Depression is a significant cause of morbidity and mortality globally. Although various pharmacologic options exist for depression, treatments are limited by delayed or incomplete therapeutic response, low rates of remission, and adverse effects necessitating effective, fast-acting, and better tolerated alternatives. The purpose of this review is to describe the safety and efficacy of dextromethorphan-bupropion (Auvelity), a Food and Drug Administration approved treatment for major depressive disorder in adults. Dextromethorphan modulates glutamate signaling through uncompetitive antagonism of N-methyl-D-aspartate receptors and sigma-1 agonism, while bupropion increases the bioavailability of dextromethorphan by CYP2D6 inhibition. In a phase 3 trial with dextromethorphan-bupropion 45−105 mg for patients with major depressive disorder saw significant reductions in their Montgomery–Åsberg Depression Rating Scale total scores compared to placebo. A phase 2 trial comparing dextromethorphan-bupropion 45−105 mg to bupropion monotherapy led to significant reduction in Montgomery-Åsberg Depression Rating Scale score. Changes in Montgomery–Åsberg Depression Rating Scale with dextromethorphan-bupropion were seen within two weeks in both clinical trials. Remission and response rates were significantly higher with dextromethorphan-bupropion in both studies. The medication was well-tolerated in both trials, with the most common adverse events being rated as mild-to-moderate. Two long-term, open-label studies with dextromethorphan-bupropion saw large reductions in Montgomery–Åsberg Depression Rating Scale scores that were maintained through 12 and 15 months of treatment. In both long-term studies, remission rates approached 70%, while response rates were greater than 80%. These data suggest that dextromethorphan-bupropion is an effective, fast-acting, and well tolerated option for depression treatment and produced remission in a large percentage of patients.

Acute agitation is common amongst individuals with bipolar disorder and schizophrenia and represents a medical emergency. Commonly used medications for agitation, such as benzodiazepines and antipsychotics, are often delivered intramuscularly and may cause adverse effects. Non-invasive, effective, and safe alternative treatment options are needed.The purpose of this review article is to describe the efficacy and safety of sublingual formulation of dexmedetomidine (Igalmi), a selective α2-adrenergic receptor agonist, U.S. Food and Drug Administration approved for the treatment of acute agitation in adults with schizophrenia or bipolar I and II disorder. In two phase 3 trials, two dose strengths of sublingual dexmedetomidine 180 μg and 120 μg were safe and effective in managing acute agitation in patients with bipolar disorder or schizophrenia. Both doses significantly reduced Positive and Negative Syndrome Scale-Exited Component scores two hours after receiving a single dose as compared to placebo, indicating a substantial improvement in agitation. The beneficial effects of sublingual dexmedetomidine were achieved without serious adverse events with the most common side effect being mild somnolence. The clinical trial data suggest that sublingual dexmedetomidine represents a safe and effective treatment option in the armamentarium for acute agitation for people with schizophrenia or bipolar disorder.

There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.
Genetic Predisposition to Disease ; genetics ; Genetic Testing ; Humans ; Kallikreins ; genetics ; Male ; Membrane Proteins ; genetics ; Prostatic Neoplasms ; diagnosis ; genetics ; Prostatic Secretory Proteins ; genetics ; Protein-Serine-Threonine Kinases ; genetics ; Risk Factors