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INTRODUCTION: Major Depressive Disorder (MDD) is a common mental health disorder marked by sadness, hopelessness, and anhedonia. Various therapies exist, but their effectiveness is limited. Dextromethorphan hydrobromide combined with bupropion hydrochloride (Auvelity®) is a recently approved alternative for treating this condition in adults. AREAS COVERED: This review summarizes the neurobiology of major depression and delves into the pharmacology, efficacy, safety, and tolerability of dextromethorphan plus bupropion in adult patients. It is based on observational studies, clinical trials, and other secondary studies obtained through systematic literature searches. EXPERT OPINION: The combination of bupropion and dextromethorphan as a new pharmacotherapy for mental health is an interesting addition to the treatment options that can be used for MDD. The combination can be used in a range of scenarios, including as a first line therapy, as a second option when a patient has failed to achieve remission with a serotonin targeting agent, and for treatment resistant depression. Further research for other indications, including addiction disorders, may provide exciting results. Although a new combination, clinicians will be very familiar with both agents, increasing their acceptability. This pharmacotherapy also may bring increased impetus for discovering other combinations that may have beneficial synergistic effects.

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A case report of a patient with pseudo bulbar affect previous treatments included haloperidol (10mg), Inosina pranobex (600mg), clozapine (600mg), olanzapine (20mg), carbamazepine (200mg), paroxetine (20mg), phenobarbital (100mg) and topiramate (50mg), all suspended at August 2016, with current use of quetiapine (700mg) Chlorpromazine (600mg) (+ 200mg on demand of aggression), clonazepam (4 mg), valproate 2500 mg, propranolol (40mg). that was successful treated with off label treatment (dextromethorphan plus quinidine). Previous Brief Psychiatric Rating Scale and Clinical Global Impression-Improvement was applied after and before treatment with dextromethorphan (20mg) plus fluoxetine (20 mg, further increased to 40 mg). Previous Brief Psychiatric Rating Scale BPRS score 56 points and Clinical Global Impression-Severity (CGI-S) Score was 6 (severely ill). The addition of dextromethorphan (20mg) and fluoxetine (20 mg, further increased to 40 mg), allowed clear improvement of pathological crying and outbursts, with BPRS decrease of 8 points and Clinical Global Impression-Improvement (CGI-I) 2 (much improved) ­ especially pertaining to PBA related symptoms and aggressive behavior. There were no noticeable side-effects. This case report shown an interesting clinical response. It's could be a great alternative in treatment of pseudobulbar affect symptoms. Even though an only case and a great clinical study be necessary. (AU)

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A partir de una consulta en la central de emergencias de un niño con tos aguda, el autor del artículo realiza una búsqueda bibliográfica para revisar la evidencia sobre el uso de la miel para aliviar este síntoma. Luego de la lectura crítica de una revisión sistemática, el autor concluye que ésta podría ser una alternativa elegible frente a los jarabes para la tos, por su perfil de seguridad y su posible beneficio en el alivio de la tos. (AU)

Based on a consultation at the emergency room of a child with acute cough, the author of this article performs a bibliographic search to review the evidence on the use of honey to alleviate this symptom. After the critical appraisal of a systematic review, the author concludes that honey could be an eligible alternative to cough syrups, due to its safety profile and its possible benefit in cough relief. (AU)

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OBJECTIVE: To evaluate the impact of sodium benzoate and dextromethorphan treatment on patients with the attenuated form of nonketotic hyperglycinemia. STUDY DESIGN: Families were recruited with 2 siblings both affected with attenuated nonketotic hyperglycinemia. Genetic mutations were expressed to identify residual activity. The outcome on developmental progress and seizures was compared between the first child diagnosed and treated late with the second child diagnosed at birth and treated aggressively from the newborn period using dextromethorphan and benzoate at dosing sufficient to normalize plasma glycine levels. Both siblings were evaluated with similar standardized neurodevelopmental measures. RESULTS: In each sibling set, the second sibling treated from the neonatal period achieved earlier and more developmental milestones, and had a higher developmental quotient. In 3 of the 4 sibling pairs, the younger sibling had no seizures whereas the first child had a seizure disorder. The adaptive behavior subdomains of socialization and daily living skills improved more than motor skills and communication. CONCLUSIONS: Early treatment with dextromethorphan and sodium benzoate sufficient to normalize plasma glycine levels is effective at improving outcome if used in children with attenuated disease with mutations providing residual activity and when started from the neonatal period.

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Ischemia/reperfusion (I/R) is a condition that stimulates an intense inflammatory response. No ideal treatment exists. Triflusal is an antiplatelet salicylate derivative with anti-inflammatory effects. S-adenosylmethionine is a metabolic precursor for glutathione, an endogenous antioxidant. Dextromethorphan is a low-affinity N-methyl-D-aspartate receptor inhibitor. There is evidence that these agents modulate some of the pathways involved in I/R physiopathology. Intestinal I/R was induced in rats by clamping the superior mesenteric artery for 60 minutes, followed by 60 minutes of reperfusion. Rats either received saline or the drugs studied. At the end of the procedure, serum concentrations of tumor necrosis factor-alpha (TNF-alpha), malonaldehyde (MDA), and total antioxidant capacity (TAC) were determined and intestinal morphology analyzed. I/R resulted in tissue damage, serum TNF-alpha and MDA elevations, and depletion of TAC. All drugs showed tissue protection. Only triflusal reduced TNF-alpha levels. All drugs lowered MDA levels, but only triflusal and S-adenosylmethionine maintained the serum TAC.

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OBJECTIVE: The objective of this study was to test the hypotheses that reduction of glycine and blocking of the N-methyl-D-aspartate receptor channel complex would be beneficial for both seizure reduction and developmental progress in patients with nonketotic hyperglycinemia. METHODS: We administered benzoate (at doses of 500 to 750 mg/kg/day) and dextromethorphan (at doses of 3.5 to 22.5 mg/kg/day) to four infants with nonketotic hyperglycinemia with follow-up of 3 months to 6 years. RESULTS: Benzoate reduced to normal the glycine concentration in plasma and substantially reduced but did not normalize the glycine concentration in cerebrospinal fluid. Dextromethorphan was a potent anticonvulsant in some but not all patients. There was remarkable interpatient variability in dextromethorphan metabolism. Three patients are living (ages ranging from 4 to 6 years) and are moderately to severely developmentally delayed; two are free of seizures. The third patient, with the slowest development, had intractable seizures for nearly a month before diagnosis, and although seizure-free for 30 months, now has grand-mal seizures. One patient died of intractable seizures at 3 months. CONCLUSIONS: These outcomes suggest that benzoate and dextromethorphan are not uniformly effective in nonketotic hyperglycinemia, but for some patients they improve arousal, decrease or eliminate seizures, and allow for some developmental progress. Trials with additional patients and other receptor channel blockers are warranted.

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To test the hypothesis that codeine and dextromethorphan are effective in alleviating the symptoms of acute cough, we conducted a randomized, controlled trial. Eligible patients were children 18 months to 12 years of age, seen in private pediatric practices, with significant night cough of less than 14 days' duration. Study patients were randomly selected to receive codeine, dextromethorphan, or placebo at bedtime for 3 consecutive nights. Outcomes were assessed by the use of a parent questionnaire rating the severity of symptoms at the initiation of therapy, and after each night of the study. Every patient had a cough score (range 0 to 4) and composite symptom score (range 0 to 9) computed for each day of the study. One hundred forty-one doses of study medication were evaluated in 49 patients, including 13 children receiving placebo, 19 dextromethorphan, and 17 codeine. Mean cough and composite symptom scores decreased in each of the three treatment groups on each day of the study; there were no significant differences. Regression analysis, with reduction in cough score as the outcome of interest, showed that neither dextromethorphan nor codeine was significantly more effective than placebo (p = 0.41 and 0.70, respectively). Reduction in cough score was positively correlated with the severity of cough at the start of treatment (p = 0.007). Our data suggest that, in the doses used, neither codeine nor dextromethorphan is superior to placebo in treating night cough in children.

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To test the hypothesis that nonketotic hyperglycinemia causes overstimulation of the excitatory N-methyl-D-aspartate receptor by allosteric glycine activation, and that reduction of glycine and blocking of the cation channel coupled to the receptor would be beneficial, we administered benzoate and dextromethorphan, a blocker of the N-methyl-D-aspartate channel to an infant with nonketotic hyperglycinemia. Therapy with benzoate, 500 mg/kg per day, was started on day 5, and the dosage was increased to 750 mg/kg per day on day 8, with prompt normalization of the neurologic and electroencephalographic findings. The glycine concentrations in both plasma and cerebrospinal fluid were substantially reduced. Dextromethorphan was added to the regimen on day 12. The electroencephalogram remained normal until the infant was 8 months of age, when diffuse slowing became apparent. Serial brain magnetic resonance imaging showed delayed myelination. At 12 months of age, physical examination findings and growth were normal except for hypotonia. The developmental quotient was approximately 60, and the child was free of seizures. This outcome, although not ideal, is better than that typical for nonketotic hyperglycinemia. Our results suggest that trials with additional patients and other N-methyl-D-aspartate cation channel blockers are warranted.

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