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.

Serotonergic neurotransmission mediated cognitive dysfunction in two mouse models of sepsis-associated encephalopathy.

BACKGROUND: Patients with sepsis-associated encephalopathy (SAE) often exhibit cognitive impairments. Despite this, the underlying mechanisms of SAE remain largely unexplored. Here, we explored the role of serotonergic neurotransmission in cognitive dysfunction of two mouse models of SAE. METHODS: The mouse models of SAE were established by injection of lipopolysaccharide (LPS, 10 mg/kg, intraperitoneal) and cecal ligation puncture (CLP) respectively. Barnes maze, new object recognition test and open field test were used to evaluate the effects of fluoxetine (selective serotonin reuptake inhibitor) and cyproheptadine (nonselective 5-HT2 receptor antagonist) on cognition and motor activity of mice. Additionally, WAY100635 (5-HT1A receptor antagonist) was co-administered with fluoxetine to explore the mechanism underlying effect of fluoxetine on cognitive impairments of SAE. Enzyme-linked immunosorbent assay (ELISA) was performed to determine 5-HT levels in hippocampus, brainstem and frontal lobe of experimental groups. RESULTS: Both LPS-induced sepsis and CLP induced sepsis resulted in a notable learning deficit. Fluoxetine ameliorated, while cyproheptadine aggravated, cognitive impairment in two classic mouse models of SAE. The cognition-enhancing effect of fluoxetine is reversed by WAY100635. Decreased 5-HT levels in hippocampus, brainstem and frontal lobe were observed in LPS septic model and CLP septic model. Notably, both fluoxetine and cyproheptadine significantly increased 5-HT levels in those brain regions in LPS septic model. Additionally, fluoxetine significantly increased 5-HT levels in frontal lobe of CLP septic model. CONCLUSIONS: Our study demonstrated that serotonergic neurotransmission plays a significant role in mechanisms underlying cognitive impairment in SAE. These findings contribute to identification of novel targets to prevent and arrest cognitive impairment in SAE.

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.

The role of serotonin in pathogenesis of unclassified irritable bowel syndrome.

The pathogenesis of irritable bowel syndrome (IBS) has not been clearly understood. Numerous factors, including neurotransmitters, can interfere with the functions of the digestive tract. AIM: The aim of present study was to determine the secretion and metabolism of serotonin in patients with unclassified irritable bowel syndrome (IBS-U). MATERIALS AND METHODS: The study included 50 healthy subjects (Controls) and 50 patients with IBS-U, diagnosed according to Rome IV Criteria of functional gastrointestinal disorders. The severity of gastrointestinal symptoms was assessed using the Gastrointestinal Symptom Rating Scale (GSRS- IBS). The quality of sleep was estimated by Insomnia Severity Index (ISI). The serum serotonin and melatonin levels and 5-hydroxyindoleacetic acid (5-HIAA) and 6-sulfatoxymelatonin (aMT6s) concentration in urine were determined with ELISA method. RESULTS: Compared to control group, patients with IBS-U had a higher serum levels (201.3 ± 37.8 vs 145.4 ± 36.9 ng/ml, p < 0.001) and lower levels of melatonin (5.86 ± 1,16 vs9.11 ±2.43 pg/ml, p < 0.001). Likewise, in IBS-U patients urinary excretion of 5-HIAA was greater, while aMT6s excretion was lower. Due to the above changes cyproheptadine (6 mg daily) or melatonin (7 mg daily) was recommended to be taken. After 12 weeks of taking cyproheptadine, the IBS symptoms disappeared in 86.6% patients, and in 20.0% of those taking melatonin. Both drugs improved sleep in equal measure. CONCLUSIONS: Increased serotonin secretion may be the cause of abdominal complaints in unclassified irritable bowel syndrome, what should be considered in its treatment.

Appetite stimulants for people with cystic fibrosis.

BACKGROUND: Chronic loss of appetite in cystic fibrosis concerns both individuals and families. Appetite stimulants have been used to help cystic fibrosis patients with chronic anorexia attain optimal body mass index (BMI) and nutritional status. However, these may have adverse effects on clinical status. This is an updated version of the original review. OBJECTIVES: To systematically search for and evaluate the evidence on the beneficial effects of appetite stimulants in the management of cystic fibrosis-related anorexia and synthesise reports of any side effects. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register and online trials registries; handsearched reference lists; and contacted local and international experts to identify relevant trials. Last search of the Cystic Fibrosis Trials Register: 23 May 2022. Last search of online trial registries: 10 May 2022. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of appetite stimulants compared to placebo, control, no treatment or different appetite stimulants, or to the same appetite stimulants at different doses or regimens for at least one month in adults and children with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Review authors independently extracted data and assessed risk of bias of the included trials. We used the GRADE approach to assess the certainty of the evidence and performed meta-analyses. MAIN RESULTS: We included four trials (70 participants) comparing appetite stimulants (cyproheptadine hydrochloride and megestrol acetate) to placebo; the numbers of adults or children within each trial were not always reported. We assessed the certainty of evidence as low due to the small number of participants, incomplete or selective outcome reporting, and unclear risk of selection bias.  Regarding our primary outcomes, a meta-analysis of two trials (42 participants) showed that appetite stimulants may produce a larger increase in weight (kg) at three months (mean difference (MD) 1.25 kg, 95% confidence interval (Cl) 0.45 to 2.05), and one trial (17 participants) showed a similar result at six months (MD 3.80 kg, 95% CI 1.27 to 6.33) (both low-certainty evidence). Results also showed that weight z score may increase with appetite stimulants compared to placebo at three months (MD 0.61, 95% CI 0.29 to 0.93; 3 studies; 40 participants; P < 0.001) and at six months (MD 0.74, 95% CI 0.26 to 1.22; 1 trial; 17 participants). There was no evidence of a difference in effect between cyproheptadine hydrochloride and megestrol acetate for either outcome.   Only one trial (25 participants) reported analysable data for body composition (BMI), with results favouring cyproheptadine hydrochloride compared to placebo; a further trial (16 participants) narratively agreed with this result. All four trials reported on lung function at durations ranging from two to nine months. Considering analysable data, two trials (42 participants) found that appetite stimulants may make little or no difference in forced expiratory volume at one second (FEV1) % predicted at three months, and one trial (17 participants) found similar results at six months. Two further three-month trials narratively agreed with these results. Limited information was reported for secondary outcomes. Two trials (23 participants) reported results showing that appetite stimulants may increase appetite compared to placebo at three months (odds ratio 45.25, 95% CI 3.57 to 573.33; low-certainty evidence).  Only one study reported on quality of life, finding that cyproheptadine reduced fatigue in two participants compared with none with placebo. One study (25 participants) found no difference in energy intake between appetite stimulant or placebo at three months. Insufficient reporting of adverse effects prevented a full determination of their impact. Two studies (33 participants) narratively reported similar requirements for additional antibiotics between appetite stimulants and placebo at three months.  AUTHORS' CONCLUSIONS: At six months in adults and children, appetite stimulants improved only two of the outcomes of this review: weight (or weight z score) and subjectively reported appetite. Insufficient reporting of side effects prevented a full determination of their impact. Whilst the data may suggest the potential use of appetite stimulants in treating anorexia in adults and children with cystic fibrosis, this is based upon low-certainty evidence from a small number of trials, therefore firm conclusions cannot be drawn. Clinicians need to be aware of the potential adverse effects of appetite stimulants and actively monitor any individuals prescribed these medications accordingly. Research is required to determine meaningful surrogate measures for appetite and to define what constitutes quality weight gain. Future trials of appetite stimulants should use a validated measure of symptoms including a disease-specific instrument for measuring poor appetite. This review highlights the need for multicentred, adequately powered, and well-designed trials to evaluate agents to safely increase appetite in people with cystic fibrosis and to establish the optimal mode of treatment.

Efficacy of cationic amphiphilic antihistamines on outcomes of patients treated with immune checkpoint inhibitors.

BACKGROUND: Cationic amphiphilic antihistamines have been shown to improve patient outcomes in immunogenic tumours, but whether they can augment and improve response to immunotherapy is unknown. We aim to evaluate the effect of cationic amphiphilic antihistamines in patients receiving immune checkpoint inhibitors (ICIs). METHODS: We conducted a retrospective propensity score-matched cohort study at two tertiary referral centres in Taiwan between January 2015 and December 2021. Patients who received desloratadine, cyproheptadine, and ebastine were classified as cationic amphiphilic antihistamine users. The primary outcome was overall survival, and the secondary outcomes were progression-free survival and clinical benefit rate. Patients treated with cationic amphiphilic antihistamines were matched to patients who received non-cationic amphiphilic antihistamines based on variables including age, cancer type, stage, and history of allergic diseases. RESULTS: A total of 734 ICI-treated patients were included. After matching, 68 cationic amphiphilic antihistamine and non-cationic amphiphilic antihistamine users remained for analysis. Compared with non-cationic amphiphilic antihistamine users, patients who received cationic amphiphilic antihistamines had a significantly longer median overall survival (24.8 versus 10.4 months; Log-rank, p = 0.018) and progression-free survival (10.6 versus 4.93 months; Log-rank, p = 0.004). The use of cationic amphiphilic antihistamines was associated with an approximately 50% lower risk of all-cause mortality (HR, 0.55 [95% CI: 0.34-0.91]). Survival benefits were not seen in patients who received cationic amphiphilic antihistamines before immune checkpoint blockade. These survival benefits were observed regardless of the generation of cationic amphiphilic antihistamines. CONCLUSION: The use of cationic amphiphilic antihistamines was associated with improved survival among patients treated with immunotherapy.

Effects of Cyproheptadine on Mitral Valve Remodeling and Regurgitation After Myocardial Infarction.

BACKGROUND: Ischemic mitral regurgitation (MR) is primarily caused by left ventricle deformation, but leaflet thickening with fibrotic changes are also observed in the valve. Increased levels of 5-hydroxytryptamine (5-HT; ie, serotonin) are described after myocardial infarction (MI); 5-HT can induce valve fibrosis through the 5-HT type 2B receptor (5-HT2BR). OBJECTIVES: This study aims to test the hypothesis that post-MI treatment with cyproheptadine (5-HT2BR antagonist) can prevent ischemic MR by reducing the effect of serotonin on mitral biology. METHODS: Thirty-six sheep were divided into 2 groups: inferior MI and inferior MI treated with cyproheptadine (0.5 mg/kg/d). Animals were followed for 90 days. Blood 5-HT, infarct size, left ventricular volume and function, MR fraction and mitral leaflet size were assessed. In a complementary in vitro study, valvular interstitial cells were exposed to pre-MI and post-MI serum collected from the experimental animals. RESULTS: Increased 5-HT levels were observed after MI in nontreated animals, but not in the group treated with cyproheptadine. Infarct size was similar in both groups (11 ± 3 g vs 9 ± 5 g; P = 0.414). At 90 days, MR fraction was 16% ± 7% in the MI group vs 2% ± 6% in the cyproheptadine group (P = 0.0001). The increase in leaflet size following MI was larger in the cyproheptadine group (+40% ± 9% vs +22% ± 12%; P = 0.001). Mitral interstitial cells overexpressed extracellular matrix genes when treated with post-MI serum, but not when exposed to post-MI serum collected from treated animals. CONCLUSIONS: Cyproheptadine given after inferior MI reduces post-MI 5-HT levels, prevents valvular fibrotic remodeling, is associated with larger increase in mitral valve size and less MR.

Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial.

BACKGROUND: Rupatadine was previously shown to reduce endothelial dysfunction in vitro, reduced vascular leak in dengue mouse models and to reduce the extent of pleural effusions and thrombocytopenia in patients with acute dengue. Therefore, we sought to determine the efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever (DHF) in patients with acute dengue. METHODS AND FINDINGS: A phase 2, randomised, double blind, placebo controlled clinical trial was carried out in patients with acute dengue in Sri Lanka in an outpatient setting. Patients with ≤3 days since the onset of illness were either recruited to the treatment arm of oral rupatadine 40mg for 5 days (n = 123) or the placebo arm (n = 126). Clinical and laboratory features were measured daily to assess development of DHF and other complications. 12 (9.7%) patients developed DHF in the treatment arm compared to 22 (17.5%) who were on the placebo although this was not significant (p = 0.09, relative risk 0.68, 95% CI 0.41 to 1.08). Rupatadine also significantly reduced (p = 0.01) the proportion of patients with platelet counts <50,000 cells/mm3 and significantly reduced (p = 0.04) persisting vomiting, headache and hepatic tenderness (p<0.0001) in patients. There was a significant difference in the duration of illness (p = 0.0002) although the proportion of individuals who required hospital admission in both treatment arms. Only 2 patients on rupatadine and 3 patients on the placebo developed shock, while bleeding manifestations were seen in 6 patients on rupatadine and 7 patients on the placebo. CONCLUSIONS: Rupatadine appeared to be safe and well tolerated and showed a trend towards a reducing proportion of patients with acute dengue who developed DHF. Its usefulness when used in combination with other treatment modalities should be explored. TRIAL REGISTRATION: International Clinical Trials Registration Platform: SLCTR/2017/024.

Therapeutic effect of rupatadine against l-arginine-induced acute pancreatitis in rats: role of inflammation.

Acute pancreatitis (AP) is an abrupt inflammatory disorder causing high morbidity and mortality. As AP is an insidious medical emergency, a curative modality is required instead of a preventive measure. Thus, we investigated the possible curative effect of rupatadine on a rat model of AP. Rupatadine is a potent histamine receptor 1 (H1R) and platelet-activating factor (PAF) blocker. We used four groups of six Wistar rats as follows: the control group received vehicle; the rupatadine control group received rupatadine as 6 mg/kg orally; the AP group received l-arginine intraperitoneally, and the treatment group received rupatadine at 1, 6, and 24 h after l-arginine injection. The levels of serum amylase, pancreatic oxidative parameters, and pancreatic cytokines were measured. PAF, histamine, and myeloperoxidase levels were determined in the pancreas. Histopathological and immunohistochemical examinations were performed to determine nuclear factor kappa-B (NF-κB) and caspase 3 expressions. Oxidative damage and severe inflammation were detected in the pancreas of the AP group. Rupatadine reduced the oxidative damage and the levels of proinflammatory cytokines, PAF, histamine, myeloperoxidase, NF-κB, and caspase 3 expressions. It restored the pancreatic acini to almost normal condition. Rupatadine induced important anti-inflammatory and antiapoptotic effects against l-arginine-induced AP.

Cyproheptadine: a psychopharmacological treasure trove?

Cyproheptadine has a unique pharmacologic portfolio that speaks to the idea of a pluripotent molecule beyond an antiallergic agent which can expand its therapeutic potential to address a multitude of psychiatric indications. Here, authors touch on the topic with focused literature review of extant evidence.

Comparative study evaluating antihistamine versus leukotriene receptor antagonist as adjuvant therapy for rheumatoid arthritis.

PURPOSE: Investigating the efficacy and safety of rupatadine (RUP) versus montelukast (MON) as adjuvant therapy for patients with rheumatoid arthritis (RA). METHODS: From December 2018 to December 2019, 75 patients with active RA were enrolled in this randomized double-blind placebo-controlled study. The patients were randomized into three groups (n = 25 in each group); methotrexate (MTX) group which received MTX 15-25 mg/week plus placebo tablet once daily; MTX/RUP group which received MTX plus RUP 10 mg once daily; and MTX/MON group which received MTX plus MON 10 mg once daily. The treatment duration was 3 months. At baseline and 3 months after treatment, blood samples were collected for the biochemical analysis of high-sensitivity C-reactive protein (hs-CRP), interleukins 8 and 17 (IL-8, IL-17), E-selectin, and clusterin (CLU) levels. Clinical and functional assessments using Disease Activity Score-CRP (DAS28-CRP) and Multidimensional Health Assessment Questionnaire (MDHAQ) were performed. RESULTS: Both RUP and MON produced clinical and functional improvements which were translated by significant improvements in DAS28-CRP score and MDHAQ. Rupatadine significantly reduced all measured parameters (P < 0.05) except for IL-17 and CLU. Montelukast significantly decreased all measured variables (P < 0.05) except for E-selectin. Interleukin-8 was positively correlated with IL-17 and CLU, while hs-CRP was positively correlated with E-selectin and body mass index (BMI). Both drugs were well tolerated; somnolence was the common side effect for RUP. No neuropsychiatric events were reported with MON. CONCLUSION: Rupatadine or montelukast may serve as a potential adjuvant therapy for patients with rheumatoid arthritis secondary to the preliminary evidence of efficacy and safety. ClinicalTrials.gov identifier NCT03770923, December 10, 2018.

Cyproheptadine as an appetite stimulant in children with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multi-organ genetically inherited disease that leads to progressive lung disease and nutrient malabsorption. The aim of this study was to assess the effectiveness of cyproheptadine (CH) (Periactin®) as an appetite stimulant on improving the nutrition status of paediatric patients with CF. METHODS: We conducted a retrospective study of 15 patients with a suboptimal nutrition status prescribed CH for ≥12 months from 2013 to 2018. Change in Body Mass Index (BMI) z-score and lung function before vs. after treatment with CH were measured as well as dose-response relationship. RESULTS: The mean change in BMI z-score over 12 months of treatment with CH was +0.91 compared to -0.52 in the previous 12 months (p∗∗∗ = 0.0002). There was also a trend towards an improvement in lung function over the 12 months of CH treatment compared to the 12 months prior (+2.79 vs -6.2% (p = 0.07)). No dose-response relationship was observed. CONCLUSION: These results suggest that CH is effective at improving the nutrition status of paediatric CF patients with suboptimal nutrition.

The clinical evidence of second-generation H1-antihistamines in the treatment of allergic rhinitis and urticaria in children over 2 years with a special focus on rupatadine.

INTRODUCTION: Many obstacles limit the development of pharmacologic studies in children, in particular ethical and practical issues. Therefore, although second-generation H1-antihistamines (sgAH) are recommended by international guidelines as first-line therapy in childhood allergies, most data on the efficacy of antihistamines in children has been extrapolated from studies in adult patients. AREAS COVERED: The current review focuses on rupatadine, a well-studied modern sgAH that has dual affinity for histamine H1-receptors and PAF receptors. In recent years, clinical efficacy and safety controlled-clinical trials on rupatadine were conducted in children and were based on latest current guidelines using validated tools of allergic rhinitis and urticaria. EXPERT OPINION: Children are not little adults since they present specific physiologic, metabolic, and developmental differences that should be evaluated in specific trials. The clinical evidence with rupatadine in children is the most recent and validated in accordance with current recommendations, with extensive direct data on efficacy and safety in pediatric populations over 2 years old.

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.

Two Cases of Serotonin Syndrome After Bupropion Overdose Treated With Cyproheptadine.

BACKGROUND: Bupropion is not known to have direct serotonin agonism or inhibit serotonin reuptake. In spite of this, it has been implicated as a causative agent of serotonin syndrome. We highlight two cases of single-agent bupropion overdose that subsequently met the diagnosis of serotonin syndrome by the Hunter criteria, despite the absence of direct serotonergic agents. CASE 1: A 14-year-old boy intentionally ingested an estimated 30 bupropion 75-mg immediate-release tablets. He presented in status epilepticus, was intubated, and was placed on midazolam and fentanyl infusions. He developed tremor, ankle clonus, and agitation. He was administered cyproheptadine for presumed serotonin syndrome with temporal improvement in his symptoms. CASE 2: A 19-year-old woman intentionally ingested an estimated 53 bupropion 150-mg extended-release tablets. She had a seizure and required sedation and intubation. During her course, she developed hyperthermia, inducible clonus, and hyperreflexia. She was treated with cyproheptadine without temporal improvement of symptoms but improved the following day. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although bupropion is not known to be directly serotonergic, it has been implicated as the single causative agent after overdose. This may be due to an indirect increase in activity of serotonergic cells. In these cases, bupropion overdose resulted in a clinical presentation consistent with serotonin syndrome, with the first having a temporal improvement after treatment with cyproheptadine. Physicians need to be aware of the potential serotonergic activity of bupropion for accurate assessment and treatment of this dangerous condition.

COVID-19, microthromboses, inflammation, and platelet activating factor.

Recent articles report elevated markers of coagulation, endothelial injury, and microthromboses in lungs from deceased COVID-19 patients. However, there has been no discussion of what may induce intravascular coagulation. Platelets are critical in the formation of thrombi and their most potent trigger is platelet activating factor (PAF), first characterized by Demopoulos and colleagues in 1979. PAF is produced by cells involved in host defense and its biological actions bear similarities with COVID-19 disease manifestations. PAF can also stimulate perivascular mast cell activation, leading to inflammation implicated in severe acute respiratory syndrome (SARS). Mast cells are plentiful in the lungs and are a rich source of PAF and of inflammatory cytokines, such as IL-1ß and IL-6, which may contribute to COVID-19 and especially SARS. The histamine-1 receptor antagonist rupatadine was developed to have anti-PAF activity, and also inhibits activation of human mast cells in response to PAF. Rupatadine could be repurposed for COVID-19 prophylaxis alone or together with other PAF-inhibitors of natural origin such as the flavonoids quercetin and luteolin, which have antiviral, anti-inflammatory, and anti-PAF actions.

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.