Chronic treatment with clomipramine, a tricyclic antidepressant drug, reduces symptoms of obsessive-compulsive disorder (OCD) and can influence the activity of the hypothalamic-pituitary-adrenal axis. However, little is known regarding the effects of acute clomipramine on the immediate expression of stress responses. Serotonergic drugs can elicit surfacing, a behavioral profile potentially related to toxicity in fish, although surfacing has not yet been observed after clomipramine exposure. The present study investigated the impact of acute exposure to clomipramine on basal and stress-induced behaviors in the novel tank test and cortisol levels in mixed-sex, wild-type, adult zebrafish (Danio rerio). The findings show clomipramine-exposed groups (regardless of stress exposure) spent much more time in the top of the novel tank and had significantly less overall motor activity in the behavioral task compared to the fish not exposed to the drug. Then, the dose-dependent effects of acute clomipramine on activity in the surface of the novel tank (top third of the top half) were investigated further. Clomipramine dose-dependently increased surface-dwelling and elicited a dose-dependent hypoactivity in overall motor behavior. There were no statistically significant differences in whole-body cortisol levels in either experiment. Like other serotonin-acting drugs, clomipramine strongly elicited surface-dwelling and depressed motor behavior in adult zebrafish. Additional testing is needed to elucidate whether surfacing represents a toxic state and how serotonin regulates surfacing.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a complication of systemic lupus erythematosus with diverse clinical presentations sharing common features with variable neurologic disorders. Magnetic resonance imaging (MRI) may provide imaging evidence of structural brain abnormalities associated with symptoms of NPSLE. Serotonin syndrome is a toxidrome characterized by altered mental status, autonomic hyperactivity, and neuromuscular abnormalities. It is mostly caused by medications that increase serotonin and is rarely reported as a manifestation of neuropsychiatric lupus. We presented the case of a 24-year-old Taiwanese woman with a history of systemic lupus erythematosus diagnosed at 21 years of age. The initial clinical and laboratory presentations upon diagnosis included fever, arthritis, hypocomplementemia, positive antinuclear antibody, anti-double-stranded DNA antibody, and anti-ribosomal P antibody. Her condition once remained stable under oral glucocorticoids and immunosuppressants, but she developed sudden-onset consciousness disturbance, incoherent speech, and unsteady gait ten days before our assessment. A high fever of up to 39 °C with tremor and clonus occurred at the intensive care unit. Brain MRI revealed symmetric T2 hyperintensity without diffusion restriction over the bilateral globus pallidus. High-dose pulse glucocorticoid and rituximab were prescribed during her admission and the neuropsychiatric symptoms diminished upon treatment. No alternation in mental status or involuntary movements were noted at follow-up. Our patient was diagnosed with neuropsychiatric lupus, with clinical symptoms and image findings mimicking those of serotonin syndrome. Neuroimaging, such as MRI, detects various structural brain abnormalities and may provide pathophysiological evidence of clinical manifestations.

Serotonin syndrome (toxicity), resulting from an excessive accumulation of serotonin in the central nervous system, it can occur due to various factors such as the initiation of medication, overdose or drug interactions. Diagnosing serotonin toxicity presents challenges as there are no definitive criteria. This review delves into the pathophysiology, incidence, clinical assessment and management of serotonin toxicity, stressing the significance of promptly recognizing and managing severe cases. Diagnosis relies primarily relies on clinical assessment due to the absence of specific laboratory tests. The Hunter Serotonin Toxicity criteria are commonly utilized but have only been validated in the overdose setting. Assessing the severity of toxicity is crucial for guiding management decisions. Supportive care, discontinuation of causative agents and symptomatic treatment are prioritized in management. Mild toxicity often requires withdrawal or reduction of the serotonergic agent, while more severe toxicity requires more aggressive resuscitative and supportive care. Severe serotonin toxicity characterized by hyperthermia and rigidity requires aggressive supportive measures, including benzodiazepines, intubation, paralysis and active cooling. Animal studies suggest potential benefits of 5-HT2A receptor antagonists in preventing hyperthermia and fatalities, but only at high doses. Their clinical effectiveness remains uncertain, and evidence is predominately from case series and case reports. Although commonly used, serotonin antagonists like cyproheptadine lack conclusive evidence of efficacy. Other serotonin antagonists such as chlorpromazine and olanzapine have been explored but evidence is limited to case reports. Hence, the cornerstone of treating severe cases does not lie in \'antidote\' administration or even diagnosis but in effective early resuscitative and supportive care.

UNASSIGNED: Serotonin syndrome is characterized by mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. This syndrome results from various medications that engender serotonergic overactivity. Atomoxetine is a norepinephrine reuptake inhibitor used for the treatment of attention-deficit hyperactivity disorder (ADHD). Two case reports have described serotonin syndrome induced by the combination of atomoxetine with venlafaxine or methylphenidate, but no report describes this syndrome induced by atomoxetine alone. This report describes serotonin syndrome induced solely by an overdose of atomoxetine in a patient with ADHD.
UNASSIGNED: The patient in this case was a 21-year-old man who had been treated with atomoxetine for ADHD. He was transported to our hospital 1 h after intentional ingestion of 1200 mg of atomoxetine in a suicide attempt. On admission, he showed profuse diaphoresis, marked agitation, somnolence, slight fever, tachycardia, prolonged QT interval, myoclonus, tremor, and hyperreflexia. He was diagnosed as having serotonin syndrome and was treated with administration of activated charcoal and massive infusion. Three days later, his serotonin syndrome symptoms had disappeared completely.
UNASSIGNED: Findings in this case suggest that atomoxetine alone can cause serotonin syndrome presumably via its effects of serotonin reuptake inhibition. Clinicians should consider this syndrome induced by atomoxetine overdose.

Serotonin syndrome (SS) is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system. Although more than seven decades have passed since the first description of SS, it is still an enigma in terms of terminology, clinical features, etiology, pathophysiology, diagnostic criteria, and therapeutic measures. The majority of SS cases have previously been reported by toxicology or psychiatry centers, particularly in people with mental illness. However, serotonergic medications are used for a variety of conditions other than mental illness. Serotonergic properties have been discovered in several new drugs, including over-the-counter medications. These days, cases are reported in non-toxicology centers, such as perioperative settings, neurology clinics, cardiology settings, gynecology settings, and pediatric clinics. Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers. Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings. Patients may develop SS at therapeutic dosages. Moreover, these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons. Thus, the clinical presentation (onset, severity, and clinical features) in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings. They produce considerable diversity in many aspects of SS. However, other experts discount these new developments in SS. Since SS is a potentially lethal illness, consensus is required on several concerns related to SS.

BACKGROUND: Serotonin syndrome is a potentially life-threatening condition that can occur as a result of the therapeutic use of serotonergic medications or drug interaction. In this study, we describe two cases of serotonin syndrome-associated hypertensive crisis following linezolid use.
METHODS: The first patient was a 52-year-old female who was admitted due to a diabetic foot infection and pneumonia associated with a decreased consciousness level. Serotonin syndrome occurred 24 hours after starting the linezolid use. Resistant hypertension was the main hemodynamic finding. It could not be controlled with amlodipine, valsartan, prazosin, and nitroglycerin infusion. Resistant hypertension and other symptoms of serotonin syndrome were resolved about 48 hours after discontinuation of linezolid use. The second case was a man with a history of kidney transplant, diabetes, and hypertension. He was admitted to the ICU due to severe COVID-19 broad-spectrum antibiotics [linezolid, cefepime], and remdesivir was initiated. Following intubation, continuous infusion of fentanyl was used for sedation. Within 24 hours after fentanyl and linezolid initiation, severe agitation, eye clonus, hyperreflexia, hypertension [160-186 /90-110 mmHg], and tachycardia [>100/min] were noted. With the possible diagnosis of serotonin syndrome, fentanyl was discontinued, and morphine was initiated. The patient\'s symptoms improved 48 hours after discontinuation of fentanyl.
CONCLUSIONS: Both of the patients had a history of controlled hypertension. However, serotonin syndrome occurred following the use of linezolid and concomitant/recent use of serotonergic agents. A thorough evaluation of the patient\'s medical history and current situation can help clinicians prevent this syndrome in critically ill patients.

Serotonin syndrome (SS) is a life-threatening condition caused by serotonergic medications. We describe a unique case of SS likely caused by prolonged exposure to propofol and remifentanil alone. A young male presented for vestibular schwannoma resection. Several hours into the case, the patient demonstrated hyperthermia and hemodynamic instability, followed by clonus, rigidity, shivering, and tachycardia after emergence. SS was diagnosed using Hunter\'s criteria and improved with supportive measures. While the patient endorsed a history of methamphetamine use, his urine drug screen was negative. The possibility of SS should be considered when administering propofol and remifentanil, particularly with prolonged infusions.

BACKGROUND: Malignant hyperthermia is a potentially lethal condition triggered by specific anesthetic drugs, especially a depolarizing muscle relaxant of succinylcholine (Suxamethonium). Despite the frequent use of succinylcholine with electroconvulsive therapy (ECT), there has been no reported case of potentially lethal malignant hyperthermia following ECT. In addition, the time interval between the administration of succinylcholine and the onset of malignant hyperthermia has not been outlined in the context of ECT.
METHODS: We present the case of a 79-year-old woman suffering from severe depression, who experienced severe malignant hyperthermia due to succinylcholine administration during an ECT session. She presented with a high fever of 40.2 °C, tachycardia of 140/min, hypertension with a blood pressure exceeding 200 mmHg, significant muscle rigidity, and impaired consciousness. These symptoms emerged two hours after ECT, which occurred in a psychiatric ward rather than an operating room, and reached their peak in less than 24 h. She was given 60 mg of dantrolene, which quickly reduced the muscular rigidity. Subsequently, she received two additional doses of 20 mg and 60 mg of dantrolene, which brought her fever down to 36.2 °C and completely eased her muscle rigidity within two days after ECT.
CONCLUSIONS: This is the first reported case of potentially lethal malignant hyperthermia after ECT. In addition, it highlights the delayed onset of malignant hyperthermia following an ECT procedure, emphasizing the necessity for psychiatrists to recognize its onset even after the treatment. In the light of potentially lethal consequences of malignant hyperthermia, it is critically important for psychiatrists to closely monitor both intraoperative and postoperative patient\'s vital signs and characteristic physical presentations, promptly identify any symptomatic emergence, and treat it immediately with dantrolene.

UNASSIGNED: Serotonin syndrome (SS) is an iatrogenic life-threatening condition caused by serotonergic agents. The treatment for SS involves the administration of a serotonin antagonist (cyproheptadine). However, the dosing schedule for cyproheptadine is not uniform in the literature.
UNASSIGNED: We retrospectively evaluated 23 adult patients (>18 years) admitted to the Neurology Department and met the Hunter criteria for SS.
UNASSIGNED: The mean age was 35.2 years, and 52% were female. Ten patients were managed in the intensive care unit (ICU), whereas thirteen patients were admitted to the ward. Hyperreflexia was the most common clinical feature (100%), followed by clonus (91%), tachycardia (83%), and tremor (83%). Other common clinical features were rigidity (65%), increased bowel sound (61%), diaphoresis (48%), fever (43%), hypertension (39%), and myoclonus (30%). All but one patient received two or more serotonergic drugs. Tramadol was the most common serotonergic agent (39%), followed by sodium valproate (21%), and amitriptyline (21%). Cyproheptadine was administered to all patients. All patients admitted in the ICU received a loading dose of 12 mg followed by 2 mg every 2 h for at least 24 h. All patients admitted to the ward were given 4 mg of cyproheptadine three times each day. Every patient showed at least some response to cyproheptadine within 24 h. The total doses of cyproheptadine and the length of treatment differed between patients.
UNASSIGNED: Any response to cyproheptadine at a therapeutic dose within 24 h, even a partial one, could be a diagnostic indicator of the existence of SS.

OBJECTIVE: This study aimed to analyze and map scientific literature on Neuroleptic Malignant Syndrome (NMS) and Serotonin Syndrome (SS) from prestigious, internationally indexed journals. The objective was to identify key topics, impactful articles, prominent journals, research output, growth patterns, hotspots, and leading countries in the field, providing valuable insights for scholars, medical students, and international funding agencies.
METHODS: A systematic search strategy was implemented in the PubMed MeSH database using specific keywords for NMS and SS. The search was conducted in the Scopus database, renowned for its extensive coverage of scholarly publications. Inclusion criteria comprised articles published from 1950 to December 31st, 2022, restricted to journal research and review articles written in English. Data were analyzed using Microsoft Excel for descriptive analysis, and VOSviewer was employed for bibliometric mapping.
RESULTS: The search yielded 1150 articles on NMS and 587 on SS, with the majority being case reports. Growth patterns revealed a surge in NMS research between 1981 and 1991, while SS research increased notably between 1993 and 1997. Active countries and journals differed between NMS and SS, with psychiatry journals predominating for NMS and pharmacology/toxicology journals for SS. Authorship analysis indicated higher multi-authored articles for NMS. Top impactful articles focused on review articles and pathogenic mechanisms. Research hotspots included antipsychotics and catatonia for NMS, while SS highlighted drug interactions and specific medications like linezolid and tramadol.
CONCLUSIONS: NMS and SS represent rare but life-threatening conditions, requiring detailed clinical and scientific understanding. Differential diagnosis and management necessitate caution in prescribing medications affecting central serotonin or dopamine systems, with awareness of potential drug interactions. International diagnostic tools and genetic screening tests may aid in safe diagnosis and prevention. Reporting rare cases and utilizing bibliometric analysis enhance knowledge dissemination and research exploration in the field of rare drug-induced medical conditions.