Síndrome serotoninérgico inducido por ayahuasca: a propósito de un caso

El síndrome serotoninérgico es un conjunto de signos y síntomas generados por hiperactividad serotoninérgica, caracterizado principalmente por alteración del sistema nervioso central. La medicina tradicional, históricamente utiliza herbales con fines curativos y religiosos que podrían tener efectos sobre el sistema serotoninérgico, receptores de dopamina, glutamato y noradrenalina, en este contexto se menciona la ayahuasca o "yagé" como un brebaje con potencial psicoactivo que por lo general se relaciona con síntomas psicóticos. En esta ocasión presentamos un caso clínico de una paciente con síndrome serotoninérgico posterior al consumo por primera vez de ayahuasca en un ritual indígena. Se trata de una paciente femenina de 31 años quien por primera vez ingirió yagé y en cantidad desconocida durante dos días consecutivos en el municipio de Cachipay, Cundinamarca, por sus síntomas clínicos se consideró que cursaba con un síndrome serotoninérgico, recibió tratamiento con adecuado control de su cuadro. Existen múltiples reportes bibliográficos sobre trastornos psicóticos derivados especialmente del uso de DMT en preparación de ayahuasca, sin embargo, la ocurrencia de síntomas psicóticos prolongados, más allá de 48 horas, se considera excepcional; se han descrito en pacientes con antecedentes personales y familiares de psicosis, manía, hipomanía o abuso de sustancias psicoactivas.

Serotonin syndrome is a set of signs and symptoms caused by serotonergic hyperactivity, primarily characterized by alterations in the central nervous system. Historically, traditional medicine has used herbal remedies for healing and religious purposes, which could affect the serotonergic system, dopamine, glutamate, and noradrenaline receptors. In this context, ayahuasca or «yagé» is mentioned as a brew with psychoactive potential that is generally associated with psychotic symptoms. Here, we present a clinical case of a patient with serotonin syndrome following her first-time consumption of ayahuasca in an indigenous ritual. The patient is a 31-year-old female who ingested an unknown quantity of yagé over two consecutive days in Cachipay, Cundinamarca. Given her clinical symptoms, she was considered to have serotonin syndrome and received treatment with adequate control of her condition. Multiple reports in the literature discuss psychotic disorders especially from DMT use in ayahuasca preparation; however, the occurrence of prolonged psychotic symptoms beyond 48 hours is considered exceptional and has been described in patients with personal and family histories of psychosis, mania, hypomania, or abuse of psychoactive substances.

Risk Factors and Clinical Correlates of Pediatric Serotonin Syndrome in Hospitalized Suicide Attempters.

Objective: To evaluate the risk factors and clinical correlates of pediatric serotonin syndrome (SS) given that research on SS in adults exists, there is a dearth of literature on pediatric SS. Study design: We conducted a retrospective chart review of 183 pediatric patients who were medically hospitalized after a suicide attempt. We investigated associations between SS and several of its risk factors and clinical correlates. We also assessed the sensitivity/specificity of Hunter's criteria and criterion symptoms in predicting SS. Results: SS occurred in 21.7% of patients with a serotonergic overdose. Recent marijuana use and overdose on a selective serotonin reuptake inhibitor were significantly associated with SS. Individuals with SS required a greater number of days to be medically stabilized and had a greater likelihood of being placed on a ventilator during treatment. Hunter's criteria had 66.7% sensitivity and 92.3% specificity in diagnosing SS. Conclusions: Our study reveals both novel risk factors associated with SS (eg, recent marijuana use) and clinical correlates for patients with pediatric SS. In children, Hunter's criteria appeared to have good specificity but poor sensitivity in identifying SS. Our results set the stage for future work aimed at enhancing clinicians' ability to more rapidly identify and treat pediatric SS.

Síndrome serotoninérgico como reacción adversa infrecuente ante la sinergia entre Linezolid y Fentanilo: presentación de caso / Serotonin syndrome as an infrequent adverse reaction to synergy between Linezolid and Fentanyl: case presentation

Resumen El síndrome serotoninérgico es una condición potencialmente mortal causada por medicamentos que afectan el metabolismo de la serotonina o que actúan como agonistas directos del receptor de esta o una combinación de ambos. El síndrome da lugar a una variedad de manifestaciones mentales, autonómicas y neuromusculares, que pueden variar desde leves hasta potencialmente mortales. Se reporta el caso clínico de un paciente el cual desarrolló este síndrome por la coadministración y sinergismo de linezolid y fentanilo, con una gran variedad de características clínicas, desde las más sutiles, como cifras tensionales altas de difícil manejo mientras se encontraba bajo el efecto de sedoanalgesia, hasta las manifestaciones más floridas del síndrome posterior a la suspensión de esta. La asociación de estos medicamentos representa una etiología poco informada que puede favorecer la aparición del síndrome, mientras que el uso de benzodiazepinas puede enmascarar el cuadro dificultando su diagnóstico. MÉD.UIS.2020;33(3): 59-66

Abstract Serotonin syndrome is a life-threatening condition caused by medications that affect serotonin metabolism or that act as direct agonists for serotonin receptor or a combination of both. The syndrome gives rise to a variety of mental, autonomic, and neuromuscular manifestations, which can range from mild to life-threatening. We report a clinical case of a patient who developed this syndrome due to the co-administration and synergism of linezolid and fentanyl, with a wide variety of clinical characteristics, from the most subtle, such as high blood pressure levels difficult to manage while under the effect of sedoanalgesia, to the most florid manifestations of the syndrome after 48 hours of its suspension. The association of these drugs represents a poorly reported etiology that may favor the appearance of the syndrome, while the use of benzodiazepines may mask the condition, making its diagnosis difficult. MÉD.UIS.2020;33(3): 59-66

Serotonin syndrome associated with methadone and milk thistle seeds: a case report

Abstract Background Serotonin syndrome is rarely, potentially life threatening condition, associated with use of serotonin acting medications and psychoactive drugs. In the majority of cases the symptoms occur soon after the initiation of a new drug or a change in the dose. Objective To present a case report and to describe the possible mechanism of development of serotonin syndrome during the interactions between milk thistle seeds and methadone on hepatic cytochrome enzyme system P450. Methods A case report of a young man on regular therapy with methadone, who develop a serotonin syndrome after ingestion a high dose of milk thistle seeds. Results Commercial preparations of milk thistle include the extract silibinin, which exhibits no beneficial or harmful drug interactions at normal doses, but at higher concentrations it can lead to dose-dependent effects on methadone metabolism, through inhibition of CYP3A4 and P-glycoprotein. As a result, it may lead to enhanced serotonin re-uptake inhibition and increased serotonin activity. Discussion Milk thistle is widely used and recommended for detoxification, but it may have serious and life threatening interactions with psychotropic drugs and psychoactive substances when used in high doses.

Amphetamine Derivatives as Monoamine Oxidase Inhibitors.

Amphetamine and its derivatives exhibit a wide range of pharmacological activities, including psychostimulant, hallucinogenic, entactogenic, anorectic, or antidepressant effects. The mechanisms of action underlying these effects are usually related to the ability of the different amphetamines to interact with diverse monoamine transporters or receptors. Moreover, many of these compounds are also potent and selective monoamine oxidase inhibitors. In the present work, we review how structural modifications on the aromatic ring, the amino group and/or the aliphatic side chain of the parent scaffold, modulate the enzyme inhibitory properties of hundreds of amphetamine derivatives. Furthermore, we discuss how monoamine oxidase inhibition might influence the pharmacology of these compounds.

Manejo perioperatorio de nuevos fármacos psiquiátricos / Perioperative management of new psychiatric drugs

Psychoactive drugs, including antidepressants and antipsychotics, are currently one of the most commonly used drugs, so we often find patients who consume them during the perioperative period. Historically, they have been associated with multiple and serious adverse effects, such as serotonin syndrome, but nowadays these are infrequent, especially due to the good safety profile of the new drugs most commonly used. Therefore, it is recommended to keep these drugs in the perioperative period, to avoid adverse effects related to their suspension. Among the novel and most used antidepressants are the so-called duals, such as venlafaxine, desvenlafaxine and duloxetine, these are safe and it is recommended to maintain their use. The same is recommended with drugs such as trazodone, bupropion and mirtazapine. Another antidepressant, vortioxetine, has not reported significant adverse effects in the perioperative period, so it is recommended to maintain its use. Agomelatine, derived from melatonin, is considered safe to maintain and could have beneficial effects by reducing preoperative anxiety and eventually reducing the incidence of postoperative delirium in susceptible patients. Antipsychotics are safe in the perioperative period and, in general, it is recommended to maintain their use.

Los fármacos psiquiátricos, entre los que se encuentran los antidepresivos y antipsicóticos, son de los fármacos más utilizados en la actualidad, por lo que con frecuencia nos encontramos con pacientes que los consumen en el perioperatorio. Históricamente se han relacionado con múltiples y graves efectos adversos, como el síndrome serotoninérgico, pero hoy en día estos son infrecuentes, sobre todo por el buen perfil de seguridad que presentan los nuevos fármacos más utilizados. Por lo anterior, es que en general se recomienda mantener estas drogas en el perioperatorio, para evitar efectos adversos relacionados con su suspensión. Entre los antidepresivos más utilizados se encuentran los denominados duales, como venlafaxina, desvenlafaxina y duloxetina, estos son seguros y se recomienda mantener su uso. Lo mismo se recomienda con drogas como trazodona, bupropión y mirtazapina. Otro más novedoso, la vortioxetina, hasta el día de hoy no ha reportado efectos adversos relevantes en el perioperatorio, por lo que se recomienda mantener su uso. La agomelatina, derivada de la melatonina, se considera segura de mantener y podrían tener efectos beneficiosos al reducir la ansiedad preoperatoria y eventualmente reducir la incidencia de delirium postoperatorio en los pacientes susceptibles. Los antipsicóticos son seguros en el perioperatorio y en general se recomienda mantener su uso.

Maternal and developmental toxicity of the hallucinogenic plant-based beverage ayahuasca in rats.

Rats were treated orally with ayahuasca (AYA) on gestation days (GD) 6-20 at doses corresponding to one-(1X) to eight-fold (8X) the average dose taken by a human adult in a religious ritual, and the pregnancy outcome evaluated on GD21. Rats treated with 4X and 8X doses died during the treatment period (44 and 52%), and those that survived showed kidney injury. Rats surviving the 8X dose showed neuronal loss in hippocampal regions and in the raphe nuclei, and those from the 2X dose neuronal loss in CA1. Delayed intrauterine growth, induced embryo deaths and increased occurrence of foetal anomalies were observed at the 8X dose. At non-lethal doses, AYA enhanced embryolethality and the incidence of foetal soft-tissue and skeleton anomalies. This study suggested that AYA is developmentally toxic and that its daily use by pregnant women may pose risks for the conceptus.

Un diagnóstico no pensado: toxicidad serotoninérgica secundaria a interacción medicamentosa. Caso clínico / An unintended diagnosis: Serotonergic toxicity secondary to drug interactions. Case reports

La toxicidad serotoninérgica es un trastorno con potencial riesgo de vida asociado con un incremento de la actividad serotoninérgica en el sistema nervioso central. Se observa con el uso terapéutico o sobredosis intencional de medicamentos e interacciones inadvertidas (inhibidores selectivos de la recaptación de serotonina-isoniacida). Aunque esta patología está incrementándose, todavía no es bien reconocida por los médicos y sus manifestaciones pueden ser erróneamente atribuidas a otras causas. El objetivo de este artículo es presentar un caso clínico, colaborar con el diagnóstico y mejorar el cuidado de estos pacientes.

Serotonin toxicity is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, intentional self-poisoning and inadvertent interactions (SSRI-isoniazid). Although this pathology is increasingly common, it is not well recognized by physicians and manifestations may be wrongly attributed to another cause. The aim of this paper is to describe the clinical picture of a patient, to collaborate on diagnosis and to improve medical care of these patients.

[An unintended diagnosis: Serotonergic toxicity secondary to drug interactions. Case reports]. / Un diagnóstico no pensado: toxicidad serotoninérgica secundaria a interacción medicamentosa. Caso clínico.

Serotonin toxicity is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, intentional self-poisoning and inadvertent interactions (SSRI-isoniazid). Although this pathology is increasingly common, it is not well recognized by physicians and manifestations may be wrongly attributed to another cause. The aim of this paper is to describe the clinical picture of a patient, to collaborate on diagnosis and to improve medical care of these patients.

La toxicidad serotoninérgica es un trastorno con potencial riesgo de vida asociado con un incremento de la actividad serotoninérgica en el sistema nervioso central. Se observa con el uso terapéutico o sobredosis intencional de medicamentos e interacciones inadvertidas (inhibidores selectivos de la recaptación de serotonina-isoniacida). Aunque esta patología está incrementándose, todavía no es bien reconocida por los médicos y sus manifestaciones pueden ser erróneamente atribuidas a otras causas. El objetivo de este artículo es presentar un caso clínico, colaborar con el diagnóstico y mejorar el cuidado de estos pacientes.

Síndrome serotoninérgico / Serotonin syndrome

Introducción: el síndrome serotoninérgico es una rara afección, con reacción adversa a la administración de determinado grupo farmacológico. Objetivo: demostrar la evolución clínico-anestesiológica de un paciente con síndrome serotoninérgico. Caso clínico: paciente de 37 años con antecedentes de epilepsia, tratado con valproato de sodio. Ingresó al hospital por quemaduras de segundo y tercer grado en ambos miembros inferiores para debridamiento e implante de piel. Lleva tratamiento con tramadol 50 mg/6 h, ácido fólico 5 mg/d, fluoxetina 20 mg/d, tiamina 100 mg/d y vitamina C 500 mg/d. Se administró anestesia general con máscara laríngea. Inducción con fentanilo 100 µg, ketamina 20 mg, propofol 150 mg. Se colocó máscara laríngea 4. Respiración espontánea en modalidad PSVPro con O2 + aire + sevoflurane (CAM 0,6 por ciento). Cuando comenzó la asepsia quirúrgica se evidenció clonus en ambos miembros inferiores. No cambios hemodinámicos, ni de la temperatura (36,1 °C). Gasometría: alcalosis metabólica. Ionograma normal. Se administró 5 mg de midazolam. En el posoperatorio se retiró la máscara laríngea. TA: 106/60. Pulso: 95 lat/min. Temperatura: 35,8 °C, Sat Hb: 98 por ciento. Se constató clonus sostenido inducible al estímulo mínimo bilateral, clonus orbital e hiperreflexia. Se mantuvo en la sala de recuperación por dos horas. Se dio alta para la sala de cuidados especiales con indicaciones. Conclusiones: la evolución fue satisfactoria. Ante un paciente que llega de urgencia, se recomienda evaluar las enfermedades coexistentes y su tratamiento; no hacerlo puede traer consecuencias fatales(AU)

Introduction: The serotonin syndrome is a rare condition and includes an adverse reaction to the administration of a certain pharmacological group. Objective: To show the clinical-anesthesiological evolution of a patient with serotonin syndrome. Clinical case: A 37-year-old patient with a history of epilepsy, treated with sodium valproate. The patient was admitted to the hospital for second and third degree burns on both lower limbs for debridement and skin implant. The patient was treated with tramadol (50 mg every 6 hours), folic acid (5 mg every d), fluoxetine (20 mg every day), thiamin (100 mg every day), and vitamin C (500 mg every day). General anesthesia with laryngeal mask was administered. Induction with fentanyl (100 µg), ketamine (20 mg), propofol (150 mg). Laryngeal mask number 4 was placed. Spontaneous respiration in PSVPro modality with O2, air and sevoflurane (CAM 0.6 percent). When the surgical asepsis began, clonus was evident in both lower limbs. No hemodynamic or temperature changes (36.1 °C). Gasometry: metabolic alkalosis. Normal Ionogram. 5 mg of midazolam were administered. In the postoperative period, the laryngeal mask was removed. TA: 106/60. Pulse: 95 beats/min. Temperature: 35.8 °C, sat Hb: 98 percent. Sustained clonus inducible to minimal bilateral stimulus, orbital clonus and hyperreflexia was found. The patient remained in the recovery room for two hours and was released for the special care room with instructions. Conclusions: The evolution was satisfactory. When a patient arrives urgently, it is recommended to assess the coexisting diseases and their treatment; not doing so can bring fatal consequences(AU)

Síndrome serotoninérgico en anciano con falla renal crónica tratada con linezolid: reporte de caso / Serotonin syndrome in an old man with chronic kidney disease treated with linezolid: Case report

El síndrome serotoninérgico es una reacción adversa y potencialmente mortal a medicamentos; está caracterizado por cambios en el estado mental, hiperactividad autonómica y anormalidades músculo-esqueléticas causadas por exceso de serotonina a nivel central. Se reporta el caso de un paciente de 71 años con enfermedad renal crónica estadio V y cuadro clínico de infección intraabdominal asociada al catéter. Luego de 33 días de la hospitalización presentó temblor en manos, hiperreflexia y taquicardia. Al día 36 se tornó confuso, desorientado e incoherente, con palpitaciones y disneico. Entre los factores de riesgo para desarrollo de síndrome serotoninérgico se encuentra el uso de linezolid, que en combinación de otros medicamentos con acción serotoninérgica -como los inhibidores selectivos de recaptación de serotonina, el litio, la trazodona, entre otros- se asocia con la presentación de este cuadro. El síndrome serotoninérgico puede ser evitado con una buena educación al personal médico y la modificación de las conductas de prescripción de medicamentos; el pilar del tratamiento se basa en la suspensión de los fármacos que están causando el cuadro y el planteamiento de medidas de soporte.

Serotonin syndrome is a potentially fatal adverse reaction to medication. It is described as a clinical entity characterized by changes in mental status, autonomic hyperactivity and musculoskeletal abnormalities caused by excess of serotonin at the central nervous system. A 71 years old patient with history of stage V of chronic kidney disease with clinical symptoms of intraabdominal infection associated with catheter is reported. After 33 days of hospitalization the patient began to show hand tremor, tachycardia and hyperreflexia. On day 36, the patient became confused, disoriented and incoherent, dyspneic and with palpitations. Linezolid in combination with others drugs with serotoninergic action -such as selective serotonin reuptake inhibitors, litium, trazodone and others- has been associated with serotonin syndrome presentation. Serotonin syndrome can be avoided through a combination of medical staff education and the modification of prescription drugs behavior. The mainstay of treatment is based on the suspension of drugs that cause the symptoms and the proposal of support measures.

Jaw stiffness and dental extractions due to pharmacodynamic interaction between mirtazapine and chlorpromazine / Bruxismo y extracciones dentales debido a la interacción farmacodinámica entre mirtazapina y la clorpromazina

A comprehensive assessment of the patient's drug related needs allows identifying health problems drug-induced. It has been demonstrated that each dollar spent on clinical pharmacy services reduces the pooled median cost of health by 4.81 dollars. Jaw stiffness (bruxism) can be a serotonergic manifestation related to drugs with serotonin reuptake inhibition activity. Clinical manifestations also include: agitation, tachycardia, high blood pressure, tremor, fever, dyspnea, diarrhea, mental confusion and insomnia

Síndrome serotoninérgico / Serotonin syndrome

El síndrome serotoninérgico (SS) se caracteriza por la presencia de disfunción autonómica, deterioro neuromuscular y alteraciones en el estado mental. El diagnóstico es clínico y por laboratorio. El tratamiento es mediante medidas de apoyo a base de líquidos, hipotermia, benzodiacepinas y, cuando lo amerite, intubación y ventilación mecánica. El pilar de la intervención farmacológica es ciproheptadina, un antagonista central H1, con un antagonismo periférico 5-HT2A. El medicamento disponible sólo se puede administrar por vía oral, por lo que en enfermos críticos debe administrarse a través de sonda nasoyeyunal. El objetivo de este trabajo es presentar un caso de SS y revisar la literatura al respecto.

The serotonin syndrome (SS) is characterized by a spectrum of signs characterized by autonomic dysfunction, neuromuscular impairment, and alterations in mental status. The diagnosis of the serotonin syndrome is clinical and by laboratory evaluation. Treatment is with active cooling and benzodiazepines to control agitation, and intubation, especially in patients with severe hyperthermia and delirium. The mainstay of pharmacologic intervention is cyproheptadine, a centrally acting H1-antagonist, with a prominent peripheral 5-HT2A antagonism. The drug is only available orally, and if the patient is unable to swallow, the drug should be administered nasogastrically. The objective of this paper is report a case of Serotonin Syndrome and review the literature related to this disease.

Sintomas patogenéticos de serotonina: relato de um grupo de auto-experimentadores / Proving symptoms of serotonin: report of a group of self-experimenters

O valor da auto-experimentação realizada pelo homeopata é inestimável, segundo Hahnemann, seja para o auto-conhecimento, para seu o aprendizado como observador e, principalmente, para a vivência dos princípios homeopáticos. Assim, formou-se, em 2005, em Londrina um grupo de auto-experimentação, composto por vários profissionais homeopatas. Vinte auto-experimentadores (12 no primeiro grupo, em 2005, e 8 no segundo grupo, em 2008) provaram sulfato de serotonina na preparação homeopática 30cH e, posteriormente, os sintomas observados pelos dois grupos foram comparados com aqueles descritos na literatura para a síndrome serotoninérgica (SS). O medicamento Serotonina 30cH despertou 370 sintomas, expressos pelos 20 auto-experimentadores, sendo que os sintomas foram reunidos em 47 grupos. Desses sintomas, muitos apareceram nos dois grupos, compostos por experimentadores diferentes, em momentos diversos. O resultado da comparação entre os sintomas da SS e aqueles surgidos nas auto-experimentações mostrou que dos 32 sintomas da SS relatados pela literatura consultada, 17 deles ocorreram nas auto-experimentações. A auto-experimentação foi uma oportunidade ímpar para a vivência dos princípios homeopáticos e um excelente exercício de auto-observação. A riqueza dos sintomas experimentados aliada à reprodução dos mesmos na segunda experimentação e à coincidência com vários sintomas da SS tornam a serotonina agitada e diluída um medicamento homeopático para ser utilizado na clínica.

The value of the self-experimentation the homeopathic physician carries out on him/herself is priceless, according to Hahnemann, be it to acquire self-knowledge, to learn how to observe or chiefly, to experience the homeopathic principles. Consequently, it was formed in 2005 in Londrina a group of self-experimentation, composed by several homeopathic professionals. Twenty self-experimenters (12 in the first group, in 2005, and 8 in the second group, in 2008) tested serotonin sulfate in homeopathic high dilution 30cH; later on, the symptoms observed by both groups were compared with the ones described in the literature in serotonin syndrome (SS). Homeopathic medicine Serotonin 30cH awakened 370 symptoms among 20 experimenters, which were grouped in 47 classes. From these symptoms, many appeared in volunteers from both groups, which were composed by different volunteers in differen moments. The result of the comparison between the symptoms of SS and the ones reported in the self-experimentations showed that, from de 32 symptoms of SS reported by the literature, 17 also happened in our study. This self-experimentation was an unique opportunity to experience the homeopathic principles...

Síndrome serotoninérgico / Serotonin syndrome

El síndrome serotoninérgico (SS) es una condición clínica asociada al uso de medicamentos agonistas de la serotonina, prescritos para el manejo de enfermedades psiquiátricas y no psiquiátricas como trastornos afectivos, de ansiedad, por dolor, etcétera. Se presenta por una excesiva estimulación de los receptores centrales y perifé-ricos de serotonina produciendo cambios mentales, autonómicos y neuromusculares. Usualmente se resuelve en las primeras 24 horas de iniciados los síntomas con tan solo la suspensión de los medica-mentos y medidas de soporte, sin embargo puede progresar a falla multisistémica y a la muerte de los pacientes. El presente artículo es una revisión teórica de los aspectos fundamentales del SS, iniciando con una breve revisión del sistema de serotonina en cuanto a su anatomía y fisiología para luego revisar los aspectos históricos, de diagnóstico, clínicos y de tratamiento más relevantes.[Muñoz H, Vargas A. Síndrome serotoninérgico. MedUNAB 2004; 7:144-50]

Serotonin syndrome. The serotonin syndrome is a clinical condi-tion associated with serotonin agonists, prescribed to treat some psychiatric and non psychiatric diseases like affective, anxiety and pain disorders. Is due to an excessive stimulation of central and peripheral serotonin receptors that leads to mental, autonomic and neuromuscular changes. Usually the disorder resolves within the first 24 hours after the medications are discontinued, however some patients progress to a multiple organ failure and die. This paper is a theoretical review of the fundamental aspects of the serotonin syndrome, beginning with a brief review of the anatomic and phy-siologic features of serotonin system, to continue to examine the most relevant historic, diagnosis, clinical and treatment aspects of the syndrome