Serotonin syndrome treated with cyproheptadine using NPi from a digital pupillometer as a therapeutic indicator: A case report.

RATIONALE: Serotonin syndrome is a potentially life-threatening condition resulting from the use of antidepressants, their interactions with other serotonergic medications, or poisoning. It presents with a triad of psychiatric, dysautonomic, and neurological symptoms and is sometimes fatal. While cyproheptadine is a specific treatment option, the optimal duration of its administration remains unclear. The purpose of this report is to quantitatively assess the endpoints of serotonin syndrome treatment. Based on the hypothesis that neurological pupil index (NPi) on a digital pupil recorder would correlate with the severity of the serotonin syndrome, we administered cyproheptadine using NPi as an indicator. PATIENT CONCERNS: A patient with a history of depression was brought to our hospital after he overdosed on 251 tablets of serotonin and noradrenaline reuptake inhibitors. DIAGNOSES: On day 3, the patient was diagnosed with serotonin syndrome. INTERVENTIONS: Cyproheptadine syrup was administered at 4 mg every 4 hours. The NPi of the automated pupillometer was simultaneously measured. On day 5, the NPi exceeded 3.0 cyproheptadine was discontinued. OUTCOMES: The patient was discharged on day 7. LESSONS: The lack of considerable improvement during the treatment period suggests that the patient may have improved on his own. In this case, the relationship between NPi and the severity of serotonin syndrome could not be determined.

A Case Series of 11 Patients With Subacute Serotonin Syndrome.

BACKGROUND: Serotonin syndrome is an acute, life-threatening illness characterized by mental status changes, neuromuscular symptoms, and autonomic instability. Some patients taking serotonergic antidepressants have been noted to have unexplained mental status changes and/or neuromuscular changes without autonomic instability raising the possibility of a more chronic or attenuated form of serotonin syndrome. OBJECTIVE: Assessment of antidepressant blood levels to support the diagnosis of a subacute serotonin syndrome. METHODS: At a tertiary psychiatric outpatient clinic, patients with unexplained mental status and/or neuromuscular changes without autonomic instability had antidepressant blood levels assessed. RESULTS: Eleven patients were identified with signs and symptoms partially consistent with serotonin syndrome. Nine patients had cognitive changes, while four patients had motor changes, and three patients had psychosis. All patients had elevated blood levels of a single serotonergic antidepressant. Limited follow-up suggests that symptoms improve with reduction of antidepressant medication. CONCLUSIONS: These cases suggest that a more chronic, attenuated form of serotonin syndrome exists. Diagnostic criteria are proposed for a distinct clinical entity: subacute serotonin syndrome (SSS). Further research is required to validate these criteria. Clinicians should consider drawing antidepressant levels for patients with symptoms and signs suggestive of SSS-especially those at increased vulnerability for excessive serotonergic agonism. Given the high prevalence of antidepressant medication use, the awareness of SSS could lead to improved patient outcomes and public health.

Fentanyl-Induced Serotonin Syndrome 5 Days After Cessation of Serotonergic Agents: A Case Report.

A 21-year-old patient with intellectual disability was admitted for gastroenteritis due to serotonergic medication overdose, and subsequently developed serotonin syndrome. Her symptoms initially improved after the cessation of serotonergic medications, but worsened 5 days later after fentanyl administration during general anesthesia. On emergence, she had convulsions and was nonresponsive. Subsequent imaging and electroencephalography did not demonstrate intracranial pathology or seizure activity. We suspect she had an exacerbation of her serotonin syndrome. She recovered successfully after supportive care. This case demonstrates that common medications used during anesthesia such as fentanyl can provoke serotonin syndrome, even several days after serotonergic drug discontinuation.

The Neuropsychiatric Safety Profile of Lasmiditan: A Comparative Disproportionality Analysis with Triptans.

Migraine constitutes the world's second-leading cause of disability. Triptans, as serotonin 5-HT1B/1D receptor agonists, remain the first-line treatment, despite discouraged use in individuals at high cardiovascular risk. Lasmiditan, a selective lipophilic 5-HT1F agonist without vasoconstrictive effects, is an emerging option. We aimed to investigate the safety profile of lasmiditan in the WHO pharmacovigilance database (VigiBase®) using a comparative disproportionality analysis with triptans. VigiBase® was queried for all reports involving lasmiditan and triptans. Disproportionality analyses relied on the calculation of the information component (IC), for which 95% confidence interval (CI) lower bound positivity was required for signal detection. We obtained 826 reports involving lasmiditan. Overall, 10 adverse drug reaction classes were disproportionately reported with triptans, while only neurological (IC 1.6; 95% CI 1.5-1.7) and psychiatric (IC 1.5; 95% CI 1.3-1.7) disorders were disproportionately reported with lasmiditan. Sedation, serotonin syndrome, euphoric mood, and autoscopy had the strongest signals. When compared with triptans, 19 out of 22 neuropsychiatric signals persisted. The results of our analysis provide a more precise semiology of the neuropsychiatric effects of lasmiditan, with symptoms such as autoscopy and panic attacks. The cardiovascular adverse drug reaction risk with triptans was confirmed. In contrast, caution is warranted with lasmiditan use in patients with neurological or psychiatric comorbidities or serotonin syndrome risk. Our study was hindered by pharmacovigilance flaws, and further studies should help in validating these results. Our findings suggest that lasmiditan is a safe alternative for migraine treatment, especially when the neuropsychiatric risk is outweighed by the cardiovascular burden.

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.

Dexmedetomidine in the treatment of toxicologic conditions: a systematic review and review of the toxicology investigators consortium database.

INTRODUCTION: Dexmedetomidine is an alpha-2 adrenoceptor agonist which is widely used for sedation. Dexmedetomidine does not suppress the respiratory drive and produces a state of cooperative sedation; it may be associated with beneficial outcomes in the general critical care population. The role of dexmedetomidine in the treatment of toxicologic conditions (excluding alcohol withdrawal) is unclear. OBJECTIVES: To critically assess and summarize the literature regarding the use of dexmedetomidine in toxicologic conditions other than alcohol withdrawal. METHODS: We performed a systematic review of the medical literature to identify all existing evidence regarding the use of dexmedetomidine for toxicologic conditions. We excluded reviews and commentary, studies reporting exclusively on alcohol withdrawal, and studies reporting the use of dexmedetomidine to treat iatrogenic sedative withdrawal in the intensive care unit. We also performed a review of the Toxicology Investigators Consortium (ToxIC) database for patients treated with dexmedetomidine. RESULTS: We identified 98 studies meeting inclusion criteria; 87 of these were case reports or case series, representing 99 unique cases. Eleven articles with other designs were identified, which included 138 patients treated with dexmedetomidine for toxicologic conditions. Ninety-three cases from the ToxIC registry met inclusion criteria. Common indications for dexmedetomidine included stimulant intoxication, sedative withdrawal, serotonin syndrome, antimuscarinic toxidrome, opioid withdrawal, and cannabinoid intoxication. Dexmedetomidine was usually administered by continuous infusion; bolus administration was reported in a minority of cases. Adverse effects were uncommon. The quality of evidence was generally low, given the preponderance of case reports, the rate of missing or poorly reported data, and the near-universal co-administration of other sedatives. TREATMENT OF STIMULANT POISONING: Fifty-nine patients with stimulant poisoning were treated with dexmedetomidine. There was reasonably good evidence that dexmedetomidine was helpful in the treatment of stimulant poisoning. TREATMENT OF SEDATIVE WITHDRAWAL: Twenty-two patients with sedative withdrawal were treated with dexmedetomidine. Several case reports of very high-quality suggested efficacy of dexmedetomidine for this indication, particularly for baclofen withdrawal. TREATMENT OF SEROTONIN SYNDROME: Twenty-six patients with serotonin syndrome were treated with dexmedetomidine. This evidence was of lower quality due to missing clinical details, potential overdiagnosis of serotonin syndrome, and near-universal concomitant treatment with other sedatives. TREATMENT OF ANTIMUSCARINIC POISONING: Forty-two patients with antimuscarinic poisoning were treated with dexmedetomidine. This evidence was of low quality and was limited by infrequent use of the preferred antidote, physostigmine. TREATMENT OF OPIOID WITHDRAWAL: Forty-four patients with opioid withdrawal were treated with dexmedetomidine. This evidence was of low quality due to missing clinical details and near-universal concomitant treatment with other agents. The one high-quality trial reported the use of dexmedetomidine in ultra-rapid opioid detoxification, which is not indicated in modern practice. TREATMENT OF CANNABINOID INTOXICATION: Five patients with cannabinoid intoxication were treated with dexmedetomidine. No definite conclusion can be drawn from the limited available evidence. DISCUSSION: It is important to distinguish between the use of dexmedetomidine as a general sedative, which is likely to increase as the overall utilization of dexmedetomidine in critical care settings increases, and the use of dexmedetomidine as a specific pharmacologic treatment for a toxicologic condition. Well-established pharmacologic data from animal and human studies suggest dexmedetomidine counteracts stimulant-induced norepinephrine release. The mechanism by which dexmedetomidine treats sedative withdrawal is unclear. Some animal data show that dexmedetomidine may indirectly suppress serotonin release, which may suggest a role for dexmedetomidine in this condition. CONCLUSIONS: There is a small and generally low-quality body of evidence which suggests that dexmedetomidine may be helpful in the treatment of certain toxicologic conditions, particularly stimulant intoxication and sedative withdrawal. Further high-quality research is needed to clarify the role of dexmedetomidine in patients with toxicologic conditions.

Safety of Ketamine Augmentation to Monoamine Oxidase Inhibitors in Treatment-Resistant Depression: A Systematic Literature Review and Case Series.

Objective: Ketamine is increasingly prescribed for treatment-resistant depression (TRD), often as add-on to regular antidepressants. Augmentation of ketamine to monoamine oxidase inhibitors (MAOIs) is advised against, as this practice might increase blood pressure or cause serotonin syndrome. Despite the potential relevance for patients, little is known about actual side effects of combined use. We summarize literature on the safety and add results of our case series.Evidence Review: PubMed and Embase were searched from inception to July 2021 for English-language articles describing concomitant use of ketamine and MAOIs. The search strategy included terms for "ketamine" AND "monoamine oxidase inhibitor" including generic and brand names. Additionally, we describe the safety of twice weekly oral esketamine administration over the course of 5 weeks to 9 months in 8 TRD patients using MAOIs.Findings: After deduplication, we screened 138 articles and assessed 43 full texts. Twelve studies were included with a total of 39 patients receiving ketamine and MAOIs. Blood pressure and heart rate increased in multiple cases, though this was deemed clinically insignificant in all but 1 patient. No signs of hypertensive crisis or serotonin syndrome were observed. In our case series, we observed minor elevations in blood pressure and heart rate and no serious adverse events.Conclusions and Relevance: The results suggest that combined use of MAOIs and esketamine is less prone to severe side effects than presumed. The investigated sample size was small, and prescribed doses of MAOIs were relatively low. Further research is required before definite conclusions about the safety of this combination can be drawn.

Serotonin Syndrome After Treatment of Nausea and Vomiting in Pregnancy.

BACKGROUND: Nausea and vomiting in pregnancy often require pharmacotherapy for symptom management. Serotonin syndrome is a rare clinical entity that can be precipitated by the medications used to treat nausea and vomiting in pregnancy. CASE: A 35-year-old pregnant individual with a history of hyperemesis gravidarum in an earlier pregnancy requiring prolonged hospitalization presented with nausea and vomiting at 7 weeks of gestation. She was incidentally found to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection when she was universally screened at the time of admission. She required pharmacotherapy, including prochlorperazine and ondansetron for treatment of nausea as well as sumatriptan for migraine. She developed acute spasticity, autonomic dysfunction, and temperature rise, precipitated by antiemetic therapy, consistent with serotonin syndrome. The syndrome resolved with supportive care and benzodiazepines. CONCLUSION: Serotonin syndrome is a serious clinical entity that can be provoked by the pharmacotherapy given to treat nausea and vomiting in pregnancy. This medical emergency requires early recognition and prompt management.

Postoperative Serotonin Syndrome Following Administration of Preoperative Intrapulmonary Methylene Blue and Intraoperative Granisetron: A Case Report.

BACKGROUND Methylene blue (MB), which is often used perioperatively, is a potent monoamine oxidase inhibitor that can strongly block the clearance of extracellular serotonin. Granisetron, a serotonin receptor subtype 3 (5-HT3) antagonist, is an antiemetic used to prevent or treat postoperative nausea and vomiting (PONV). Through its antagonism, granisetron can increase the extracellular serotonin concentration. Serotonin syndrome is a potentially life-threatening condition resulting from a drug reaction that affects serotonin levels. This report is of a 50-year-old woman with postoperative serotonin syndrome following co-administration of preoperative intrapulmonary methylene blue and intraoperative granisetron. CASE REPORT A 50-year-old woman with well-controlled gastroesophageal regurgitation disease presented under impression of lung cancer. She received a computed tomography (CT)-guided localization followed by video-assisted thoracic surgery under endotracheal general anesthesia. The surgery was completed uneventfully. Her postoperative course was significant for serotonin syndrome, likely triggered by co-administration of preoperative intrapulmonary MB for tumor localization and intraoperative granisetron. Other differential diagnoses were ruled out. Her management was primarily supportive, using benzodiazepine administration, and resulted in full neurologic recovery. CONCLUSIONS Intrapulmonary MB can lead to serotonin syndrome in combination with 5HT-3 antagonists when used for preoperative tumor localization. Because both MB and 5-HT3 antagonists are being widely used clinically at present, this report has highlighted that physicians, surgeons, and anesthesiologists should be aware of serotonin syndrome, its presenting features, and management, and its association with the use of methylene blue and 5-HT3 receptor antagonists, including granisetron.

Antidepressant-induced serotonin syndrome in older patients: a cross-sectional study.

BACKGROUND: Widespread prescription of antidepressants and their resulting role in serotonin syndrome (SS) are of great importance for clinical practice in the elderly. This study aims to investigate possible associations of antidepressant drug-induced SS with related variables in these patients. METHODS: A total of 238 older adults using antidepressants were included. Patients who fulfilled the Hunter Serotonin Toxicity Criteria (HSTC) for SS were considered as the clinical groups (mild, moderate, or severe), and those who did not as the control group. We recorded all patients' demographic and clinical characteristics, including age, gender, comorbidity index, number of medications, daily equivalent dose of the relevant antidepressant according to fluoxetine per day, electrocardiogram test results, laboratory results, and management. RESULTS: The mean age of all patients was 75.4 ± 7.6 years and 63.4% were female. Sixty patients had SS, while 178 patients did not. There was a significant difference between those with and without SS in terms of gender, frequency of combination antidepressant therapy, and daily equivalent antidepressant dose (P < 0.05). The most common diagnostic findings in SS patients were tremor and hyperreflexia and 31.7% was mild, and moderate in 68.3% with higher median age and number of medications (P < 0.041). Antidepressants were discontinued in all patients regardless of severity, of whom 71.7% were treated with benzodiazepines and 36.7% with cyproheptadine. After adjusting for age and sex, association with use of SSRI + SNRI, use of any combination therapy, and daily equivalent dose remained significant. CONCLUSIONS: The widespread single or combined use of antidepressants in older adults represents an increased clinical concern for SS and physicians should be aware of this drug-related complication in older patients.

Antiepileptic drugs and serotonin syndrome- A systematic review of case series and case reports.

Serotonin syndrome (SS) is a drug­induced, potentially fatal, clinical syndrome resulting from drugs that have serotonergic properties. Several antiepileptic drugs (AEDs) are known to have serotonergic properties and it can be hypothesized that such AEDs can cause SS. This study aims to review the literature on SS in patients receiving AEDs. We performed a systematic review of Scopus and MEDLINE/PUBMED for case reports and case series of SS where patients had received at least one AED at the onset of symptoms. The cases published in the English literature between 1 January 1991 and 1 April 2021 were included. Initial search identified 1263 articles of which 63 (76 patients) were included in the final analysis. Most of the included cases (53 cases, 70%) have been published in the last 10 years. The mean age of the 76 patients was 40.6 ± 17.8 years, and 51% of cases were females. These patients had been exposed to a total of 8 different types of AEDs. Valproic acid was the most common drug (29, 38%), followed by lamotrigine (22, 29%), gabapentin (16, 21%), pregabalin (seven, 9%), topiramate (five, 7%) and carbamazepine (two, 3%). There has been one case each with phenytoin and oxcarbazepine. Seven (9%) patients received more than one AEDs. Most patients (67, 88%) also received other serotoninergic agents. Only nine (12%) patients were on AEDs alone. The most common clinical condition for using AEDs was psychiatric disorders (36 patients, 47.3%), followed by migraine (17, 22.4%), other painful conditions (15, 19.7%), epilepsy (7, 9.2%), and perioperative conditions (8, 10.5%). Death was reported in two patients. We suggest that AEDs, because of their serotonergic properties, may induce SS, especially in patients who are on another serotonergic agent.

Postoperative Serotonin Syndrome Following Methylene Blue Administration for Vasoplegia After Cardiac Surgery: A Case Report and Review of the Literature.

Serotonin syndrome is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. The increasing incidence of this condition is thought to parallel the increasing use of serotonergic agents in medical practice. The selective serotonin reuptake inhibitors are perhaps the most commonly implicated group of medications associated with serotonin syndrome. This case report describes the occurrence of postoperative serotonin syndrome in a patient on long-term sertraline who underwent coronary artery bypass graft and was treated with methylene blue for perioperative vasoplegia. It delineates the various clinical features commonly encountered and illustrates the recommended management modalities, including prevention, for this potentially lethal medical emergency. With prompt diagnosis and expeditious treatment, the patient has had full recovery.

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.

5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology.

L-5-hydroxytryptophan (5-HTP) is both a drug and a natural component of some dietary supplements. 5-HTP is produced from tryptophan by tryptophan hydroxylase (TPH), which is present in two isoforms (TPH1 and TPH2). Decarboxylation of 5-HTP yields serotonin (5-hydroxytryptamine, 5-HT) that is further transformed to melatonin (N-acetyl-5-methoxytryptamine). 5-HTP plays a major role both in neurologic and metabolic diseases and its synthesis from tryptophan represents the limiting step in serotonin and melatonin biosynthesis. In this review, after an look at the main natural sources of 5-HTP, the chemical analysis and synthesis, biosynthesis and microbial production of 5-HTP by molecular engineering will be described. The physiological effects of 5-HTP are discussed in both animal studies and human clinical trials. The physiological role of 5-HTP in the treatment of depression, anxiety, panic, sleep disorders, obesity, myoclonus and serotonin syndrome are also discussed. 5-HTP toxicity and the occurrence of toxic impurities present in tryptophan and 5-HTP preparations are also discussed.

Serotonin Syndrome Following Terbutaline Administration in a Heart Transplant Patient on Multiple Inotropic Agents: A Case Report.

The significance of serotonin syndrome due to drug-drug interactions has emerged as a prominent consideration when the effects of polypharmacy are reviewed. The emergence of the selective serotonin reuptake inhibitors has most likely fueled the increased reporting of serotonin syndrome in the literature, leading to increased awareness of this phenomenon. However, their presence is not necessarily inclusive to a case and the utilization of agents precipitating an occurrence may be unavoidable. We report a case of serotonin syndrome occurring in a heart transplant patient without the presence of any of the usual suspect agents involved. In the postoperative course, the patient developed cardiogenic shock with vasoplegia requiring continuation of inotropic therapy along with vasopressor support of epinephrine. Oral terbutaline was begun for hemodynamic improvement. The patient's tenuous mental status rapidly deteriorated after addition of the terbutaline, with symptoms consistent with serotonin syndrome. Administration of cyproheptadine, a known reversal agent for serotonin toxicity, rapidly alleviated the adverse symptoms.

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.

Development of severe serotonin syndrome from acute ingestion of vilazodone without co-ingestion.

Vilazodone is a selective serotonin reuptake inhibitor (SSRI) that was introduced to the market in 2011. It has a novel mechanism combining serotonin reuptake and partial agonism of 5HT-1 receptors. It has gained popularity in treating first generation SSRI-resistant depression. There has been little description in the literature of adult overdose. We are describing a 21-year-old female with an intentional overdose of 400 mg of vilazodone. This patient progressively developed worsening serotonin syndrome, which was resistant to aggressive benzodiazepine administration. The patient required sedation with propofol and phenobarbital to control serotonin syndrome. Patient required continued sedation for 36 h post-ingestion, with subsequent extubation and return to normal mental status. We detail an atypical case of a novel SSRI overdose with the treatment regimen used.

Serotonin syndrome from sertraline monotherapy.

Serotonin syndrome (SS) is a rare, potentially life-threatening adverse drug reaction. Selective serotonin reuptake inhibitors (SSRIs) are among a number of pharmaceuticals that all contribute to SS, but SS caused by SSRI monotherapy is rare. We present a case of probable sertraline-induced SS. A 36-year-old male presented to the emergency department four times in one week with a constellation of autonomic and neuromuscular symptoms. He had been taking sertraline at a therapeutic dose for less than three months. Moderate SS was diagnosed using the Hunter criteria during the fourth visit, when it was seen that he had hyperreflexia and inducible ankle clonus. The patient's symptoms resolved within 24 hours with lorazepam, intravenous fluids, and discontinuation of sertraline. In the emergency department it is important to have a high clinical suspicion for SS even if the patient is taking SSRI monotherapy at therapeutic doses.