Diagnosis Of Serotonin Syndrome Research Articles

Is the combination of domperidone and metoclopramide increasing the risk of developing serotonin syndrome?: a case report

Metoclopramide and domperidone are dopamine antagonists that can cause an acute dystonic reaction. Metoclopramide is a rare but major contributor to serotonin syndrome, particularly when used with other serotonergic agents. Serotonin syndrome is a rare, potentially life-threatening adverse reaction characterized by a triad of altered mental status, autonomic dysfunction, and neuromuscular hyperactivity that typically results from exposure to serotonergic agents. Herein, we report a previously healthy 9-year-old girl who was brought to the emergency department with an alteration in the level of conscious and involuntary repetitive movements after approximately 24 hours of receiving a therapeutic dose of metoclopramide and domperidone. Physical examination showed tachycardia, hyperthermia, and a Glasgow Coma Scale score of 11, as well as mydriasis and hyperreflexia. In addition to resolving the symptoms after administering midazolam and diphenhydramine, the diagnosis of serotonin syndrome was made based on the classical symptoms and signs, which met the Hunter criteria. This case indicates the need for clinical awareness of the life-threatening syndrome and caution with medications having potential interactions with metoclopramide.

Serotonin syndrome: An often-neglected medical emergency.

Optimum serotonin level in the serotonergic synapses of the central nervous system (CNS) is related to mood, behavior, and sleep. Serotonin syndrome (SS) is a rare yet very dangerous adverse effect resulting from increased serotonin in CNS. The diagnosis of SS is based on the presence of clinical symptoms, which can include agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, tremors, sweating, and diarrhea. SS is invariably caused by inadvertent use of serotonergic medicines. There is an ever-growing list of medicines that are associated with the risk of SS. Some of the common classes of drugs that can contribute to the development of SS include selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants, stimulants (e.g., amphetamines and cocaine), lithium, opioids, drugs used for recreational purposes like ecstasy Methylenedioxymethamphetamine (MDMA), and some herbal supplements (e.g., St. John's Wort). SS can occur when these medications are taken alone or in combination, especially when a new medication is added, or the dose of an existing medication is changed. The management of SS typically involves discontinuing the use of the substance that caused the excess serotonin levels and providing supportive care, such as intravenous fluids and electrolytes. In severe cases, benzodiazepines may be used to control agitation and muscle rigidity, while serotonin antagonists, such as cyproheptadine, may be used to reduce serotonin levels. The literature review points to a general unawareness among physicians about the condition or drugs associated with it. Consequently, this potentially fatal condition is overlooked. There is a need for regular information updates and reminders to all those who prescribe medications to the patients.

The use of diagnostic criteria to diagnose and treat serotonin syndrome

This paper aims to explore the complexities surrounding the diagnosis of serotonin syndrome (SS), through the description of a real-life patient presentation. The management was initiated by a trainee advanced clinical practitioner with the support of a medical registrar. Following the event, six academic databases were searched, none of which yielded any relevant results specific to this case. Therefore, diagnostic criteria have been explored. Applying criteria to this case has demonstrated that the diagnosis of SS was unlikely, yet the treatment given was effective and the patient survived without the need for invasive management.

The prevalence of serotonin syndrome in an intensive care unit: A prospective observational study.

In spite of life-threatening nature of serotonin syndrome (SS), it remains an under-diagnosed condition. The availability of epidemiological data about SS, especially in the ICU setting, may help physicians make early diagnoses and interventions. This was a 6-month prospective study in a medical ICU of a tertiary hospital to find out the prevalence of SS. All consecutive adult patients admitted to the medical ICU were evaluated to see if they fulfilled the Hunter criteria of SS. Patients who met the Hunter criteria were evaluated further for other details. Overall, 309 patients were identified of which 24 (7.8%) met the Hunter criteria. The mean age was 52.4years, and 75% were male. Most patients received two or more serotonergic drugs. Ondansetron was the most common serotonergic drug (58%), followed by tramadol (38%), and cough syrup (dextromethorphan or chlorpheniramine, 21%). None of the patients received a diagnosis of SS by the treating physicians. Chronic obstructive pulmonary disease exacerbation with respiratory failure and metabolic encephalopathy were the two most common admission diagnoses (17% each). Twenty-two patients received cyproheptadine. There were no fatalities. SS is not uncommon in the ICU setting. There is a need to increase awareness among physicians.

Perioperative Serotonin Syndrome Manifesting as Gastrocnemius Myofasciculations: A Case Report

ABSTRACT In perioperative settings where a patient under general anesthesia, presentation of serotonin syndrome might be far from the “classical” description of this potentially fatal condition. A patient who manifested signs of serotonin toxicity during an intravenous anesthetic, remifentanil, is presented. At the time of surgery, the patient was being treated with tramadol for pain management. The patient displayed myofasciculations on both gastrocnemius muscles confirmed electromyographically. All other conventional signs of serotonin syndrome were absent except hypotension and nystagmus. A presumptive diagnosis of serotonin syndrome was made intraoperatively. The symptoms resolved once remifentanil infusion was discontinued in the operating room without incident. Mild-to-moderate perioperative serotonin syndrome may manifest with myofasciculations in gastrocnemius muscles in the settings of no neuromuscular blockade. In spinal surgeries involving intraoperative EMG monitoring, the neuromonitoring team should be aware of this presentation and include serotonin syndrome in the differential diagnosis of unexplained EMG activity.

P.108 Case report: listeria rhombencephalitis in a healthy 64 year old woman

Background: Listeria rhombencephalitis is a rare and serious complication of Listeria monocytogenes infection. We present a case of presumed Listeria rhombencephalitis with dramatic recovery from a highly morbid state. Methods: A previously healthy 64 year old woman with a remote and stable history of a major depressive episode and no history to suggest immune compromise presented with nausea and vomiting followed by the acute onset of diplopia and gait disturbance 28 days after exposure to an identified infectious source of spring rolls and 21 days after a severe diarrheal illness from that exposure. Our patient was evaluated by emergency physicians and general internists over a period of 1 week after the onset of diplopia and gait disturbance and given a diagnosis of serotonin syndrome before receiving a consultation from Neurology. Her presentation featured a deep encephalopathy and an unusual hyperkinetic movement disorder with startle myoclonus, palatal myoclonus and diffuse tremor. Results: Her MRI scan showed FLAIR hyperintensities in the bilateral cerebellum and pons with adjacent pial enhancement, characteristic of Listeria rhombencephalitis. Her CSF showed a lymphocytic pleocytosis with normal chemistry. Conclusions: She recovered dramatically to treatment with IV ampicillin. This case report illustrates the importance of considering Listeria rhombencephalitis in immunocompetent patients with brainstem symptoms following a diarrheal illness.

Incidence of Serotonin Syndrome With Combined Use of Linezolid and Serotonin Reuptake Inhibitors Compared With Linezolid Monotherapy.

Linezolid is a monoamine oxidase inhibitor that may increase the risk of serotonin syndrome in patients receiving combination selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). The objective of this study was to compare the incidence of serotonin syndrome when linezolid was administered alone and in combination with SSRIs or SNRIs. This was a retrospective case-control study of adult inpatients admitted to the University of Iowa Hospitals and Clinics who received linezolid between January 2010 and December 2014. Patients who received linezolid with or within 14 days of an SSRI or SNRI were eligible for inclusion in the combination therapy group. Patients who received linezolid alone were matched by age and gender to patients in the combination therapy group, and 3 monotherapy patients were included for each combination therapy patient. Clinical features consistent with serotonin syndrome were assessed using the Sternbach and Hunter criteria. A total of 348 patients were included in this study, of which 87 received combination therapy and 261 received linezolid monotherapy. One patient given combination therapy (1.1%) and 1 patient given linezolid monotherapy (0.4%) were determined to have a diagnosis of serotonin syndrome (P = 0.438; relative risk, 3.00; 95% confidence interval, 0.19-47.45). In both cases, signs and symptoms of serotonin syndrome reversed upon discontinuation of linezolid therapy. There was no significant difference in the incidence of serotonin syndrome when linezolid was used alone or in combination with an SSRI or SNRI, and the overall incidence of serotonin syndrome was low.

Malignant Syndrome and Serotonin Syndrome in a General Hospital Setting: Clinical Features, Frequency and Prognosis.

Objective The differences in the frequency and clinical features of malignant syndrome (MS) and serotonin syndrome (SS) in same population have only rarely been reported. To report the frequency and clinical features of MS and SS in a general hospital setting. Methods The clinical and laboratory features of patients with MS and those with SS, who were consecutively admitted to Chiba Rosai Hospital, during the past 4.5 years were reviewed. Results Of the 2005 patients admitted, MS was observed in 16 patients (0.8%) and SS in 2 (0.1%). In the 16 patients with MS, the underlying disorder included depression (n = 5), and dementia or parkinsonism (n = 11). The underlying etiology of the 2 patients with SS was depression. In 5 patients, MS was difficult to distinguish from SS because of overlapping symptoms and signs and/or treatments with both neuroleptic and serotoninergic drugs. Of the 16 patients with MS, 1 died, 1 remained wheelchair-bound, 4 were able to walk with assistance, and 10 regained their ability to ambulate independently. The 2 patients with SS recovered after cyproheptadine therapy and were discharged on foot. Conclusion MS occurs more frequently than SS in the general hospital setting. Underlying aetiologies in patients with MS were more common due to dementia or parkinsonism than in patients with psychiatric disorders. The differential diagnosis of MS and SS is often difficult and the diagnostic sensitivities largely differ for each of the diagnostic criteria. As a result, the establishment of new diagnostic criteria that specifically focus on distinguishing MS from SS is therefore required.

Serotonin Syndrome: A Case Report.

Serotonin syndrome is rare but can contribute to a serious and life-threateningillness. It is caused by increasing serotonergic activities. Its incidence tends to increasenowadays because of the use of multiple-drug-regimen. Clinical manifestations ofserotonin syndrome consist of autonomic change with abnormal mental status findingsand abnormal neurologic findings which can vary according to severity. This literaturereports a case of a young woman with serotonin syndrome resulting from drug-to-druginteraction between two selective serotonin receptor antagonists. In this case, she alsohad a high-grade fever and tachycardia due to a concurrent respiratory tract infection.According to the inappropriate degree of fever and presence of inducible myoclonus,diagnosis of serotonin syndrome was made. She had a dramatic response to a 5-HTreceptors antagonist, Cyproheptadine. Serotonin Syndrome itself can be easily overlookedbecause the presenting symptoms can be non-specific. It should be suspected inall patients who currently received serotonergic medicines and have either new medicalor new neurological symptoms.

Neurologic Complications of Commonly Used Drugs in the Hospital Setting.

This chapter reviews the neurologic complications of medications administered in the hospital setting, by class, introducing both common and less common side effects. Detail is devoted to the interaction between pain, analgesia, sedation, and their residual consequences. Antimicrobials are given in nearly every hospital setting, and we review their capacity to produce neurologic sequelae with special devotion to cefepime and the antiviral treatment of human immunodeficiency virus. The management of hemorrhagic stroke has become more complex with the introduction of novel oral anticoagulants, and we provide an update on what is known about reversal of the new oral anticoagulants. Both central and peripheral nervous system complications of immunosuppressants and chemotherapies are reviewed. Because diagnosis is generally based on clinical acumen, alone, neurotoxic syndromes resulting from psychotropic medications may be easily overlooked until severe dysautonomia develops. We include a practical approach to the diagnosis of serotonin syndrome and neuroleptic malignant syndrome.

Serotonin Syndrome in the Intensive Care Unit Following Orthotopic Heart Transplantation: A Case Report

The diagnosis of serotonin syndrome in the ICU population is challenging due to its relative complexity and clinical un- familiarity. Our report is based on a clinical presentation of a 64 year-old female on chronic SSRI therapy who underwent orthotopic heart transplantation (OHT), followed by hyperthermia and autonomic instability. The symptoms were related to the subsequent vasoplegic syndrome requiring methylene blue. The purported offending agents were discontinued and her symptoms improved over the next several hours. Although serotonin syndrome is uncommon and becomes a difficult diagnosis to make, clinicians need to recognize it early.

A Case of Serotonin Syndrome Following Cyproheptadine Withdrawal.

To the Editor: Serotonin syndrome is a life-threatening complication related to the drug interactions involving altered serotonin levels. The majority of cases known so far are related to the overdose of proserotonergic drugs, especially antidepressants such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors. Other drugs such as triptans, opioid analgesics, and antiemetics such as metoclopramide are also documented to cause serotonin syndrome. Very few cases of serotonin syndrome have been reported to be associated with the withdrawal of the serotonergic antagonist with concomitant use of a serotonergic agent.1–3 One such case has been reported due to clozapine withdrawal with concomitant use of citalopram hydrobromide.4 We report a rare case of a patient who developed serotonin syndrome during withdrawal of cyproheptadine with concomitant use of a therapeutic dose of sertraline. Case report. Ms A, a 63-year-old woman, presented to the psychiatry outpatient department with a history of low mood, lethargy, lack of interest in routine activities, loss of appetite, occasional crying spells, and disturbed sleep. Ms A felt hopeless and worthless and often had death wishes. There was no history of any medical illness. She was treated with sertraline 50 mg daily and lorazepam 2 mg at night if needed. After a month, she reported partial improvement, as there were no crying spells or feelings of worthlessness or hopelessness. But, she still had occasional sadness and loss of appetite. Thus, the dose of sertraline was increased to 100 mg and cyproheptadine (syrup) 4 mg twice daily was added to improve her appetite. After 3 weeks, Ms A reported improved appetite, and her depressive symptoms remitted. Cyproheptadine was stopped after 6 weeks, and she continued to receive sertraline 100 mg. Within 24 hours of stopping cyproheptadine, Ms A was brought back to the hospital in a confused state; she was also agitated. Her temperature was 102°F, her pulse was 120 beats/minute, and her blood pressure was 160/100 mm Hg. She also had tremors in her hands. On neurologic examination, muscle twitching (myoclonus) was observed in all the limb muscles with exaggerated deep tendon reflexes. Detailed history revealed no other drug use except sertraline. Laboratory parameters, ie, total blood count, renal and liver function tests, blood sugar, serum electrolytes, electrocardiogram, and chest X-ray, were within normal limits. The brain magnetic resonance image revealed no abnormality except age-related atrophic changes. On the basis of her history, sertraline was stopped and cyproheptadine was restarted at 4 mg every 6 hours, along with lorazepam 2 mg to control the agitation. Ms A improved within 24 to 48 hours. The fever subsided, her blood pressure returned to normal, and she regained her muscle power gradually. There are no clear-cut criteria for the diagnosis of serotonin syndrome, but in the case of Ms A, the diagnosis was made on the basis of her symptom profile, the exclusion of possible medical causes, her history of cyproheptadine withdrawal, and her improvement with reinstitution of cyproheptadine. Ms A had serotonin syndrome, which developed after sudden withdrawal of cyproheptadine (5HT2 antagonist) due to unopposed action of sertraline (serotonergic agent) even at a therapeutic dosage. Withdrawal of cyprohepatadine led to a sudden increase in the levels of serotonin, leading to serotonin syndrome.

Serotonin Syndrome During Opioid Therapy – the Underdiagnosed Adverse Interaction and Its Implications for the Management of Chronic Pain

The complexity of chronic pain demands interdisciplinary treatment approaches, however, complex analgesic regimens pose risks for potential adverse drug interactions. Effective management of chronic pain is further complicated by the presence of associated comorbidities, especially depression. As a result, is common for these patients to be prescribed opioid analgesics with antidepressant medications. The first ones may significantly affect serotonin kinetics in the presence of other serotoninergic agents, increasing intrasynaptic serotonin levels. Serotonin syndrome (SS) is a rare and potentially life-threatening iatrogenic complication of serotoninergic polypharmacy. It typically appears after initiation or dose escalation of the offending agent to a regimen that generally includes other serotoninergic agents (like antidepressants drugs and opioids) and all drugs that directly or indirectly increase central serotonin neurotransmission at postsynaptic 5-HT1A and 5-HT2A receptors can produce serotonin syndrome. Individual vulnerability appears to play a role in the development of this complication. Aims To report a clinical case of SS in a 62-yr-old woman with postmastectomy pain syndrome, resulting from the addition of duloxetine to a medication regimen of sertraline and fentanyl. The review of the literature serves as an overview of the epidemiology, pathophysiology, clinical features, differential diagnosis and prevention of SS. Methods Literature review and clinical case description. Results and Conclusions To our knowledge, few case-reports have been published including duloxetine as a precipitant agent of SS. Clinicians should be alert to this potential iatrogenic adverse interaction of serotoninergic antidepressants with commonly prescribed opioid analgesics in chronic pain patients.

Incidence of Serotonin Syndrome in Patients Treated with Fentanyl on Serotonergic Agents

Background: There has been a recent surge in the literature highlighting the association of fentanyl as precipitating serotonin syndrome in patients on a serotonergic agent. Objective: The purpose of our study was to understand the incidence of serotonin syndrome in patients who receive fentanyl while on serotonergic agents. Study Design: This retrospective analysis was conducted from 2012 to 2013 after approval from the Institutional Review Board. We searched for all patients that had received a serotonergic agent and were admitted to the hospital during the study period. Next, we split these patients into 2 groups by placing all patients who had received fentanyl and a serotonergic agent into one group. We then searched for any of the Hunter Serotonin Toxicity Criteria in the records of patients that had received both fentanyl and a serotonergic agent. Further, we searched for all patients with serotonin syndrome mentioned in their records. Setting: This study was conducted at a 900 bed tertiary care academic center. Results: Over the 2 year study period, 112,045 patients were on a serotonergic agent, and 4,538 of these patients were treated with both fentanyl and a serotonergic agent. A search for Hunter’s Criteria through the records of the patients receiving both fentanyl and a serotonergic agent revealed 23 patients had been documented with some of these symptoms. On detailed chart review, only 4 [95% CI 1 – 10] of these patients truly met Hunter’s Criteria for serotonin syndrome. We then searched all admissions for a diagnosis code of serotonin syndrome during the study period. Five additional cases of serotonin syndrome were found, but none of these patients were treated with fentanyl. Limitations: Some of the limitations of our study include that it represents a single institution, although it is a large academic center. An inherent limitation may be the under diagnosis of serotonin syndrome. Conclusion: The incidence of serotonin syndrome in patients who receive both fentanyl and a serotonergic agent is low. Key words: Fentanyl, serotonin syndrome, serotonergic drugs, opioids, SSRI, antidepressant

Serotonin syndrome after therapeutic hypothermia for cardiac arrest: A case series

AimTo describe causes, manifestations, and diagnosis of serotonin syndrome following therapeutic hypothermia (TH) after cardiac arrest. MethodsRetrospective case series from a tertiary academic medical center. ResultsThree male patients suffered witnessed out-of-hospital cardiac arrests and were treated with induced TH. Initial cardiac rhythms included asystole in two and ventricular fibrillation in one. Following completion of rewarming, all three developed neurological signs unexpected for their clinical condition. These included rigidity, hyperreflexia, diffuse tremors, ankle clonus, and marked agitated delirium. Patients also were febrile, hypertensive, and tachycardic. A diagnosis of serotonin syndrome was made in all cases and serotonergic medications were discontinued. All three patients recovered consciousness and two made a full neurological recovery. One patient remained dependent on others for activities of daily living at the time of hospital discharge because of short-term memory impairment. ConclusionsUnexpected neurologic findings and prolonged high fever following recovery from TH can be manifestations of serotonin syndrome rather than post-cardiac arrest anoxic brain injury.

Fluoxetine-Induced Atypical Serotonin Syndrome with Hallucinations Masquerading as a Parkinsonian Syndrome

Objective: To report a unique case of fluoxetine overdose leading to serotonin syndrome with auditory and complex visual hallucinations. This case also demonstrates serotonin syndrome may mimic a Parkinsonian syndrome, which is poorly described in the literature. Case Summary: A 65-year-old gentleman, undergoing evaluation for possible Parkinsonian syndrome with bradykinesia and rigidity presented to the emergency department with additional complaints of weakness, fatigue, flushing, and complex visual and auditory hallucinations. Chart review revealed he was unintentionally overdosed with fluoxetine to a total daily dose of 160 mg. Examination revealed tachycardia, diaphoresis, significant mydriasis, and visual hallucinations. Initial workup was unremarkable. Poison control recommended discontinuation of the fluoxetine and in follow up he reported resolution of all symptoms. Discussion: This case describes serotonin syndrome as the result of chronic fluoxetine overdose masquerading as a Parkinsonian syndrome. This patient also experienced auditory and visual hallucinations that resolved with cessation of fluoxetine, adverse effects which are relatively uncommon. The likelihood the patient’s symptoms were the result of fluoxetine intoxication is probable, as assessed by the Naranjo Adverse Drug Reaction (ADR) probability scale. Conclusions: Chronic fluoxetine overdose can lead to serotonin syndrome, as well as, several rare adverse effects including a Parkinsonian syndrome, complex visual, and auditory hallucinations. A high index of suspicion is necessary for diagnosis of serotonin syndrome, particularly in mild cases. Most cases can be prevented with careful medication reconciliation.

Retrospective review of a case of serotonin syndrome after discontinuation of risperidone: Was withdrawal neuroleptic malignant syndrome missed?

INTRODUCTION The job of the pharmacist rarely involves evaluating diagnostic impressions or making definitive diagnoses. However, the pharmacist may often be called upon to give his or her assessment of a clinical picture when drugrelated or drug-induced factors may be at play. In addition, pharmacists may be called upon to give therapy recommendations, frequently evaluating appropriate dosing, drug interactions and even therapeutic endpoints of medications. As patient and drug-regimen complexity increase, the ability of the pharmacist to give valuable input to the diagnostic impression or assessment of drugrelated factors regarding a patient’s clinical presentation becomes paramount. This may be particularly true in the context of mental health patients treated with more than one psychotropic agent.

Headache as a presenting feature in patients with serotonin syndrome: A case series

Serotonin syndrome (SS) is a drug-induced constellation of various clinical features that result from excess central serotonergic tone. The clinical features range from barely perceptible to life-threatening conditions. We describe four patients with acute headache (four days to three weeks) who were receiving serotonergic drugs for other indications. There was a temporal relation between the administration of the serotonergic drugs and the development of the headaches. All four patients fulfilled the Hunter Serotonin Toxicity Criteria for SS. In parallel, two patients fulfilled the Sternbach's criteria for SS. Discontinuation of the serotonergic drugs and the administration of cyprohepatadine led to complete improvement in three to seven days in all four patients. A review of the literature suggests that some overlaps exist in the pathophysiology between SS and headache disorders, including medication-overuse headache. The overlap is also in the management. The drugs found to be effective in SS (cyproheptadine, chlorpromazine, olanzapine, etc.) are also known to have positive effects on some headache disorders. Physicians should consider the diagnosis of SS in patients with new onset or worsening headache after the addition of serotonergic drugs, especially in the presence of objective signs on examination suggestive of the disorder such as tremor, fever, hyperreflexia, diaphoresis or tachycardia.

Serotonin syndrome manifesting as patient movement during total intravenous anesthesia with propofol and remifentanil

A patient who manifested signs of serotonin syndrome during an intravenous anesthetic with remifentanil and propofol is presented. The patient displayed lower extremity clonus, nystagmus, and diaphoresis. At the time of surgery, the patient was being treated with fluoxetine (a selective serotonin reuptake inhibitor). A presumptive diagnosis of serotonin syndrome was made intraoperatively and all opioids were discontinued. His symptoms resolved in the Postanesthesia Care Unit without incident.

Serotonin Syndrome in a Sertraline-Treated Man Taking NyQuil Containing Dextromethorphan for Cold

To the Editor: Serotonin syndrome is defined as a clinical triad of autonomic hyperactivity, mental status changes, and neuromuscular changes, though the presentation could be very varied.1,2 We present the case of a man receiving sertraline for depression who developed serotonin syndrome after taking the over-the-counter medication NyQuil for treatment of cold symptoms. Case report. Mr A, a 46-year-old thinly built man, had received sertraline 100 mg/d for depression for 2 years. His medical history was significant for diabetes mellitus, for which he was being treated with metformin 500 mg twice daily; hypothyroidism, for which he was receiving levothyroxine 100 μg; and chronic low back pain, for which he was not taking medication. After he developed cough, congestion, and insomnia, he called his primary care physician for an appointment. The physician’s office recommended his taking over-the-counter (OTC) medications for congestion until he was to be seen the following day. Thus, he started taking OTC NyQuil containing dextromethorphan; in 1 night, he drank 240 mL of the liquid. The next day, Mr A presented to the emergency department with confusion, shivering, agitation, fever, diaphoresis, stupor, hyperreflexia, and diarrhea. Examination found tachycardia with pulse of 110 bpm, blood pressure of 155/89 mm Hg, tachypnea (24 breaths/min), and hyperthermia (39.0°C). Mydriasis and hyperactive bowel sounds were appreciated. Neurologic examination was positive for hyperreflexia (which was greater in the lower than in the upper extremities), tremor, and rigidity. S1 and S2 heart sounds showed no abnormalities, and breath sounds were clear on auscultation bilaterally. His laboratory test results were mostly within normal limits except for findings of metabolic acidosis and increased blood urea nitrogen/creatinine levels. White blood cell (WBC) count was 9,000/μL . Urine drug screen was negative for any illicit substances. No alcohol was detected in blood. Head computed tomographic scan and a chest x-ray revealed no abnormalities. A diagnosis of serotonin syndrome was suspected on the basis of the clinical picture. The patient met Sternbach criteria for serotonin syndrome3; Sternbach criteria were used as there was addition of a serotonergic agent the night before. He was admitted to the intensive care unit, at which time his sertraline was discontinued. The psychiatry department was consulted, and pertinent history regarding the use of dextromethorphan was elicited. Mr A improved with administration of diazepam 1 mg every 4 hours as needed and intravenous fluids. Symptoms resolved within 2 days, and the patient was later discharged. His sertraline was discontinued and was replaced with mirtazapine. In patients with serotonin syndrome, autonomic symptoms may range from fever, hyperthermia, and diaphoresis to tachycardia, tachypnea, flushing, diarrhea, hypertension, and dyspnea. Mental status changes may include confusion and coma when serotonin syndrome is severe and anxiety, agitation, restlessness, and insomnia when it is less severe. Neuromuscular symptoms may include clonus, hypertonia, tremor, shivering, and hyperreflexia.1,2 Medications that could be associated with serotonin syndrome include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors; analgesics such as fentanyl, methadone, and tramadol; antiemetics such as ondansetron and metoclopramide; triptans; herbal supplements such as St. John’s wort and ginseng; illicit drugs such as cocaine, ecstasy, and LSD; and over-the-counter medications such as dextromethorphan.1,2 Differentiation should also be made from other syndromes such as the neuroleptic malignant syndrome (NMS), anticholinergic poisoning, and malignant hyperthermia. Neuroleptic malignant syndrome, which is caused by excess of dopamine, starts with muscular rigidity followed by hyperthermia. Bradykinesia is prominent in NMS, whereas serotonin syndrome consists of hyperkinesias. In NMS, symptoms develop over days, whereas in serotonin syndrome, the onset and resolution of symptoms occur within hours.1 Diagnosis can be made by Sternbach criteria3 or Hunter criteria.4 Sternbach criteria consist of the following: recent addition of a serotonergic agent; no addition of a neuroleptic agent; absence of other etiologies (infection, substance abuse, withdrawal); and 3 or more symptoms including autonomic symptoms, mental status changes, and neuromuscular symptoms.3 Hunter criteria comprise the presence of a serotonergic agent and any one symptom including spontaneous clonus, inducible clonus with agitation and diaphoresis, ocular clonus and agitation or diaphoresis, ocular clonus or inducible clonus, tremor and hyperreflexia, and hyperthermia and hypertonia and ocular/inducible clonus.4 Dextromethorphan is a moderate serotonin reuptake inhibitor.5–7 Dextromethorphan also promotes serotonin release.7 In addition, N-methyl-d-aspartate receptor antagonism by dextromethorphan is associated with postsynaptic 5-HT2A stimulation.7 Dextromethorphan is metabolized by the cytochrome P450 (CYP) 2D6 pathway.8 Sertraline, an SSRI, is a moderate inhibitor of the CYP2D6 pathway.9 Hence, sertraline can increase levels of dextromethorphan and cause increased serotonin when the 2 agents are used concomitantly. Patients taking SSRIs should be warned about the increased chances of serotonin syndrome when also taking over-the-counter medications containing dextromethorphan. Once recognized, serotonin syndrome should be aggressively treated and offending agents should be removed.