CONFERENCE REPORTER
Investigators introduced new knowledge on adjunctive lumateperone for the remedy of main depressive dysfunction (MDD) and potential comorbidities by way of poster shows on the thirty eighth European School of Neuropsychopharmacology (ECNP) Annual Congress, on October 11-14, 2025, in Amsterdam. Outcomes present that remedy with antidepressants plus lumateperone led to vital enhancements in signs of anhedonia, sexual dysfunction, and a broad vary of different depressive signs.1-3
Anhedonia happens in roughly 70% of people with MDD and is related to extreme and recurrent sickness, decreased high quality of life, and impaired functioning.4,5 In the meantime, sexual dysfunction happens in roughly 68% of people with MDD, with sufferers who take antidepressants experiencing every part from new or worsening sexual dysfunction, to decreased sexual need, sexual pleasure, and orgasmic perform—all of which negatively impacts high quality of life and reduces remedy adherence.6,7 Novel, efficient remedies with minimal opposed results are wanted for sufferers with MDD.
Lumateperone—a simultaneous modulator of serotonin, dopamine, and glutamate neurotransmission—is a mechanistically novel antipsychotic that’s accepted by the US Meals and Drug Administration to deal with schizophrenia and depressive episodes related to bipolar I or bipolar II dysfunction as monotherapy and as adjunctive remedy with lithium or valproate.
Two section 3, randomized, double-blind, placebo-controlled, multicenter research sought to raised perceive the impact of lumateperone 42 mg adjunctive to antidepressant remedy (ADT): Research 501 (NCT04985942) and Research 502 (NCT05061706).
Research 501
In Research 501, lumateperone 42 mg + ADT considerably improved depressive signs and illness severity in sufferers with MDD with insufficient response to ADT. As to security profile, lumateperone 42 mg + ADT was typically protected and effectively tolerated. Investigators analyzed the broad efficacy of lumateperone 42 mg + ADT throughout melancholy signs, as assessed by Montgomery-Åsberg Melancholy Score Scale (MADRS) single merchandise and anhedonia issue scores. Sufferers had been randomly assigned 1:1 to 6-week remedy with oral lumateperone 42 mg + ADT or placebo + ADT. The first endpoint was change in MADRS Complete rating from baseline to day 43. The MADRS Complete rating and the MADRS anhedonia issue rating had been analyzed in sufferers with an anhedonia baseline larger than the median, outlined as baseline MADRS anhedonia better than or equal to 18.
Lumateperone +ADT met the first endpoint, with vital enchancment in MADRS whole rating at day 43 in contrast with placebo + ADT (P<.0001). Investigators famous that probably the most outstanding MADRS single objects at baseline had been reported unhappiness and obvious unhappiness. Then, at day 43, lumateperone + ADT considerably improved all MADRS single objects, besides suicidal ideas, in contrast with placebo + ADT, with the most important enchancment in decreased sleep. The earliest vital (P<.05) reductions from baseline occurred at day 8 for reported unhappiness, obvious unhappiness, and decreased sleep; these enhancements continued all through the examine. There have been vital enhancements in incapacity to really feel and pessimistic ideas noticed at day 15, persisting as much as day 43. There have been additionally constant vital enhancements for internal stress and focus difficulties starting at day 22, and for decreased urge for food and lassitude starting at day 29. In sufferers with anhedonia baseline larger than the median, lumateperone 42 mg + ADT considerably improved each melancholy and anhedonia signs in contrast with placebo + ADT.
Research 502
In Research 502, lumateperone 42 mg/day adjunctive to antidepressants considerably improved depressive signs in contrast with placebo adjunctive to antidepressants, as measured by each clinician-rated and patient-rated outcomes, in sufferers with MDD with insufficient ADT response. Lumateperone 42 mg/day + ADT demonstrated no notable modifications in cardiometabolic parameters or physique morphology and a low threat of extrapyramidal signs. Investigators sought to grasp the influence of lumateperone 42 mg/day + ADT on sexual functioning, assessed by the Adjustments in Sexual Functioning Questionnaire 14-item model (CSFQ-14), in sufferers with MDD with insufficient ADT response. The first endpoint was the change from baseline to Day 43 in MADRS whole rating, analyzed utilizing a mixed-effects mannequin for repeated measures. Lumateperone 42 mg/day + ADT considerably improved sexual perform in contrast with placebo + ADT.
Concluding Ideas
These outcomes help lumateperone 42 mg/day as a promising adjunctive remedy possibility in sufferers with MDD with insufficient ADT response.
References
1. Earley WR, Durgam S, Kozauer SG, et al. Efficacy of adjunctive lumateperone 42 mg remedy throughout melancholy and anhedonia signs in main depressive dysfunction. Poster introduced at: thirty eighth European School of Neuropsychopharmacology Annual Congress; October 11-14, 2025; Amsterdam, The Netherlands. Accessed October 10, 2025.
2. Thase ME, Earley WR, Kozauer SG, et al. Adjunctive lumateperone 42 mg remedy in main depressive dysfunction: efficacy in anhedonia and throughout broad vary of depressive signs. Poster introduced at: thirty eighth European School of Neuropsychopharmacology Annual Congress; October 11-14, 2025; Amsterdam, The Netherlands. Accessed October 10, 2025.
3. Clayton AH, Earley WR, Kozauer SG, et al. Analysis of sexual perform with adjunctive lumateperone in sufferers with main depressive dysfunction. Poster introduced at: thirty eighth European School of Neuropsychopharmacology Annual Congress; October 11-14, 2025; Amsterdam, The Netherlands. Accessed October 10, 2025.
4. Whitton AE, Pizzagalli DA.
5. Serretti A.
6. Jacobsen P, Zhong W, Nomikos G, Clayton A.
7. Rothmore J.