A woman in her 90s who lived alone and had a history of unspecified dementia and pulmonary tuberculosis presented with a four-day history of lower abdominal pain. Her only regular medication was diazepam, which she dispensed from a press-through package (PTP) and had been cutting individual tablets from the sheet using scissors. Upon admission, she was hypothermic (body temperature 34°C), with otherwise preserved vital signs (blood pressure 131/65 mmHg, heart rate 79 beats/min, SpO₂ 98% on room air). She had no recollection of having swallowed a PTP. Laboratory findings showed a markedly elevated C-reactive protein level of 32.58 mg/dL, severe hypoalbuminemia (albumin 2.4 g/dL), and mild metabolic acidosis (pH 7.300, HCO₃⁻ 17.6 mmol/L) on arterial blood gas analysis. Abdominal computed tomography (CT) revealed a high-density object surrounded by a low-density halo in the ileum approximately 10 cm proximal to the ileocecal valve, along with localized free air and abscess formation in the right lower abdomen, consistent with a PTP-induced ileal perforation. Emergency laparotomy revealed a spindle-shaped ileal perforation, with an intact PTP sheet partially extruding through the defect. An abscess had formed between the abdominal wall and the bowel at the perforation site. Primary repair, omental reinforcement, and peritoneal lavage with drainage were performed without bowel resection or stoma creation. The patient recovered without complications and was discharged on postoperative day 15. This case illustrates two key points: the characteristic CT appearance of a retained PTP can confirm the diagnosis even without an ingestion history, and occult PTP ingestion should be considered in elderly patients with dementia who present with acute abdomen, irrespective of whether an ingestion history can be elicited.

This study focused on examining the anxiolytic effects of Schisandrin B (SchB) in rats exhibiting anxiety-like behaviors and investigating the mechanisms involved. Behavioral assessments were conducted using the elevated plus-maze test and the open field test. The results showed that Schisandrin B at a dose of 10 mg/kg significantly alleviated anxiety-like behaviors in rats, with an efficacy comparable to that of the positive control drug diazepam. Mechanistic studies indicate that, at the central level, Schisandrin B effectively maintains the homeostasis of the glutamatergic system in the hippocampus and the HPA axis. Specifically, Schisandrin B downregulates the stress-induced overexpression of ionotropic glutamate receptor subunits at both the mRNA and protein levels, including NMDAR subtypes (GluN1A, GluN2A, and GluN2B) and AMPAR subtypes (GluA1 and GluA2), thereby restoring the glutamate/γ-aminobutyric acid (Glu/GABA) ratio to physiological levels. In addition, Schisandrin B suppresses the hyperactivation of the HPA axis by reducing the secretion of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT). Meanwhile, it ameliorates neuronal and synaptic ultrastructural damage in the hippocampus and upregulates the expression of synaptic plasticity-related proteins, SYP and PSD-95, thereby improving synaptic transmission and function. At the peripheral intestinal level, Schisandrin B alleviated colon shortening in anxiety-model rats and reduced fecal pH, thereby improving intestinal environmental homeostasis. Schisandrin B also promoted the upregulation of tight junction proteins (ZO-1, Occludin, and Claudin-1) in the colonic tissues, contributing to the restoration of colonic mucosal integrity, attenuation of inflammatory infiltration, and reinforcement of intestinal barrier function. Collectively, Schisandrin B exerts systemic anxiolytic effects by centrally regulating hippocampal glutamatergic neurotransmission, HPA axis activity, and synaptic plasticity, while simultaneously repairing peripheral intestinal barrier dysfunction. These results indicate the potential of Schisandrin B as a therapeutic candidate for anxiety disorders.

Tizanidine, an imidazole derived α2 adrenergic agonist, is widely prescribed for spasticity and chronic musculoskeletal pain. Abrupt discontinuation can precipitate withdrawal syndromes characterized by sympathetic overactivity. Although pharmacologically plausible, this phenomenon is potentially underreported in clinical practice. We describe four patients with diverse comorbidities who developed acute tizanidine withdrawal. All cases were directly observed at a single tertiary care center and identified during routine inpatient clinical practice over a defined timeline. Case 1 was a 24 year old female admitted with empagliflozin induced diabetic ketoacidosis who experienced hypertensive crisis and tachycardia following abrupt cessation of chronic high dose tizanidine. Case 2 was a 29 year old female with Crohn's disease who developed tremors, anxiety, and autonomic instability after reducing her regimen from 40 mg nightly to 16 mg daily. She had self-discontinued her last dose prior to presentation. Case 3 was a 29 year old female with recurrent pancreatitis, resistant hypertension, and an adrenal incidentaloma who presented with severe hypertension and tremors after discontinuing both tizanidine and diazepam. Symptoms began within approximately 24 h of abrupt cessation. Case 4 was a 42 year old male with asthma, hypertension, anxiety disorder, bariatric surgery, methamphetamine use, and more than ten prior admissions specifically for tizanidine withdrawal, who presented with palpitations, tremors, vomiting, and hypertensive crisis after abrupt dose reduction. In all cases, reintroduction of tizanidine followed by a structured tapering regimen resulted in clinical stabilization. These cases highlight the clinical significance of tizanidine withdrawal, its diverse presentations, and the importance of cautious tapering. Patient education on avoiding abrupt discontinuation is essential, particularly for individuals with psychiatric comorbidities or prior withdrawal episodes. Awareness of this underrecognized syndrome is critical to prevent misdiagnosis and ensure safe prescribing practices.

Syncope in older adults is often multifactorial, with polypharmacy being a common and potentially modifiable factor. Benzodiazepines are prescribed for anxiety and insomnia in this population despite being associated with adverse effects, including falls, cognitive impairment, and hypotension. We present the case of a 68-year-old female patient with multimorbidity and recurrent unexplained syncope despite extensive cardiologic and neurologic evaluations. She was on diazepam therapy for anxiety as part of a complex medication regimen. A temporal relationship was observed between diazepam administration and episodes of hypotension, with systolic blood pressure dropping as low as 70 mmHg approximately three to four hours after dosing. Following stepwise dose reduction of diazepam, the frequency of syncopal episodes decreased over a four-month period, with no alternative single factor fully explaining the improvement. This case highlights the importance of medication review in older adults presenting with syncope. Benzodiazepines may contribute to clinically significant hypotension, particularly in the context of polypharmacy, and dose reduction or deprescribing may lead to clinical improvement.

We report on the development of a highly water-soluble pegylated imidazodiazepine ETK-II-83. The compound binds selectively to GABAA receptors among forty-five other receptors expressed in the brain with a higher affinity for the α5-containing GABAA receptors. The compound is converted in vitro by liver microsomes into ETK-III-9. The metabolic reaction selectively oxidizes the polyethylene glycol groups of ETK-II-83 forming eventually the stable 2-hydroxyethyl amide-bearing ETK-III-9. The conversion is fast with a half-life of 5.33 min. ETK-III-9 strongly binds to α3/α5 containing GABAA receptors. A pharmacokinetic study with ETK-II-83 confirmed metabolic instability resulting in low AUCs for blood and brain. Interestingly, higher brain concentrations than blood concentrations (KP = 5.17) were observed. The in vivo formation of ETK-III-9 inside ETK-II-83-treated animals was rapid and peaked at 40 min. Almost equal amounts of ETK-III-9 were found in blood and brain with half-lives of 219 and 202 min, respectively. We also conducted a pharmacokinetic study with ETK-III-9 at the same dose and observed three times higher AUCs for blood and brain. Importantly, the free brain concentration of ETK-III-9 in ETK-II-83-administrated animals was higher than its affinity for the GABAA receptors. This was confirmed by investigating ETK-II-83 with two anxiety mouse models. For the elevated plus maze, ETK-III-9- and ETK-II-83-treated animals spent significantly more time in the open arm than vehicle-treated animals, without any differences in the overall distance traveled. ETK-III-9- and ETK-II-83-treated animals also buried fewer marbles than vehicle control animals. To demonstrate that these effects were not caused by sedation or inhibition of sensorimotor inhibition, we conducted open field and rotarod tests. For both tests, ETK-III-9- and ETK-II-83-treated animals did not behave differently from vehicle-treated mice in contrast to diazepam-treated animals. The innovation is a highly water-soluble prodrug ETK-II-83 that metabolizes to ETK-III-9, an α3/α5 GABAA receptor-selective compound that reduces anxiety in rodent models.

Catatonia is a neuropsychiatric syndrome characterized by disturbances in motor activity, affect, and autonomic function. Although often associated with primary mood or psychotic disorders, it can be precipitated or sustained by systemic infections such as urinary tract infection (UTI). We describe a 60-year-old man with recurrent catatonia and diagnoses of schizophrenia, bipolar disorder, and major neurocognitive disorder, whose latest episode of catatonia, described in this case report, was preceded by psychosocial stress and appeared to be exacerbated by polymicrobial UTI, bacteremia, and urosepsis. He had a history of neuroleptic malignant syndrome (NMS) and an inconsistent response to electroconvulsive therapy (ECT), limiting usual first-line treatment options. During this admission, he developed Klebsiella pneumoniae UTI with Staphylococcus simulans bacteremia and later Pseudomonas aeruginosa urosepsis, in the context of mixed central and nephrogenic diabetes insipidus likely related to long-term lithium therapy. The patient's catatonia proved refractory to very high-dose lorazepam but improved with an intensive, multimodal regimen including intravenous (IV) benzodiazepines (diazepam, midazolam), enteral and subsequently oral lorazepam, zolpidem, memantine, and aggressive treatment of infection and electrolyte abnormalities. He ultimately regained baseline function and was discharged on a slow taper of benzodiazepines and zolpidem. This case illustrates the bidirectional relationship between infection, autonomic and immune dysregulation, and catatonia; highlights practical challenges when treatment with benzodiazepines and ECT is constrained by medical comorbidity; and supports considering adjunctive GABAergic and glutamatergic agents in carefully selected cases of refractory catatonia, under close specialist supervision.