New Phase 3 analysis shows CAPLYTA with an antidepressant nearly doubled remission rates in major depressive disorder, with durable benefits maintained for six months.
Written By: Nikita Chaudhari BPharm
Reviewed By: Pharmacally Editorial Team
Johnson & Johnson has reported new analyses from Phase 3 trials showing that CAPLYTA® (lumateperone), when used alongside standard antidepressants, achieved significantly higher remission rates in adults with major depressive disorder compared with antidepressants alone. The results were presented at the 64th Annual Meeting of the American College of Neuropsychopharmacology (ACNP) held January 12–15 in Nassau, Bahamas, as part of 11 abstracts highlighting advances from the company’s neuropsychiatry portfolio.
Bill Martin, Ph.D., Global Therapeutic Area Head for Neuroscience at Johnson & Johnson Innovative Medicine, said that many patients settle for partial improvement after years of trying different medications. These results, he said, show that complete relief should be a realistic expectation rather than an exception.
Major Depressive Disorder
Major depressive disorder remains one of the most common and disabling psychiatric illnesses. About 22 million adults in the United States live with the condition, and nearly two-thirds fail to reach remission with currently available therapies. Persistent symptoms are linked to impaired daily functioning, higher relapse risk, and a heavy economic burden. Experts increasingly emphasize that true remission, not partial improvement, should be the primary goal of treatment.
How the Analysis Was Conducted
The new evaluation pooled data from three Phase 3 studies of CAPLYTA:
Studies 501 and 502: two pivotal double-blind, placebo-controlled trials
Study 503: a six-month open-label extension assessing long-term outcomes
Researchers assessed remission using the Montgomery-Åsberg Depression Rating Scale (MADRS) with three definitions:
- Remission: MADRS score ≤10
- Complete remission: MADRS score ≤5
- Sustained remission: MADRS ≤10 at every assessment
This approach allowed investigators to measure both the depth and durability of symptom relief.
Key Findings
Six-Week Results from Pooled Pivotal Trials
- 25.5% of patients receiving CAPLYTA plus an antidepressant achieved remission compared with 13.6% on placebo plus antidepressant
- 10.6% reached complete remission versus 5.6% with placebo
- Benefits were consistent across age groups, antidepressant class, and baseline severity
Long-Term Outcomes from Study 503
Among 809 participants treated for six months:
- 65.4% achieved remission
- 44.1% achieved complete remission
- 42.8% experienced sustained remission throughout treatment
Rates of sustained remission increased steadily over time, rising from 28.6% at Week 8 to 40.8% at Week 24, suggesting durable benefit with continued therapy.
Safety and Tolerability
Across Studies 501 and 502, CAPLYTA showed a favourable safety profile:
- Most common adverse events were dizziness, dry mouth, somnolence, nausea, fatigue, and diarrhea
- Metabolic parameters and weight changes were similar to placebo
- Rates of extrapyramidal symptoms were low
In the 26-week extension study, changes in cardiometabolic measures, prolactin levels, blood pressure, and ECG readings were minimal. No emergence of serious suicidal ideation or behavior was reported.
Dr. Michael E. Thase of the University of Pennsylvania noted that remission remains out of reach for most patients with depression. He emphasized that the findings demonstrate not only symptom reduction but also meaningful durability, with adjunctive lumateperone nearly doubling the likelihood of remission over six months.
About CAPLYTA
CAPLYTA 42 mg is a once-daily atypical antipsychotic recently approved by the U.S. FDA in November 2025 as an adjunctive therapy for major depressive disorder. It is also indicated for schizophrenia and bipolar depression. The medication does not require dose titration, allowing patients to begin treatment at the therapeutic dose.
Although its exact mechanism is unknown, CAPLYTA shows high occupancy at serotonin 5-HT2A receptors and moderate activity at dopamine D2 receptors.
A supplemental New Drug Application is currently under FDA review to evaluate CAPLYTA for prevention of relapse in schizophrenia, and studies are ongoing in additional neuropsychiatric conditions.
Understanding MDD
Depression is a highly heterogeneous disorder with hundreds of possible symptom combinations, which helps explain why responses to treatment vary widely. Only about one in three patients achieve remission with their first antidepressant, and success rates decline with each subsequent attempt. These realities underscore the need for new adjunctive options that can deliver deeper and more durable recovery.
What Is the Difference Between the FDA Approval and the New 501, 502, 503 Analysis?
The November 2025 FDA approval of CAPLYTA was based on pivotal trials designed to show that adding lumateperone to an antidepressant improves overall depressive symptoms, measured by average change in MADRS score at six weeks.
The current 501, 502, and 503 analysis goes further by examining true remission and durability of response. Instead of only measuring symptom reduction, it evaluated how many patients achieved MADRS ≤10 or ≤5, and whether remission was sustained for up to six months.
References
New clinical data highlights CAPLYTA® (lumateperone) as a promising option for achieving remission in adults with major depressive disorder, 16 January 2026, https://www.jnj.com/media-center/press-releases/new-clinical-data-highlights-caplyta-lumateperone-as-a-promising-option-for-achieving-remission-in-adults-with-major-depressive-disorder
Clinical Trial of Lumateperone as Adjunctive Therapy in the Treatment of Patients with Major Depressive Disorder, ClinicalTrials.gov ID NCT04985942, https://www.clinicaltrials.gov/study/NCT04985942
Multicenter Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients with Major Depressive Disorder, ClinicalTrials.gov ID NCT05061706, https://www.clinicaltrials.gov/study/NCT05061706
Patients on CAPLYTA sustained treatment over 6 months, https://www.caplytahcp.com/long-term-data
FDA Approves CAPLYTA (Lumateperone) as Adjunctive Therapy for Major Depressive Disorder in Adults, 15 November 2025, https://pharmacally.com/fda-approves-caplyta-lumateperone-as-adjunctive-therapy-for-major-depressive-disorder-in-adults/