A network meta-analysis of two randomized controlled trials found that the dextromethorphan-bupropion combination (AXS-05) is more effective than either bupropion alone or placebo for treating major depressive disorder. Remission rates were 46.5% and 39.5% for the combination, compared to 16.2% for bupropion alone and 17.3% for placebo. Mild to moderate adverse events occurred more often with the combination (72.9%) than with bupropion alone (64.6%), but treatment discontinuation rates were not significantly different. The authors suggest AXS-05 is a promising treatment, though further research in larger, diverse populations is needed to confirm long-term efficacy and safety.
Drug development is lengthy, complex, and costly. In 2004, the FDA's 'Critical Path' document highlighted a gap between scientific advances and the drug development process, addressing microdosing. Microdosing uses extremely low, nonpharmacologically active doses to determine a drug's pharmacokinetic profile in humans. It offers a new tool that could complement traditional animal-to-human scaling and reshape phase I clinical research. As Phase 0 methods and technology advance, human microdosing may become applicable to more drugs in development.
Phencyclidine (PCP), a drug that induces psychotic symptoms resembling schizophrenia, blocks NMDA glutamate receptors in the brain. This experiment tested whether surgically removing the olfactory bulbs in rats altered the effects of a single high dose of PCP (10 mg/kg) on behavior. PCP increased home-cage movement in both bulbectomized and sham-operated animals over three hours, with slightly greater activity in the sham group. PCP also suppressed grooming, rearing, and side-falling while increasing circling and head rolling in both groups, though these behavioral changes were not statistically significant. The results suggest that olfactory bulb removal does not alter NMDA receptor activity.