neuroléptico Maligno/prevención & control , Rol de la Enfermera , Educación del Paciente como Asunto , Selección de Paciente , Enfermería Psiquiátrica/métodos , Factores de Riesgo , Serotonina/fisiología , Antagonistas de la Serotonina/efectos adversos , Síndrome de la Serotonina/mortalidad , Síndrome de la Serotonina/prevención & controlRESUMEN
The serotonin (5-HT) syndrome is the most serious side effect of antidepressants, and it often necessitates pharmacotherapy. In the present study, the efficacy of several drugs was evaluated in an animal model of the 5-HT syndrome. When 2 mg/kg of clorgyline, a type-A monoamine oxidase inhibiting antidepressant, and 100 mg/kg of 5-hydroxy-L-tryptophan, a precursor of 5-HT, were administered intraperitoneally to rats to induce the 5-HT syndrome, the rectal temperature of the rats increased to more than 40 degrees C, and all of the animals died by 90 min after the drug administration. The noradrenaline (NA) levels in the anterior hypothalamus, measured by microdialysis, increased to 15.9 times the preadministration level. Pretreatment with propranolol (10 mg/kg), a 5-HT(1A) receptor antagonist as well as a beta-blocker, and dantrolene (20 mg/kg), a peripheral muscle relaxant, did not prevent the death of the animals, even though these two drugs suppressed the increase in rectal temperature to some extent. Chlorpromazine and cyproheptadine prevented the lethality associated with the 5-HT syndrome only at high doses. By contrast, pretreatment with ritanserin (3 mg/kg) and pipamperone (20 mg/kg), both potent 5-HT(2A) receptor antagonists, completely prevented the increase in rectal temperature and death of the animals, and the hypothalamic NA levels in these two groups increased less than that in the other groups. These results suggest that potent 5-HT(2A) receptor antagonists are the most effective drugs for treatment of the 5-HT syndrome, and that NA hyperactivity occurs in the 5-HT syndrome.
Asunto(s)
Fiebre/prevención & control , Receptores de Serotonina/metabolismo , Ritanserina/farmacología , Antagonistas de la Serotonina/farmacología , Síndrome de la Serotonina/prevención & control , 5-Hidroxitriptófano , Animales , Núcleo Hipotalámico Anterior/efectos de los fármacos , Núcleo Hipotalámico Anterior/metabolismo , Antidepresivos , Temperatura Corporal/efectos de los fármacos , Butirofenonas/farmacología , Clorpromazina/farmacología , Clorgilina , Ciproheptadina/farmacología , Dantroleno/farmacología , Modelos Animales de Enfermedad , Antagonistas de Dopamina/farmacología , Fiebre/inducido químicamente , Fiebre/mortalidad , Masculino , Microdiálisis , Relajantes Musculares Centrales/farmacología , Norepinefrina/metabolismo , Propranolol/farmacología , Ratas , Ratas Wistar , Receptor de Serotonina 5-HT2A , Síndrome de la Serotonina/inducido químicamente , Síndrome de la Serotonina/mortalidad , Vasodilatadores/farmacologíaRESUMEN
RATIONALE: The serotonin (5-HT) syndrome is the most serious side effect of antidepressants, and pharmacologic treatment should be offered in severe cases. OBJECTIVE: In the present study, the effects of risperidone, ketanserin, and haloperidol on an animal model of the serotonin (5-HT) syndrome were evaluated. METHODS: Intraperitoneal administration of 100 mg/kg 5-hydroxy-L-tryptophan (5-HTP) (a precursor of 5-HT) and 2 mg/kg clorgyline (a monoamine oxidase type-A inhibiting antidepressant) induced the 5-HT syndrome in rats. The rectal temperature of the rats was measured, and the microdialysis method was used to measure noradrenaline (NA) levels in the anterior hypothalamus. RESULTS: In the group pre-treated with saline, the NA concentration increased to 13 times the pre-administration level, rectal temperature increased to more than 40 degrees C, and all of the animals died 75 min later. In the group pre-treated with risperidone (0.5 mg/kg), the 5-HT syndrome was completely inhibited, and the NA level increased to 6.5 times the pre-administration level. Ketanserin, a selective 5-HT2A antagonist (5 mg/kg) also inhibited the 5-HT syndrome. In contrast, all of the rats in the group pre-treated with haloperidol (0.5 mg/kg) died earlier than in the saline group. CONCLUSIONS: These results suggest that strong 5-HT2A antagonists such as risperidone, but not dopamine D2 antagonists, counteract lethality due to 5-HT syndrome, and that not only does enhancement of 5-HT activity occur in the 5-HT syndrome, but NA activity also increases.
Asunto(s)
Hipotálamo Anterior/efectos de los fármacos , Norepinefrina/metabolismo , Risperidona/farmacología , Antagonistas de la Serotonina/farmacología , Síndrome de la Serotonina/tratamiento farmacológico , 5-Hidroxitriptófano/efectos adversos , Animales , Antidepresivos/efectos adversos , Temperatura Corporal/efectos de los fármacos , Clorgilina/efectos adversos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Hipotálamo Anterior/metabolismo , Masculino , Ratas , Ratas Wistar , Receptor de Serotonina 5-HT2A , Receptores de Serotonina/efectos de los fármacos , Risperidona/uso terapéutico , Antagonistas de la Serotonina/uso terapéutico , Síndrome de la Serotonina/metabolismo , Síndrome de la Serotonina/mortalidadAsunto(s)
Antidepresivos de Segunda Generación/efectos adversos , Paroxetina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Síndrome de la Serotonina/inducido químicamente , Humanos , Paroxetina/envenenamiento , Síndrome de la Serotonina/mortalidad , Inhibidores Selectivos de la Recaptación de Serotonina/envenenamientoRESUMEN
The serotonin syndrome is a rare, but potentially fatal complication to treatment with serotonin reuptake inhibitors. Due to increasing prescription of these drugs the condition must be expected to occur more often. Symptoms include changes in mental status (confusion, agitation and restlessness), neuromuscular symptoms (shivering, ataxia, myoclonus and hyperreflexia) and autonomic dysfunction (fever, diaphoresis, hypertension and tachycardia). The syndrome is most often produced by concurrent use of two or more drugs that enhance serotonin neurotransmission. Monotherapy may also elicit the syndrome. We report the development of serotonin syndrome with a fatal outcome in a patient treated with paroxetin++. Interactions with alimemazin++, melperon++ and karbamazepin may have contributed to the outcome. The serotonin syndrome usually resolves within 24 hours when the suspected drugs are discontinued. However, there may be a dramatic progression of symptoms requiring intensive supportive care to prevent death.