CNS Spectrums
April 1, 2023
Amanda Jones, Caroline Streicher, Shawn Alter et al.
An open-label study tested AXS-05, a combination of dextromethorphan and bupropion, in 146 directly enrolled patients with major depressive disorder and comorbid anxiety. Mean baseline HAM-A anxiety scores were 15.6. Reductions from baseline were 3.4 points at Week 1, 5.5 at Week 2, and 8.6 at Week 6, with improvements lasting through Month 12. Remission rates (HAM-A ≤7) reached 58.1% by Week 6 and 78.3% at Month 12. Common side effects included COVID-19 infection, nausea, headache, dry mouth, insomnia, and dizziness. The authors suggest the treatment is useful for patients with both depression and anxiety.
CNS Spectrums
April 1, 2023
Amanda Jones, Caroline Streicher, Shawn Alter et al.
AXS-05 (dextromethorphan-bupropion) is an oral NMDA receptor antagonist being developed for major depressive disorder. In two double-blind, randomized, controlled 6-week trials, AXS-05 showed rapid antidepressant effects. In the placebo-controlled GEMINI trial (327 participants), AXS-05 was superior to placebo on depressive symptom improvement starting at Week 1, with greater improvement on the MADRS scale (7.3 vs. 4.9 points), higher response rates (15% vs. 7%), and by Week 2, higher remission rates (17% vs. 8%). In the ASCEND trial (80 participants) comparing AXS-05 to bupropion alone, AXS-05 was superior from Week 2 on MADRS improvement (12.5 vs. 7.8 points) and remission (26% vs. 3%). Common adverse events included dizziness, nausea, headache, diarrhea, somnolence, and dry mouth.
CNS Spectrums
April 1, 2023
Amanda Jones, Caroline Streicher, Shawn Alter et al.
In patients with major depressive disorder who had not improved after one prior antidepressant in the current episode, treatment with AXS-05 (dextromethorphan HBr 45 mg-bupropion HCl 105 mg) led to rapid and sustained improvements in depression and functioning. Mean scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) dropped by 9.1 points at one week, 13.3 points at two weeks, and 20.4 points at six weeks. Remission (MADRS score of 10 or less) was achieved by 5.7% of patients at one week, 16.2% at two weeks, and 46.0% at six weeks. Improvements in functioning were seen starting at one week and were maintained at 12 months. Common side effects included COVID-19 infection, nausea, headache, dry mouth, insomnia, and dizziness.
CNS Spectrums
April 1, 2023
Amanda Jones, Roger S McIntyre, Mark Jacobsen et al.
AXS-05 (dextromethorphan-bupropion) rapidly and significantly reduced anhedonic symptoms in adults with major depressive disorder. In a 6-week randomized, double-blind, placebo-controlled trial with 327 participants, those receiving AXS-05 showed a mean reduction of 4.44 points on the MADRS anhedonia subscale at Week 1 versus 2.69 points for placebo, and a reduction of 9.70 points at Week 6 versus 7.22 for placebo. Response rates were significantly greater for AXS-05 from Week 1 onward. Common adverse events included dizziness, nausea, and headache.
CNS Spectrums
September 30, 2019
S. Stahl
Standard antidepressants boost monoamine levels quickly, but therapeutic effects often take weeks and many patients with major depressive disorder do not respond adequately to first- or second-line monoamine-targeting treatments. The recent approval of the NMDA antagonist esketamine (intranasal) for treatment-resistant depression highlights the need for rapid-acting drugs with different mechanisms. Dextromethorphan/bupropion, an investigational medicine in development, is one such candidate.
CNS Spectrums
February 1, 2003
Alan B Douglass
Narcolepsy may be underdiagnosed in psychiatric patients because its hypnagogic hallucinations can be mistaken for schizophrenia or lead to a more severe bipolar diagnosis. The article reviews the clinical tetrad of narcolepsy—cataplexy, hypnagogic hallucinations, daytime sleep attacks, and sleep paralysis—and the role of orexin/hypocretin neuron loss, likely autoimmune. It argues that classical narcolepsy can now be ruled out in difficult psychiatric cases, and that psychotic patients with narcolepsy may need stimulants for recovery, as conventional antipsychotics could worsen symptoms.