Recently, abuse and fatal overdoses of over-the-counter (OTC) medications have become serious social and health issues worldwide. However, many drug components in OTC medications that are abused have different chemical structures from those assessed by commercially available rapid drug test kits. In this research, we focused on using dried blood spot (DBS) samples to develop a simple and accurate method for forensic toxicological analysis of drugs of interest in deaths by poisoning. We combined the DBS method with liquid chromatography coupled with electrospray ionization-tandem mass spectrometry to quantify eight OTC drug components (apronal, caffeine, chlorpheniramine, dextromethorphan, diphenhydramine, diprophylline, noscapine, and promethazine). The linearities of the calibration curves were good in the concentration range of 0.1-2.0 μg/mL. The method achieved repeatable and accurate quantification of the eight target drugs with intra- and inter-assay coefficients of variation of below 13.0% and 12.6%, respectively. Comparison with our general practice method showed good positive correlations at the quantifiable concentrations of all drugs. Furthermore, when applied to an actual case, it was possible to diagnose death by drug poisoning, confirming the usefulness of this method.

Bupropion hydrochloride is an antidepressant drug belonging to the aminoketone class first introduced in 1985. It is currently FDA-approved for treating major depressive disorder, seasonal affective disorder, and smoking cessation with several off-label uses, including sexual dysfunction secondary to antidepressant use, generalized anxiety disorder, ADHD, and bipolar disorder. Multiple formulations exist, including immediate-release (IR), sustained-release (SR), and extended-release (XL).[1] Adverse drug effects with therapeutic dosing are nonspecific and may include dry mouth, constipation, headache, nausea, agitation, insomnia, and weight loss. Bupropion was withdrawn in 1986 after new-onset seizures were reported in a small portion of bulimic patients; however, it was reintroduced in 1989 at lower dose ranges. The drug is now contraindicated in patients with seizure history, eating disorders, or those undergoing ethanol or CNS depressant withdrawal. The risk of seizures with daily doses below 300 mg is estimated at 0.1% but increases to 0.4% with doses up to 450 mg daily.[1] Overdose is frequently associated with seizures, tachycardia, and agitation.[1] The extended-release formulation has also been associated with delayed seizures for up to 24 hours after ingestion.[2] Status epilepticus, life-threatening arrhythmias, and cardiogenic shock have all been reported in overdose.

The increasing non-medical use of dextromethorphan (DM), particularly among adolescents, has raised concerns regarding its potential neurobiological consequences. However, the precise mechanisms underlying its neurotoxicity, particularly the involvement of the gut microbiota, remain unclear. A novel probiotic strain, Bacillus aerolatus CX253, has demonstrated the capacity to regulate gut microbial homeostasis and attenuate inflammatory responses, yet whether it can mitigate DM-induced neurotoxicity remains unknown. In the present study, a subchronic dose-escalation DM exposure model was established in mice. Through behavioral assessments, 16S rRNA sequencing, short-chain fatty acid (SCFA) analysis, and molecular-level investigations, we systematically evaluated the neurobehavioral effects of DM and the prophylactic efficacy of CX253. The results showed that DM exposure significantly altered gut microbial composition, characterized by increased abundance of Akkermansia and Desulfovibrionaceae and decreased abundance of Muribaculaceae. These alterations were accompanied by reduced fecal butyrate levels, impaired intestinal barrier function, and elevated circulating lipopolysaccharide (LPS) and inflammatory cytokines. At the central level, DM exposure led to upregulation of pro-inflammatory cytokines in the hippocampus, glial activation, and marked suppression of the pro-survival Apelin-PI3K/Akt/mTOR signaling pathway, ultimately manifesting as increased anxiety-like behaviors and impaired spatial memory. Prophylactic administration of CX253 preserved gut microbial diversity, enriched beneficial taxa including Bifidobacteriaceae, Bacteroides, and Lachnospiraceae_NK4A136_group, increased fecal butyrate levels, alleviated intestinal barrier dysfunction as well as peripheral and central inflammatory responses, and specifically restored the DM-suppressed Apelin-PI3K/Akt/mTOR pro-survival signaling pathway, thereby improving neurobehavioral performance. Correlation and mediation analyses further suggested that these protective effects were closely associated with elevated butyrate levels. Collectively, these findings not only expand the current understanding of the mechanisms underlying DM-induced neurotoxicity but also provide a novel mechanistic framework and a translationally promising candidate strain for microbiota-based preventive strategies targeting substance misuse-related neuropsychiatric disorders.

BACKGROUND Dextromethorphan (DXM) inhibits serotonin reuptake when taken in large doses, potentially causing serotonin syndrome, which is likely life-threatening. Despite a few reports of serotonin syndrome after DXM overdose, no case report has provided a detailed analysis of serial blood DXM levels alongside the clinical course. Here, we present a case with serial measurements of blood DXM levels taken over time. CASE REPORT A 24-year-old man with bipolar disorder and attention-deficit/hyperactivity disorder, treated with trazodone and methylphenidate, ingested 300 mg of DXM (4.6 mg/kg). After 10 hours, he exhibited agitation, confusion, and impaired consciousness. On admission, his DXM blood level was 398 ng/mL; trazodone and methylphenidate levels were both <1 ng/mL. He developed serotonin syndrome with spontaneous clonus and seizures, requiring diazepam, sedation, intubation, and ventilation. By hospital day 3, the DXM level decreased to 26 ng/mL; by day 5, it was undetectable. Despite clinical stabilization and extubation by day 4, hallucinations and delusions persisted. After receiving a diagnosis of acute and transient psychotic disorder on day 9, he was transferred to the psychiatry department. With oral therapy and electroconvulsive therapy, he improved by day 33. The final diagnosis was substance/medication-induced psychotic disorder. CONCLUSIONS Our case report provides a detailed timeline of blood DXM concentrations along with the clinical course in a patient with serotonin syndrome after an acute overdose. The serial measurements support the importance of symptom-focused monitoring to guide treatment decisions.

Dextromethorphan and bupropion in combination are approved to treat major depressive disorders in adults. This case report describes a patient with a history of treatment-resistant depression who presented to the emergency department after overdosing on approximately 30 tablets of dextromethorphan-bupropion 45-105 mg in a suicide attempt. The patient required intubation, gastrointestinal decontamination, and changes in her antidepressant medications. The patient reported no suicidality by the end of her hospitalization, and she was discharged on paroxetine 40 mg daily and quetiapine 200 mg at night. Clinicians should be cautious and vigilant when prescribing or considering these medications together, particularly in populations at risk of overdose.

Dextromethorphan has antitussive effects and therefore is mainly used in over-the-counter cold remedies. However, abuse of this addictive substance as a 'recreational drug' has become problematic. We recently experienced two autopsy cases in which dextromethorphan intoxication likely contributed significantly to the cause of death. In one of these cases, the femoral vein blood concentration of dextromethorphan was in the lethal range (17.7 µg/mL), and death was considered to be solely due to poisoning with this drug. In the other case, the direct cause of death was hanging, but the dextromethorphan concentration was in the intoxication range (3.9 µg/mL), and through the associated abnormal behavior, may have contributed to the cause of death. In addition, multiple liquid and tissue samples from the autopsies of these two subjects were used to examine the distribution of dextromethorphan in the body by liquid chromatography-mass spectrometry.

Serotonin syndrome has been known as a disease with a potentially life-threatening condition and which occurs usually drug-related and results from an increase in serotonergic activity in the central nervous system. We experienced a fatal case in which may have led to the development of serotonin syndrome and death by intaking privately imported dextromethorphan and moclobemide, MAOIs. We report an autopsy case, a 44-year-old man was found deceased on the bed of his girlfriend's house by her mother. Beside the victim, there was a bottle, which was presumed to have been personally purchased on the Internet, contained two different types of tablets. There were no findings that suggested the presence of obvious trauma or internal diseases in the judicious autopsy. Additional drug testing was performed, and the concentration of dextromethorphan in heart blood was 37.2 μg/mL was detected. In addition, the fact that the patient had a high body temperature and intramuscular bleeding at the time of death strongly suggests that he had died due to serotonin syndrome. In this case, the diagnosis of serotonin syndrome was made on the basis of autopsy findings and additional drug testing. In cases of suspected death due to serotonin syndrome, additional drug testing and quantitative evaluation to identify the causative agent would be helpful in the diagnosis.

BACKGROUND Dextromethorphan is a widely used over-the-counter antitussive medication. Generally safe within the recommended dosages, its misuse can lead to severe adverse effects, particularly in large amounts. However, comprehensive descriptions of severe overdose cases - including pharmacokinetic data of dextromethorphan and its active metabolite (dextrorphan) - are scarce. CASE REPORT A 21-year-old woman with schizophrenia ingested 20 280 mg of dextromethorphan along with other prescribed medications during a suicide attempt. She was discovered semiconscious and experienced a generalized seizure en route to the hospital. Despite intensive treatments - including endotracheal intubation and administration of propofol and midazolam - she continued to experience refractory status epilepticus. Subsequent neurological examination revealed cranial nerve reflex loss. The serum concentration of dextromethorphan was 5.8 mg/L on admission and decreased to 2.2 mg/L by day 1 and 1.1 mg/L by day 2, contrasting with that of dextrorphan, which remained within the therapeutic limits. By day 4, her condition stabilized; she became alert, responsive to commands, and was successfully extubated. She was discharged on day 9 without any sequelae. CONCLUSIONS This report describes the case of a patient who survived a massive dextromethorphan overdose, who presented with refractory status epilepticus followed by reversible suppression of cranial nerve reflexes. The pharmacokinetic profiles suggested that dextromethorphan, rather than dextrorphan, was responsible for the symptoms. High-dose dextromethorphan ingestion can lead to varied and potentially fatal outcomes, especially when compounded by metabolism-altering factors such as CYP2D6 inhibition, genetic variability, or co-ingested medications. This case underscores the importance of prompt, intensive supportive care in managing severe dextromethorphan toxicity.