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Dextromethorphan is a centrally acting, nonopioid antitussive widely used for cough suppression and increasingly recognized for its therapeutic potential in neuropsychiatric care. Commonly found in over-the-counter cough and cold products, it has multiple central nervous system effects, including N-methyl-D-aspartate receptor antagonism and sigma-1 receptor agonism. These properties support its FDA-approved use for pseudobulbar affect when combined with quinidine and for major depressive disorder when combined with bupropion, highlighting the importance of understanding its mechanisms and clinical applications. This activity provides a focused review of dextromethorphan, covering pharmacology, pharmacokinetics, therapeutic indications, and key safety considerations. The activity also reviews factors affecting metabolism, including cytochrome P450 2D6 variability, clinically relevant drug interactions, and the risk of serotonin syndrome, offering guidance for safe and effective clinical use. Additionally, recognition and management of misuse and overdose are addressed, including common clinical presentations and recommended interventions. By examining these aspects, healthcare professionals are equipped with the knowledge needed to optimize patient care and ensure the responsible use of dextromethorphan in both cough management and emerging neuropsychiatric therapies. Objectives: Apply evidence-based indications for dextromethorphan in cough suppression, pseudobulbar affect, and major depressive disorder. Assess patients for risk factors related to serotonin syndrome, drug interactions, and metabolic variability. Differentiate normal and abnormal responses to dextromethorphan therapy, including expected therapeutic effects versus adverse reactions. Strategize with the interprofessional healthcare team to develop protocols for early recognition, management, and follow-up of dextromethorphan-related adverse events. Access free multiple choice questions on this topic.

Signs and Symptoms of Overdose One significant concern regarding dextromethorphan toxicity is its OTC misuse, which has steadily increased since the early 2000s. This misuse is referred to by slang terms such as "going pharming," "robotripping," and "dexing." In 2006, three specific OTC product formulations accounted for 66% of reported dextromethorphan misuse cases in the United States, with Coricidin HBP Cough & Cold Tablets and Robitussin products being prominent. A life-threatening toxicity associated with dextromethorphan abuse is serotonin syndrome, resulting from its serotonin reuptake inhibition properties. When combined with SSRIs or MAOIs, the risk of serotonin syndrome increases significantly. Symptoms include agitation, confusion, dilated pupils, headache, tachycardia, hypotension, high fever, seizures, irregular heartbeat, and may progress to unconsciousness.[43][44][45] Despite the rise in misuse, public health efforts and legislative actions restricting the sale of dextromethorphan-containing products to minors have helped stabilize or reduce abuse rates in recent years. However, continued vigilance is essential to prevent misuse and associated toxicities, given dextromethorphan's widespread availability and potential for harm. These trends underscore the importance of monitoring and educating patients on the proper use of dextromethorphan-containing medications. Management of Overdose Once airway, breathing, and circulation are stabilized, management of dextromethorphan poisoning focuses on identifying and treating its major complications: agitation/psychosis, hyperthermia, rhabdomyolysis, serotonin syndrome, and seizures. Agitation and psychotic symptoms should be managed with benzodiazepines such as lorazepam, which also decrease muscle activity and lower the risk of progression to hyperthermia or seizures. Antipsychotic agents should be avoided because they may worsen anticholinergic effects and impair thermoregulation.

Once airway, breathing, and circulation are stabilized, management of dextromethorphan poisoning focuses on identifying and treating its major complications: agitation/psychosis, hyperthermia, rhabdomyolysis, serotonin syndrome, and seizures. Agitation and psychotic symptoms should be managed with benzodiazepines such as lorazepam, which also decrease muscle activity and lower the risk of progression to hyperthermia or seizures. Antipsychotic agents should be avoided because they may worsen anticholinergic effects and impair thermoregulation. Hyperthermia is treated with active evaporative cooling rather than antipyretics, and patients with core temperatures greater than or equal to 40 °C may require neuromuscular paralysis and endotracheal intubation to halt heat production. Rhabdomyolysis is managed with aggressive isotonic intravenous fluids to maintain a urine output of at least 4 mL/kg/h, with close monitoring for electrolyte abnormalities, particularly hyperkalemia. Please see StatPearls' companion resource, "Dextromethorphan Toxicity," for more information. Serotonin syndrome is treated with benzodiazepines and, when necessary, cyproheptadine.[46][47] Seizures are treated first with benzodiazepines, with phenobarbital as a second line. In cases of respiratory depression, naloxone may reverse coma or hypoventilation, particularly when there is concomitant opioid/benzodiazepine ingestion, and mechanical ventilation may be required. Coingestants commonly found in OTC preparations, such as acetaminophen or sympathomimetics, require appropriate antidotes, including N-acetylcysteine for acetaminophen toxicity. Most uncomplicated cases resolve within several hours, but severe toxicity warrants intensive care monitoring. All intentional overdoses require psychiatric assessment before discharge. For the latest recommendations, clinicians should contact the regional poison control center at 1-800-222-1222.

Dextromethorphan is one of the most widely used OTC antitussives. Pharmacists, primary care physicians, and advanced practice providers play a key role in counseling patients on appropriate dosing, potential drug-drug interactions, and the risks associated with combining dextromethorphan with serotonergic medications. In patients with chronic cough unresponsive to dextromethorphan, collaboration among pulmonologists, allergists, and gastroenterologists is essential to evaluate alternative causes such as asthma, gastroesophageal reflux disease, or upper airway cough syndrome. Since dextromethorphan became available OTC, its misuse and overdose have increased significantly.[48] Diagnosis and management of dextromethorphan overdose require an interprofessional healthcare team including clinicians, advanced practice providers, nurses, pharmacists, and any witnesses or family members. Thorough documentation of the patient's medical history and current medications is vital for identifying major overdose complications such as serotonin syndrome. Treatment for serotonin syndrome involves hydration, drug withdrawal, body temperature management, and seizure control. Without timely intervention, serotonin syndrome and dextromethorphan overdose can be fatal. Paramedics play a crucial role in gathering information from witnesses and identifying empty pill bottles at the scene. The triage nurse should consider the possibility of a drug overdose and direct patient disposition accordingly. A detailed history is essential for establishing the time of onset and for monitoring the patient's clinical progression or deterioration. Emergency department physicians are responsible for ordering relevant laboratory tests, including blood or urine drug levels, when appropriate. Consultation with pharmacists, toxicologists, radiologists, and hospitalists should be obtained as needed. Psychiatry consultation should be obtained in cases of intentional overdose. According to the American Association of Poison Control Centers, out-of-hospital management of dextromethorphan overdose includes two grades of recommendation. Grade D: This category applies to patients with suicidal ideation, intentional abuse, or malicious intent, who should be referred immediately to the nearest emergency department

According to the American Association of Poison Control Centers, out-of-hospital management of dextromethorphan overdose includes two grades of recommendation. Grade D: This category applies to patients with suicidal ideation, intentional abuse, or malicious intent, who should be referred immediately to the nearest emergency department Grade C: This category applies to patients with effects beyond mild or those following an acute ingestion, who should also be promptly referred to an emergency department. Patients who ingest 5 to 7.5 mg/kg should receive poison control center–initiated treatments, with follow-up every 2 to 4 hours. Any patient exhibiting persistent or worsening symptoms or who ingests more than 7.5 mg/kg should be referred immediately to emergency care.[49] A structured approach that emphasizes interprofessional collaboration, including physicians, advanced practice providers, pharmacists, and relevant specialists, along with timely referral, is essential for improving healthcare outcomes and reducing morbidity and mortality associated with dextromethorphan misuse and overdose.