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Objective: To report the development of morbilliform rash and serotonin toxicity after the addition of milnacipran to a patient's medication therapy., Case Summary: A 57-year-old white female presented to the emergency department because of a full-body morbilliform rash, which appeared 9 days after initiation of milnacipran 50 mg twice daily. In the emergency department the patient's vital signs were: heart rate 121 beats/min, blood pressure 180/100 mm Hg, and temperature 38.9 °C. The patient reported diarrhea, nausea, dizziness, restlessness, and increased muscle pain. Her history included recurrent breast cancer first diagnosed in 1999, hypertension, fibromyalgia, depression, osteopenia, gastroesophageal reflux disease, insomnia, and endometriosis. Her home medications included milnacipran, fluoxetine, alprazolam, zolpidem, zoledronic acid, anastrozole, doxepin, ranitidine, levocetirizine, doxazosin, tramadol, vitamin D, and ferrous gluconate. The patient's increased heart rate, blood pressure, and temperature, as well as restlessness, self-reported diarrhea and nausea, and self-reported increase in muscle pain, indicated serotonin toxicity. Milnacipran, fluoxetine, and tramadol were discontinued, while doxepin was continued. Treatment consisted of acetaminophen, diphenhydramine, methylprednisolone, promethazine, and hydralazine 10 mg intravenously. The following morning all vital signs were within normal limits and the patient's diarrhea, nausea, dizziness, restlessness, and muscle pain resolved. She was discharged the following morning. The rash had resolved after day 2 of hospital discharge, which was the fourth day after discontinuation of milnacipran., Discussion: Given the patient's symptoms, the timing of symptom onset, the patient's history, and findings on physical examination, as well as use of the Naranjo probability scale, milnacipran was deemed the probable cause of the morbilliform reaction and serotonin toxicity. Only 1 case report of rash and 2 case reports of serotonin syndrome associated with milnacipran have been reported., Conclusions: It is important to increase awareness of the possibility of developing morbilliform rash and serotonin toxicity with milnacipran therapy, as both conditions can be associated with poor outcomes if not detected early and treated appropriately.

Objective: To evaluate the use of urine dopamine and catecholamine concentrations as diagnostic aids in a patient with neuroleptic malignant syndrome (NMS) in the emergency department setting., Case Summary: A 61-year-old female on multiple medications, including several antipsychotics, rapidly deteriorated, with fever, lead-pipe rigidity, and decreased level of consciousness. The patient died 20 days after initial presentation to an emergency department. The Naranjo probability scale indicated probable causality for NMS due to quetiapine, haloperidol, and risperidone in this patient, whereas the Naranjo scale assigned only possible causality for serotonin syndrome developing with serotonergic agents. Laboratory investigations of blood and urine revealed elevations in dopamine, metanephrines, and epinephrines, as well as trazodone and risperidone. Serotonin metabolites were not elevated., Discussion: NMS is a rare and potentially severe adverse effect associated with the use of antipsychotic medications. It is mainly characterized by hyperthermia, altered mental state, hemodynamic dysregulation, elevated serum creatine kinase, and rigors. It has been associated with multisystem organ failure potentially leading to rhabdomyolysis, acute respiratory distress syndrome, and disseminated intravascular coagulation. The prevalence of this syndrome is associated with the use of neuroleptics. Serotonin syndrome is another adverse drug reaction leading to NMS associated with elevated serotonin. It occurs when multiple serotonergic medications are ingested and is associated with rapid onset of altered mental status, myoclonus, and autonomic instability. Differentiating between NMS and serotonin syndrome can be challenging because of their similar clinical presentation. This case highlights the importance of a diagnostic aid being available to help distinguish between the 2 syndromes., Conclusions: We propose that laboratory findings that include dopamine and serotonin metabolites can be used as adjuncts to clinical and prescription histories in the diagnosis of NMS. The use of urinary catecholamine as a diagnostic aid in NMS needs further evaluation.

Objective: To report a case of myoclonus that developed after administration of dextromethorphan., Case Summary: A 64-year-old man was diagnosed with chronic renal failure due to diabetic nephropathy. The patient started on peritoneal dialysis 6 months before he was hospitalized. Two days before hospitalization, he developed cough and sputum and he visited an outpatient clinic, where dextromethorphan was prescribed. After taking a total of 30 mg of dextromethorphan, the patient developed myoclonus, tremor, agitation, slurred speech, and diaphoresis, which continued after he stopped taking the prescribed medicine. He visited an emergency department and was hospitalized for examination and treatment of myoclonus., Discussion: As the patient's dialysis schedule was adequate, these symptoms were likely not due to uremia. The blood concentration of dextromethorphan (2.68 ng/mL) 60 hours after the 30-mg dose was higher than expected, and the blood concentration of dextrorphan, a metabolite, was lower than expected. We suspected that myoclonus was due to dextromethorphan-related symptoms induced by CYP2D6, which primarily metabolizes dextromethorphan. We analyzed the CYP2D6 gene for polymorphisms and identified CYP2D6 (*)1/(*)10. The patient had been taking metoprolol 40 mg/day for 2 years. The blood concentration of metoprolol 6 hours after administration was 13 ng/mL, which suggests that it was metabolized normally. Metoprolol has another metabolic pathway, via CYP2C19, and this may have led to its lack of accumulation. Moreover, metoprolol may have bound to active CYP2D6. Thus, affinity for CYP2D6, protein-binding rate, and lipid solubility may influence these drug interactions. Total scores for the Adverse Drug Reaction (ADR) probability scale and the Drug Interaction Probability Scale (DIPS) were 9 (highly probable) and 3 (possible), respectively., Conclusions: Myoclonus and other symptoms in this patient may have been caused by a prolonged high concentration of dextromethorphan due to CYP2D6 polymorphisms and drug interactions.

Objective: To report a case of quetiapine/venlafaxine intoxication associated with multiple complications and to review their possible relationship with these 2 drugs., Case Summary: A 53-year-old white man was admitted to the hospital for loss of consciousness secondary to voluntary intoxication with venlafaxine and quetiapine. Several complications were attributable to this intoxication including seizures, prolonged coma, respiratory depression, neuroleptic malignant syndrome, prolonged QRS and QTc intervals, and a possible venlafaxine withdrawal syndrome., Discussion: Quetiapine could be responsible for the neuroleptic malignant syndrome presented in this case. Moreover, venlafaxine intoxication, fever, autonomic instability, and myoclonus presented serotonin syndrome as a differential diagnosis. Potential causes of seizures and prolongation of the QRS and QTc intervals are reviewed. Finally, prolonged coma and late venlafaxine withdrawal are discussed with regard to the pharmacodynamics and pharmacokinetics of drug elimination in the context of intoxication., Conclusions: Clinicians should be aware of possible complications following intoxication with atypical antipsychotics and anti-depressants, including protracted altered mental status.