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

Severe complications of tramadol overdose in Iran / 한국역학회지

OBJECTIVES: Severe complications of tramadol overdose have been reported; however, few large-scale studies have investigated this issue. Therefore, this study aimed to explore the presentation and complications of tramadol overdose in patients admitted to an intoxication referral center in northwestern Iran. METHODS: Patients with tramadol overdose admitted to Sina Teaching Hospital in Tabriz, Iran during 2013-2017 were included. For each patient, the following data were collected: demographics, previous drug or medication overdose, whether the patient was in the process of quitting drug use, ingested dose of tramadol and co-ingestants, Glasgow Coma Scale (GCS) score, clinical symptoms at the time of admission, and admission characteristics. Serotonin toxicity was diagnosed in patients who fit the Hunter criteria. Multiple logistic regression was performed to identify variables associated with the incidence of severe complications of tramadol overdose. RESULTS: In total, 512 cases of tramadol overdose were evaluated, of which 359 patients were included, with a median age of 41 years (range, 16-69) and a median tramadol dose of 1,500 mg (range, 500-4,000). The most frequent complications associated with tramadol overdose were hypertension (38.4%), tachycardia (24.8%), and seizure (14.5%). No serotonin toxicity was detected in patients. Having a GCS score 1,000 mg, being in the process of quitting drug use, being 30-49 years old, and male sex were significantly related to the incidence of severe complications of tramadol overdose. CONCLUSIONS: Although seizure was prevalent among Iranian patients with tramadol poisoning, serotonin toxicity and cardiogenic shock were rare findings.

Severe complications of tramadol overdose in Iran / 한국역학회지

OBJECTIVES: Severe complications of tramadol overdose have been reported; however, few large-scale studies have investigated this issue. Therefore, this study aimed to explore the presentation and complications of tramadol overdose in patients admitted to an intoxication referral center in northwestern Iran.METHODS: Patients with tramadol overdose admitted to Sina Teaching Hospital in Tabriz, Iran during 2013-2017 were included. For each patient, the following data were collected: demographics, previous drug or medication overdose, whether the patient was in the process of quitting drug use, ingested dose of tramadol and co-ingestants, Glasgow Coma Scale (GCS) score, clinical symptoms at the time of admission, and admission characteristics. Serotonin toxicity was diagnosed in patients who fit the Hunter criteria. Multiple logistic regression was performed to identify variables associated with the incidence of severe complications of tramadol overdose.RESULTS: In total, 512 cases of tramadol overdose were evaluated, of which 359 patients were included, with a median age of 41 years (range, 16-69) and a median tramadol dose of 1,500 mg (range, 500-4,000). The most frequent complications associated with tramadol overdose were hypertension (38.4%), tachycardia (24.8%), and seizure (14.5%). No serotonin toxicity was detected in patients. Having a GCS score <15, having taken a tramadol dose of >1,000 mg, being in the process of quitting drug use, being 30-49 years old, and male sex were significantly related to the incidence of severe complications of tramadol overdose.CONCLUSIONS: Although seizure was prevalent among Iranian patients with tramadol poisoning, serotonin toxicity and cardiogenic shock were rare findings.

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.

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.

Famotidine-induced reversal of meperidine-related serotonin syndrome: a case report / 대한마취과학회지

Serotonin syndrome is an unexpected fatal adverse event related to serotonergic medication. This case report is the first report describing the possible treatment effect of famotidine on serotonin syndrome. Furthermore, this is the first case report of serotonin syndrome induced by meperidine alone in a patient with no previous history suggesting a susceptibility to serotonin syndrome. A 70-year-old male with no recent history of serotonergic drug use presented with severe serotonin syndrome following ureteroscopy, possibly due to postoperative meperidine administration. The patient's symptoms included hypertension, tachycardia, tachypnea, hyperthermia, myoclonus, diaphoresis, retching, nausea, agitation, and semicoma mentality with no pupillary light reflex. Symptoms began to subside immediately after the administration of intravenous famotidine for prevention of aspiration pneumonia, with mental and neurological symptoms showing improvement initially, followed by autonomic symptoms. This case report suggests that the histamine type 2 receptor antagonist famotidine may be an effective emergency treatment for serotonin syndrome.

Famotidine-induced reversal of meperidine-related serotonin syndrome: a case report / 대한마취과학회지

Serotonin syndrome is an unexpected fatal adverse event related to serotonergic medication. This case report is the first report describing the possible treatment effect of famotidine on serotonin syndrome. Furthermore, this is the first case report of serotonin syndrome induced by meperidine alone in a patient with no previous history suggesting a susceptibility to serotonin syndrome. A 70-year-old male with no recent history of serotonergic drug use presented with severe serotonin syndrome following ureteroscopy, possibly due to postoperative meperidine administration. The patient's symptoms included hypertension, tachycardia, tachypnea, hyperthermia, myoclonus, diaphoresis, retching, nausea, agitation, and semicoma mentality with no pupillary light reflex. Symptoms began to subside immediately after the administration of intravenous famotidine for prevention of aspiration pneumonia, with mental and neurological symptoms showing improvement initially, followed by autonomic symptoms. This case report suggests that the histamine type 2 receptor antagonist famotidine may be an effective emergency treatment for serotonin syndrome.

Codeine Precipitating Serotonin Syndrome in a Patient in Therapy with Antidepressant and Triptan

The serotonin syndrome is a serioius medical condition due due to an intensive stimulation of setonin receptors. It is a rare, but severe, consequence of interaction between serotomimetic agents. This is a report of a 70-year-old woman steadily in therapy with venlafaxine and rizatriptan for migraine and major depressive syndrome. She was admitted to neurology unit for decreased light reflex with miotic pupils, global hyperreflexia, tremor, anxiety, ataxia and incoordination. The patient was diagnosed as a probable case of serotonin syndrome due to a pharmacological interaction between venlafaxine and rizatriptan trigged by opioid intake. In this paper, the development of syntomatology, the clinical examination and the possible pharmacokinetics explanation were carefully discussed and analysed.

Serotonin Syndrome after Clomipramine Overdose in a Child

Serotonin syndrome (SS) is a potentially life-threatening condition associated with increased serotonergic activity in central nervous system and may occur during the use of serotonergic drugs. Although increasing frequency of serotonergic drug use in children, pediatricians, emergency medicine and pediatric intensive care specialists have not enough knowledge and experience about SS that is a potentially life-threatening condition. A 12-year-old girl patient was admitted to our emergency room with the history of involuntary contractions on her extremities and alteration of consciousness. Her physical examination showed agitation, hyperthermia, dilated pupils, tremor, increased deep tendon reflexes, positive spontaneous clonus, agitation, flushed skin and diaphoresis, excessive perspiration, and continuous horizontal ocular movements. The patient diagnosed as SS by clinical history, physical and laboratory findings. In this paper, we will discuss SS occurred in a 12-year-old girl after concurrent clomipramine and risperidone use.

Serotonin Syndrome following Duloxetine Administration in a Fibromyalgia Patient: Case Report and Literature Review

Serotonin syndrome, an adverse drug reaction, is a consequence of excess serotonergic agonism of central nervous system receptors and peripheral serotonergic receptors. Serotonin syndrome has been associated with large numbers of drugs and drug combinations, and serotonin-norepinephrine reuptake inhibitor-induced serotonin syndrome is rare. It is often described as a sign of excess serotonin ranging from tremor in mild cases to delirium, neuromuscular rigidity, and hyperthermia in life-threatening cases. Diagnosis is based on the symptoms and patient's history, and several diagnostic criteria have been developed. We experienced a rare case of fibromyalgia accompanied by tremor, hyperreflexia, spontaneous clonus, muscle rigidity, and diaphoresis after 10 days of single use of duloxetine 30 mg. Only one case of serotonin syndrome resulting from administration of duloxetine has been reported in Korea, however that case resulted from co-administration of fluoxetine. We report here on this case along with a review of the relevant literature.

A case of postoperative serotonin syndrome following the administration of fentanyl, palonosetron, and meperidine: A case report

Serotonin syndrome is an unexpected adverse reaction of serotonergic medication. Some drugs used by anesthesiologists may cause serotonin syndrome. Serotonin syndrome is known to be related to 5-hydroxytryptamine 1A and 5-hydroxytryptamine 2A agonism. However, recent research has revealed evidence that 5-hydroxytryptamine 3 (5-HT3) antagonism can also play a role in serotonin syndrome. Among the 5-HT3 antagonists, palonosetron is the most highly specific. In this study, we present the first case of fentanyl- and meperidine-induced serotonin syndrome precipitated by palonosetron in general anesthesia.

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

Probable tramadol-induced atypical serotonin syndrome in a patient receiving selective serotonin reuptake inhibitor and stopped at 10 days before surgery: A case report

Tramadol can increase the serum level of serotonin, causing serotonin syndrome, which is a potentially life-threatening condition. Serotonin syndrome occurs when tramadol is used in combination with other drugs that affect serotonin. A patient who had been taking selective serotonin reuptake inhibitor and stopped at 10 days before surgery experienced intermittent heart rate elevation, tremor of the upper extremities and mental change after receiving an infusion of tramadol for postoperative pain control. Although he did not show the typical triad of serotonin syndrome (systemic autonomic dysfunction, neuromuscular impairment and mental status change), the patient was suspected to have serotonin syndrome caused by tramadol.

Serotonin syndrome associated with linezolid

Serotonin syndrome (SS) is a potentially life-threatening drug reaction characterized by mental status change, increased neuromuscular tone, and autonomic instability. Linezolid, an oxazolidinone antibacterial agent, is widely used in general hospitals; however, it interacts with some serotonin agonists and may cause SS. We report a case of SS caused by linezolid, without the concomitant use of serotonin agonist. A 72-year-old patient was admitted due to recurrent wound infection of his left ankle. He developed fever, skin rash, and renal function deterioration, and blood eosinophils and liver enzymes increased after administration of vancomycin. The antibiotic was changed to linezolid against methicillin-resistant Staphylococcus aureus. Four days later, he developed agitation, fever, increased blood pressure, and tachycardia. There were no abnormal findings in laboratory and image tests, including brain and chest computed tomography suggesting the cause of his symptoms. He had not taken any serotonin agonists, including serotonin uptake inhibitors and monoamineoxidase-inhibiting antidepressants. When administration of linezolid was stopped, his symptoms improved within 24 hours and fully recovered within 2 days without additional treatments.

Agomelatine: The Novel Antidepressant / 대한정신약물학회지

Major depression is a common mental illness, associated with high morbidity and mortality. Antidepressants have been the first-line therapies due to their confirmed efficacy, however, considering high rate of poor treatment response to these therapies, distressing side effects, and delayed onset of their efficacy, there has been much effort to find alternative treatments for major depression. Recently, evidence regarding disturbed circadian rhythms involved in the pathophysiology of major depression has emerged, the interest on this area has been increasing. Agomelatine is an emerging antidepressant, with a unique profile of selective antagonist at serotonin 2C (5-HT2C) receptors and melatonin receptor agonist. Previous studies have shown its superior efficacy over placebo in treating major depression. Previous trials have shown comparable antidepressant efficacy of agomelatine compared to other standard antidepressants including venlafaxine, sertraline, and fluoxetine. Regarding safety profile of agomelatine, it seems to be not associated with sexual dysfunction and it has less potential for serotonin syndrome or discontinuation syndrome than standard antidepressants including selective serotonin reuptake inhibitors. Considering favorable results on the efficacy and safety of agomelatine in treating depression, it could be a good, safe treatment alternative in the treatment of depression.

Serotonin Syndrome After an Overdose of Dextromethorphan and Chlorpeniramine: Two Case Reports

Dextromethorphan and chlorpeniramine are common ingredients of over-the-counter (OTC) cough pills. They are known to be safe when used alone, however, combination with other serotonergic drugs or use of an overdose can cause serotonergic toxicity. We report on a 43-year-old male and a 57-year-old female who ingested an overdose of antitussive drugs containing dextromethorphan and chlorpeniramine. They commonly presented with altered mentality and hyperreflexia on both upper and lower extremities. After conservative therapies, they were discharged with alert mentality. These cases are meaningful in that there are few cases of serotonin syndrome with an overdose of a combination of dextromethorphan and chlorpeniramine. Careful use with medication counseling for OTC cough pills is needed in order to prevent overdose of these ingredients.

A Case of Serotonin Syndrome Induced by Fluoxetine and Duloxetine Independently in a Same Patient / 대한정신약물학회지

Here we report a case of serotonin syndrome caused by fluoxetine 20 mg and duloxetine 60 mg independently eight week apart. A 65-year old man developed fever, agitation and change of mental status after two weeks treatment with 20 mg of fluoxetine for depressive disorder. He was diagnosed unknown fever origin and discharged when fever subsided as antidepressant stopped. Eight weeks later he was prescribed 60 mg of duloxetine for the treatment of depressed mood. After 18 days on duloxetine he developed fever, agitation, myoclonus and change in mental status again. He improved rapidly after discontinuation of offending drug with supportive care. Despite serotonin syndrome is usually caused by poly-pharmacy of serotonergic drugs, this case shows unusual serotonin syndrome developed by therapeutic dose of two drugs of different classes independently.

A Case of Serotonin Syndrome Due to Amantadine and Escitalopram in End-Stage Renal Disease / 대한내과학회지

Serotonin syndrome is a potentially life-threatening adverse drug reaction caused by excessive serotonergic activity in the nervous system. It is characterized by a triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. Escitalopram is a selective serotonin reuptake inhibitor. Amantadine, an anti-influenza agent, is commonly used for the treatment of parkinsonism; it also has serotonergic activity. Amantadine can induce toxicity in patients with renal dysfunction because it is excreted mainly in the urine. We report a rare case of serotonin syndrome in a 73-year-old woman with Parkinson's disease, depression, and end-stage renal disease undergoing maintenance hemodialysis. She presented with confusion, myoclonus, and fever after starting escitalopram for her depression while on amantadine for parkinsonism. Based on this case, amantadine as well as escitalopram should be placed on the list of medications that can precipitate serotonin syndrome. The side effects of these drugs should be monitored, especially in end-stage renal disease.

Síndrome serotonínico pediátrico: reporte de un caso / Serotonin syndrome pediatric: case report

El síndrome serotonínico es un cuadro neurológico agudo debido a hiperactividad serotoninérgica, por la interacción de drogas que refuerzan o mimetizan la acción del neurotrasmisor. La incidencia del síndrome de serotonina es ascendente por la disponibilidad creciente de fármacos serotoninérgicos como los antidepresivos. Por ello es importante que los médicos reconozcan y manejen adecuadamente el síndrome serotonínico. Este reporte de caso se refiere a una intoxicación accidental por el neuroléptico atípico olanzapina en un niño de 2 años, quien desarrolló manifestaciones clínicas como agitación, sudoración, mioclonías, clonus espontáneo e hipertermia, considerados como criterios diagnóstico del cuadro. La terapia consistió en descontaminación interna con lavado gástrico, carbón activado y sulfato de sodio, ciproheptadina, propranolol y furosemida. Su evolución fue satisfactoria. En nuestro país hay disponibilidad de la mayoría de los fármacos causales y tienen amplio uso, por lo que es probable el subregistro del síndrome. De allí la importancia de este reporte de caso

Serotonin syndrome is an acute neurologic picture due to serotonergic hyperactivity, due to the interaction of drugs that enhance or mimic the action of the serotonin. The incidence of serotonin syndrome is rising because of the growing availability of serotonergic drugs such as antidepressants. It is therefore important that clinicians recognize and manage appropriately this syndrome. This case report refers to an accidental poisoning by the atypical neuroleptic olanzapine in a 2 year old boy who developed clinical manifestations such as agitation, sweating, myoclonus, spontaneous clonus and hyperthermia, considered as diagnostic criteria for the syndrome. Therapy consisted of internal decontamination with gastric lavage, activated charcoal and sodium sulfate, cyproheptadine, propranolol and furosemide. The clinical outcome was satisfactory. In our country the majority of the causal drugs are easily available and widely employed, for which reason it is probable that this syndrome is under registered. Hence the importance of this case report

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...