Key Takeaways
Extended Takeaways
- Patients meeting DSM-5 anxious distress criteria appeared to derive a larger antidepressant effect than those without anxious distress, with Day 43 MADRS effect sizes of 0.85 versus 0.44 and CGI-S effect sizes of 0.91 versus 0.50.
- Onset of benefit differed by subgroup: significant MADRS improvement with lumateperone+ADT emerged by Day 15 in patients with anxious distress and by Day 8 in those without anxious distress, while CGI-S separated from placebo by Day 22 and Day 8, respectively.
- Response and remission outcomes were especially strong in major depressive disorder with anxious distress, where the NNTs were 3 for MADRS response and 7 for remission, compared with 9 and 10 in patients without anxious distress.
- Anxiety-specific improvement was concentrated in the anxious distress subgroup: GAD-7 change at Day 43 was significant in patients with anxious distress but not in those without anxious distress (P =.379), and the discussion reports an LSMD of −3.2 in the anxious distress group.
- Tolerability remained generally favorable across subgroups, with minimal changes in metabolic parameters and prolactin levels; among lumateperone-treated patients, discontinuation due to adverse events was 4.5% with anxious distress and 6.9% without anxious distress.
- This analysis used DSM-5 anxious distress criteria confirmed with the MINI anxious distress module, but applicability may be narrower in routine practice because patients with a primary anxiety disorder, anxiety symptoms needing concurrent treatment, or concomitant benzodiazepines and nonbenzodiazepine anxiolytics were excluded.
