SAN FRANCISCO—Treatment with a novel combination of 2 common medications was associated with “a rapid and significant reduction in symptoms of depression,” compared with treatment with one of the components, according to a poster presented at the American Psychiatric Association’s Annual Meeting.
Eighty adults with moderate or severe major depressive disorder were randomized to the combination drug, AXS-05, or bupropion in the 6-week trial. AXS-05 consists of dextromethorphan, the active ingredient in Robitussin cough medicine, and bupropion, a popular antidepressant.
Patients taking AXS-05 demonstrated a statistically significant mean reduction from baseline in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS). Their score declined by 13.7 points, compared with 8.8 points for the bupropion group.
Score differences were seen beginning at Week 1. In Week 6, the AXS-05 group had a 17.2 point reduction in the MADRS total score, vs a 12.1 point reduction for the bupropion group. Remission was achieved by 47% of the AXS-05 group, compared with 16% of the patients taking bupropion.
There were no serious adverse events experienced by patients in the trial. Nausea, dizziness, dry mouth, decreased appetite, and anxiety were the most commonly reported side effects.
The poster also presented data from a phase 2 trial on smoking cessation, showing AXS-05 treatment was associated with a significant reduction in the number of cigarettes smoked per day and exhaled carbon monoxide levels, compared with bupropion.
Poster presenter Cedric O’Gorman, MD, MBA, senior vice president, clinical development and medical affairs, of Axsome Therapeutics, said AXS-05 binds to the N-methyl-D-aspartate (NMDA) receptor, as ketamine does, but, unlike ketamine, it is taken orally.
Dextromethorphan is an NMDA receptor antagonist, sigma-1 receptor agonist and an inhibitor of norepinephrine and serotonin reuptake, according to the poster. In AXS-05, bupropion increases the bioavailability of dextromethorphan and is a norepinephrine and dopamine reuptake inhibitor, the poster states.
“Both components are nicotinic receptor antagonists and possess anti-inflammatory properties,” researchers wrote. “These mechanisms of action may be relevant for various neuropsychiatric conditions.”
Axsome is conducting 2 ongoing trials of AXS-05: a phase 3 study for treatment-resistant depression (TRD) and a phase 2/3 study for agitation in Alzheimer’s disease. The TRD study involves 250 adults who take bupropion for 6 weeks than are randomized to AXS-05 or bupropion for 6 weeks. In the Alzheimer’s study, 435 people are being randomized to AXS-05 or bupropion for 5 weeks.
The TRD study could be the second study needed for a New Drug Application which the company hopes to file with the US Food and Drug Administration next year, Dr. O’Gorman said.
“AXS-05: A mechanistically novel oral therapeutic in development for neuropsychiatric disorders.” Abstract presented at: the American Psychiatric Association Annual Meeting; May 21, 2019; San Francisco, CA.