Serotonin syndrome presenting as acute dizziness with supine hypertension and orthostatic hypotension.

Serotonin syndrome (SS) is a drug-induced clinical syndrome characterised by a combination of cognitive, neuromuscular and autonomic dysfunctions. The symptoms may include mild non-specific symptoms such as tremors and diarrhoea to coma and sudden death. Herein, we describe a case of SS in which acute dizziness was associated with supine hypertension and orthostatic hypotension. A man in his mid-30s had a 10-month history of anxiety, depression and chronic tension-type headache. He had been on amitriptyline (25 mg daily) and sertraline (50 mg daily). Increment of sertraline (75 mg daily) and amitriptyline (75 mg daily) and the addition of tramadol led to the development of acute severe dizziness. Physical examinations demonstrate supine hypertension and orthostatic hypotension. He also met the diagnostic criteria of SS. The administration of cyproheptadine provided a complete response to dizziness, supine hypertension, orthostatic hypotension and other clinical features of SS.

Medication-overuse headache overlapping with serotonin syndrome.

Serotonin syndrome (SS) is an iatrogenic, drug-induced clinical syndrome caused by an increase in the intrasynaptic concentration of serotonin. Serotonin plays a significant role in the pathophysiology of migraines. Upregulation of 5-HT2A receptors is found in medication-overuse headache (MOH). Several migraine medications, both preventative and abortive drugs, act on serotonin receptors. We report two patients with chronic migraine who developed MOH. Besides headache, patients had frequent attacks of dizziness, restlessness, irritability, insomnia, excessive sweating, abdominal discomforts and tremors. These symptoms were suggestive of withdrawal headache. However, on physical examinations, we elicited hyperreflexia, hypertonia, clonus, tachycardia, hypertension, mydriasis and hyperactive bowel sound. Both patients also met the criteria for SS. Cyproheptadine was started. All features, including headaches, got better after cyproheptadine administration within 24 hours. In 7 days, there was practically total improvement. Both patients continued to take cyproheptadine as a preventative medicine, and migraine frequency was under control.

Serotonin syndrome from combination hydrocodone and cyclobenzaprine in a patient with cerebral palsy.

Aim: Serotonin syndrome (SS) is a life-threatening syndrome that occurs with the use of serotonergic drugs, most commonly due to two or more agents. Cerebral palsy is associated with mood disorders, and more commonly pain, with a prevalence of up to 50-80%. Case presentation: A 58-year-old female with cerebral palsy, metastatic malignancy and mood disorder who presented to the emergency department with acute-on-chronic pain, and signs of SS. She was initiated on iv. dilaudid, titrated off oral medications and scheduled for a left-sided sacroiliac joint injection. Results: It was suspected that due to additional doses of hydrocodone and cyclobenzaprine, she developed moderate-SS. Conclusion: Physicians need to be cognizant of comorbidities and uncommon pain medications that can predispose patients to SS.

Fatal serotonin syndrome: a systematic review of 56 cases in the literature.

INTRODUCTION: Serotonin syndrome (SS) is a drug-induced potentially life-threatening clinical condition. There is a paucity of data on the risk factors, clinical course, and complications associated with fatal SS. OBJECTIVE: To characterize the epidemiological profile, clinical features, and risk factors associated with fatal SS through a systematic review. METHODS: We performed a systematic review of MEDLINE and Google Scholar for case reports, case series, or cohort studies of fatal SS. RESULTS: Initial database search identified 2326 articles of which 46 (56 patients) were included in the final analysis. The mean age was 42.3 years (range 18-87 years) with female predominance (57%). North America and Europe constitute 80% of the reported fatal SS. The symptoms evolved very rapidly, within 24 h after the administration of serotonergic drugs in 59% of the cases. Fever (61%) was the most common symptom, followed by seizure (36%) and tremors (30%). The mean temperature in the reported cases (25 patients) was 41.6 ± 1.3 °C (range 38.3-43.5 °C). SS was reported to occur with the maintenance dosage of serotonergic agents, after initiation of the drug for the first time, and addition of the drugs for the development of another unrelated illness. Creatine kinase (CK) activities were elevated (>3 times of the upper limit of normal) in eighteen patients, and it was very high (>25,000 IU/L) in four patients. Presence of high grade fever, seizures, and high CK activities may be associated with severe SS. Nine patients (16%) received 5-HT2A antagonists as a therapy. About 50% of patients died within 24 h of the onset of symptoms. CONCLUSIONS: While fatal SS is rare, frequently observed features include hyperthermia, seizures, and high CK activities. Cyproheptadine use appears infrequent for these patients.

Posterior reversible encephalopathy syndrome in a patient with serotonin syndrome.

Serotonin syndrome (SS) is a drug-induced clinical syndrome, characterised by a triad of cognitive impairment, autonomic hyperactivity and neuromuscular abnormalities. Hypertension, one of the common autonomic manifestations in SS, may lead to lead to several life-threatening conditions. Herein, we report a case of SS who had posterior reversible encephalopathy syndrome (PRES) because of high blood pressure.A young male with a 5-month history of chronic tension-type headache and depression had been receiving amitriptyline and paroxetine. Increment of paroxetine led to the development of various new clinical features, fulfilling the Hunter criteria of SS. MRI brain revealed high-signal intensity lesions on T2 fluid-attenuated inversion recovery, and T2-weighted imaging in the posterior regions of the occipital, parietal, temporal and cerebellum lobes, suggestive of PRES. The patient responded to cyproheptadine. Autonomic hyperactivity, due to SS, is the most likely explanation of this association.

HyperCKemia and rhabdomyolysis in the neuroleptic malignant and serotonin syndromes: A literature review.

Neuroleptic malignant syndrome and serotonin syndrome are two syndromes whose molecular bases remain poorly understood. The phenotypes of both syndromes overlap with other syndromes that have a clear genetic background, in particular RYR1-related malignant hyperthermia. Through a literature review, performed according to the PRISMA guidelines, we aimed to report the clinical features of both syndromes, and the results of genetic testing performed. 10 case series and 99 case reports were included, comprising 134 patients. A male predominance of 58% was found. The median age was 35 (range 4-84) years. Eight patients experienced recurrent episodes of rhabdomyolysis. Genetic analysis was performed in eleven patients (8%), revealing four RYR1 variants, three likely benign (p.Asp849Asn, p.Arg4645Gln, p.Arg4645Gln) and one variant of uncertain significance (p.Ala612Thr). This review underlines that a subset of patients with neuroleptic malignant syndrome and serotonin syndrome develop recurrent episodes of rhabdomyolysis. This recurrent pattern suggests a possible underlying (genetic) susceptibility. However, the genetic background of neuroleptic malignant syndrome and serotonin syndrome has only been investigated to a very limited degree so far. The increasing availability of next generation sequencing offers an opportunity to identify potentially associated genetic backgrounds, especially in patients with recurrent episodes or a positive family history.

Underlying Serotonin Syndrome, Masked by Community-Acquired Pneumonia and Myocardial Ischemia.

BACKGROUND Serotonin syndrome is a life-threatening condition that involves overstimulation serotonin receptors, which can be caused by medication overdose, drug-drug interactions, and regular doses of medications. It is often an overlooked diagnosis due to the presenting symptoms. CASE REPORT Our patient was a 79-year-old man with a past medical history significant for coronary artery disease status after coronary bypass surgery who presented to the Emergency Department with altered mental status. Vital signs were significant for hyperthermia. On initial assessment, he was only oriented to person and demonstrated shaking rigors. Lab test results were significant for leukocytosis, with troponins 2.94. A chest X-ray revealed left lower-lobe opacification. He was initially treated for community-acquired pneumonia and his elevated troponin required further work up. He was moved to the Intensive Care Unit (ICU) due to worsening respiratory distress, shaking tremors, and confusion. His troponins remained elevated. On his third day of hospitalization, his rigors had improved, but clonus was present. A medication review revealed the patient was on sertraline. He was started on cyproheptadine. The next morning, his mental status had improved to alert and oriented, and his condition returned to baseline. Upon discharge to a rehab facility, sertraline was discontinued. CONCLUSIONS Serotonin syndrome is a condition that is often not initially recognized. Our patient had multiple health problems and presented with altered mental status and tremors, and serotonin syndrome was not recognized until a full neurological exam and medication review had been done. It is important for physicians to be aware of serotonin syndrome as a differential diagnosis, as the symptoms can be masked by other presenting symptoms.

Multivisceral Failure in a Context of Serotonin Syndrome Induced by MDMA: The Investigation of a Unique and Nationwide Network.

: The occasional ingestion of 3,4-methylenedioxy-N-methylamphetamine (MDMA) presents serious risks of side effects including death through multivisceral failure in a context of serotonin syndrome. The significant increasing evolution of illicit MDMA street dosages over the past 2 decades and the difficulty for physicians to know what quantity the patients may have consumed, make MDMA a drug with unpredictable effects. Through this case report of a 16-year-old Caucasian, we made use of a unique and nationwide French health monitoring system called TREND (Recent Trends and New Drugs)-SINTES (National Identification System for Drugs and Substances), which, combined with the hair follicle test, can assist medical practitioners in rapidly establishing a precise diagnosis and consequently provide the most appropriate treatment for each individual case in a timely manner.

Serotonin Syndrome in Obstetrics: A Case Report and Review of Management.

Serotonin syndrome (SS) is a life-threatening condition, usually precipitated by a combination of serotonergic agents. Data regarding the incidence and management of SS in obstetrics are limited. This study presents a case of SS provoked by an atypical antipsychotic in a second trimester, singleton gestation, and reviews the management of SS in an obstetric patient. We present a case of a schizophreniform, pregnant patient with a singleton gestation admitted to a community, military hospital for serotonin syndrome. The patient was admitted to the intensive care unit (ICU) by the obstetrics team, where she was managed conservatively. The cornerstones of therapy were as follows: discontinuation of offending agent, intravenous fluids, supplemental oxygen, telemetry, and hourly neurological assessments. Fetal status was monitored daily. After stabilization, the patient was transferred from the ICU to inpatient psychiatry for continued care. Although serotonin syndrome is infrequently encountered in obstetrics, it is paramount that all obstetricians are familiar with its recognition and management, particularly in community hospital settings. The low incidence of reported SS is largely attributed to under-recognition, as the syndrome can mimic other more common obstetric diagnoses such as preeclampsia. Given the increasing prevalence of mental health disorders, it is essential for obstetricians to be aware of the potential for SS in our patient population.

Fluoxetine overdose in a teenager resulting in serotonin syndrome, seizure and delayed onset rhabdomyolysis.

A 14-year-old young adult took an overdose of 1.2 g of fluoxetine, a selective serotonin reuptake inhibitor (SSRI) that he had been prescribed for depression. He had a generalised tonic/clonic seizure at 6 hours postingestion.After the seizure, he developed signs consistent with serotonin syndrome: fine tremor, agitation, sweating and hyperreflexia. This was followed by severe muscle pain and rhabdomyolysis with peak creatine kinase (CK) of 33 941 at 74 hours. He was managed with intravenous fluids and analgesia and discharged after 4 days, having avoided renal injury. The use of SSRI's such as fluoxetine in teenagers has increased in recent years. While it is generally considered benign in overdose, this report illustrates the severe consequences of overdose at high quantities and discusses appropriate management in these cases. We note that in this case, there was a delayed onset of rhabdomyolysis with peak CK at 74 hours postingestion.

Case of Serotonin Syndrome Initially Presenting as Diffuse Body Pain.

BACKGROUND Serotonin syndrome is a common yet potentially life-threatening condition caused by increased serotonergic activity, usually from serotonergic pharmaceutical agents. Primary features of serotonin syndrome include mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. However, the presentation of serotonin syndrome is often quite variable, leading to its under-diagnosis. CASE REPORT A 50-year-old female with chronic kidney disease on peritoneal dialysis presented to the Emergency Department with severe, diffuse body pain. Over the course of her hospital stay, she developed severe nausea, vomiting, and diarrhea followed by hyperreflexia and inducible clonus. Laboratory studies were remarkable for elevated liver transaminases. Review of her medications revealed several serotonergic agents, including duloxetine, tramadol, and ondansetron. Given her symptoms and the multiple serotonergic agents she was taking, she was diagnosed with serotonin syndrome. Discontinuation of the serotonergic agents led to resolution of her symptoms over the course of 4 days. CONCLUSIONS Our patient's initial presentation of diffuse body pain highlights the variable presentation of serotonin syndrome. Our case also demonstrates the importance of recognizing serotonin syndrome, as the supportive ondansetron we gave to alleviate her nausea and vomiting likely exacerbated her serotonin syndrome.

Tramadol: Understanding the Risk of Serotonin Syndrome and Seizures.

Tramadol is commonly prescribed for pain control because it presents a lower risk for addiction and respiratory depression compared to other opioids. However, tramadol's serotonin and norepinephrine reuptake inhibitory effects result in a unique adverse effect profile. Two such adverse events are serotonin syndrome and seizures. The prevalence of tramadol-induced serotonin syndrome and seizures is modest in the general population, but if left untreated, the morbidity and mortality can be high; therefore, prompt recognition and management is essential. Various risk factors such as medical comorbidities, use or abuse of supratherapeutic doses of tramadol, and concomitant administration of proconvulsant serotonergic cytochrome P-450 inhibitors will help clinicians identify individuals at an elevated risk for serotonin toxicity and seizures. Serotonin syndrome and seizures can be effectively treated by administering benzodiazepines, providing supportive care, and discontinuing tramadol and other contributing agents. Cyproheptadine should be administered in moderate to severe cases of serotonin syndrome. Our objective is to summarize the literature on the pharmacology, epidemiology, risk factors, clinical presentations, and evidence-based management of tramadol-related seizures and serotonin syndrome.

Vasoplegic Shock Treated with Methylene Blue Complicated by Severe Serotonin Syndrome.

INTRODUCTION: Management of severe vasoplegic shock in overdose can be very challenging. We describe a case of severe refractory vasodilatory shock in poisoning where methylene blue (MB) was used with success. However, the patient subsequently developed severe Serotonin Syndrome (SS) as a result of an interaction between serotonergic drugs and MB. CASE REPORT: A 15-year-old male developed severe vasoplegic shock 1.5 hours after overdosing on several different medications including quetiapine slow release, quetiapine immediate release, desvenlafaxine slow release, venlafaxine, amlodipine, ramipril, fluoxetine, promethazine and lithium. His vasoplegic shock was resistant to high doses of noradrenaline and vasopressin. MB was administered 6.5 hours post ingestion and within 1 hour there was an improvement in his hemodynamic status and reduction of catecholamine requirements. Twelve hours post ingestion, he developed severe Serotonin Syndrome that lasted 5 days as a result of interaction between MB, a reversible monoamine oxidase inhibitor (MAO-I), and the antidepressants taken in overdose. MB had a calculated half-life of 38 hours. CONCLUSION: MB is a useful additional strategy for severe drug induced vasodilatory shock and may be potentially life-saving. Clinicians should be aware that it can interact with other drugs and cause life-threatening Serotonin Syndrome. Lower doses or shorter durations may be wise in patients at risk of this interaction.

[Treatment of hyperthermia].

Hyperthermia is an uncontrolled elevation of body temperature exceeding the body's ability to dissipate heat. Hyperthermia can result in dangerously high core temperatures and can rapidly become fatal. Common causes include heat stroke, malignant hyperthermia, serotonin syndrome, neuroleptic syndrome, a few endocrine emergencies as well as numerous intoxications. Rapid diagnosis and prompt cooling are pivotal, since the condition triggers a cascade of metabolic events which may progress to irreversible injury or death. Ice-water immersion and evaporative cooling are the methods of choice.

Serotonin Syndrome Following Combined Administration of Dopaminergic and Noradrenergic Agents in a Patient With Akinetic Mutism After Frontal Intracerebral Hemorrhage: A Case Report.

BACKGROUND: Serotonin syndrome (SS) is a potentially life-threatening condition that can be caused by use of proserotonergic drugs. Several studies have reported that combined administration of various medications may induce SS. We report a case of SS in a patient who was being treated with dopaminergic and noradrenergic drugs. CASE PRESENTATION: A 55-year-old man with a right frontal intracerebral hemorrhage extending to the left cerebral hemisphere presented with clinical features of akinetic mutism. Three months after onset, dopaminergic (methylphenidate, levodopa/benserazide) and noradrenergic (atomoxetine) drugs were administered to enhance his cognitive function. His cognitive function gradually improved during 8 weeks of dose escalation. One day after the dose of atomoxetine was increased from 40 mg/d to 60 mg/d, the patient developed inducible clonus, rigidity, diarrhea, tachycardia, and hyperthermia, in keeping with a diagnosis of SS. The symptoms and signs suggestive of SS resolved on the day following cessation of all dopaminergic and noradrenergic drugs. CONCLUSIONS: This case demonstrates that medications generally known as dopaminergic or noradrenergic agents could have serotonergic effects via a mechanism that is yet to be fully elucidated. The clinical manifestations of SS can be diverse, ranging from mild to severe and potentially fatal symptoms. When administering a combination of catecholaminergic agents, clinicians should carefully monitor the patient's neurologic status for unexpected adverse reactions.

Rare case of severe serotonin syndrome leading to bilateral compartment syndrome.

The term 'serotonin syndrome' describes a constellation of symptoms caused by serotonergic overstimulation. Its characteristic clinical presentation consists of encephalopathy, neuromuscular signs and autonomic hyperactivity. After removal of the offending agent, the clinical course is usually self-limited but can occasionally lead to severe symptoms. We report the case of a 68-year-old woman who presented emergently with encephalopathy. Home medications included paroxetine and dextroamphetamine/amphetamine. Physical examination revealed tachycardia, tachypnoea, diaphoresis, rigidity, hyperreflexia and clonus. Given the fast onset of symptoms, a diagnosis of serotonin syndrome was made. Laboratory studies showed acute-on-chronic kidney injury and elevated creatine kinase. The patient's mental status quickly returned to baseline with supportive care. Her rhabdomyolysis, however, persisted and led to acute compartment syndrome in her lower extremities. After bilateral leg fasciotomies and treatment of a severe wound infection with intravenous antibiotics, the patient has now recovered with complete resolution of her symptoms.