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CAPLYTA® ranked highest among FDA-approved adjunctive therapies across four measures of efficacy, based on indirect comparisons from placebo plus antidepressant therapy-controlled trials
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Among the secondary endpoints for the adjunctive MDD therapies evaluated, CAPLYTA® demonstrated no weight gain compared to placebo plus antidepressant therapy
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Featured in a late-breaking presentation at the 2026 NEI Spring Congress, analysis provides indirect comparisons to help inform treatment decisions in the absence of head-to-head clinical trials
TITUSVILLE, N.J., May 4, 2026 -- Johnson & Johnson (NYSE: JNJ) today announced findings from the first network meta-analysis (NMA) comparing CAPLYTA® (lumateperone) to FDA-approved atypical antipsychotics for add-on treatment of major depressive disorder (aMDD) in adults, drawing on data from 10 registrational randomized clinical trials. The NMA found that CAPLYTA® was favored for the efficacy outcomes across four measures, based on indirect comparisons derived from placebo plus antidepressant therapy (ADT)-controlled trials. The analysis also evaluated safety outcomes, with CAPLYTA® demonstrating no statistically significant weight gain compared to placebo plus ADT and favorable rankings on select tolerability measures.1 The data were featured in a late-breaking presentation at the 2026 Neuroscience Education Institute (NEI) Spring Congress, held from May 1-3, in Kissimmee, Florida.
“The goal of treating patients with MDD should be remission of symptoms, which may mean adding to their current treatment in order to achieve the best outcomes,” said Andrew J. Cutler, M.D., lead author of the analysis and Chief Medical Officer, Neuroscience Education Institute and Clinical Professor of Psychiatry at SUNY Upstate Medical University.* “This analysis is valuable because it gives us indirect comparative insights in a space where we don’t have head-to-head trials, which may inform treatment discussions in everyday clinical practice. The findings suggest adjunctive lumateperone has a high likelihood of helping patients achieve meaningful improvement in symptoms. Symptom improvement is an important step toward remission, the ultimate goal of treatment.”
Detailed Findings and Methodology
The NMA is a widely used method to indirectly compare treatments evaluated in separate placebo-controlled trials.2-5 To reflect clinical decision-making at the treatment level, doses were pooled within treatments in this analysis, resulting in a star-shaped network comprising five treatment nodes anchored on placebo plus ADT. Outcomes were selected based on availability of data across the identified clinical trials and comprised four efficacy outcomes – change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) score, MADRS response†, MADRS remission‡, and change from baseline in CGI-S score – and four safety outcomes: weight change from baseline, incidence of clinically meaningful weight increase, akathisia, and somnolence. Additional safety and tolerability outcomes were not assessed in this NMA due to inconsistent reporting across trials.1
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Efficacy: CAPLYTA® was favored for the efficacy outcomes across four measures, with the largest effect size among all five treatment nodes evaluated: MADRS change from baseline (mean difference [MD] -4.71; 95% credible intervals [CrI] -5.78, -3.63), MADRS response (odds ratio [OR 2.33]; 95% CrI 1.77, 3.05), MADRS remission (OR 2.22; 95% CrI 1.57, 3.07), and CGI-S change from baseline (MD -0.60; 95% CrI -0.74, -0.46).
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In pairwise treatment comparisons anchored to CAPLYTA®, CAPLYTA® was favored across all comparators for MADRS and CGI-S change from baseline, and versus all but one comparator for MADRS response and MADRS remission.
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Weight: CAPLYTA® demonstrated no statistically significant weight gain compared to placebo plus ADT, ranking most favorably among all treatments evaluated on both weight-related outcomes: mean weight change from baseline (MD -0.08; 95% CrI -0.30, 0.13; 77% probability of superiority) and proportion of patients with a clinically meaningful weight increase of ≥7% (OR 0.41; 95% CrI 0.04, 1.42; 94% probability of lower risk).
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CAPLYTA® had a 100% probability of superiority versus all comparators on mean weight change.
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Akathisia (inner restlessness): CAPLYTA® was the only treatment comparable to placebo plus ADT for the risk of akathisia (OR 3.78; 95% CrI 0.40, 17.17); the remaining four treatments evaluated showed higher akathisia risk than placebo plus ADT.
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Somnolence: Somnolence risk was higher than placebo plus ADT across all treatments evaluated (CAPLYTA® OR 5.90; 95% CrI 2.86, 11.50). In pairwise comparisons, CAPLYTA® showed comparable risk versus two treatments and higher risk versus two treatments.
“The adjunctive treatments approved for MDD share a common indication but differ in their pharmacologic profiles, efficacy, and tolerability,” said Leonardo Diaz, M.D., Vice President, U.S. Medical Affairs, CAPLYTA®, Johnson & Johnson. “This NMA provides indirect comparative evidence derived from placebo-controlled studies that may help inform treatment decisions, reinforcing the role of CAPLYTA as an important treatment option for the many adults with MDD who do not achieve adequate symptom control with an antidepressant alone.”
NMA is a structured, protocol-driven analytical process widely accepted and utilized by regulatory agencies, health technology assessment agencies, and medical guideline committees to compare treatment options when head-to-head trials are limited or unavailable. As NMAs rely on indirect comparisons across studies that can differ in design and patient populations, findings should be interpreted cautiously alongside the totality of evidence, including individual trial results and clinical considerations.2-5
Editor’s note:
* Andrew J. Cutler, M.D., has provided consulting, advisory, and speaking services to Johnson & Johnson. He has not been paid for any media work.
† Clinical response was defined as ≥50% reduction in MADRS score from baseline.
‡ Remission was defined as MADRS score ≤10, or MADRS score ≤10 with ≥50% reduction from baseline, depending on the trial.
About Major Depressive Disorder (MDD)
MDD is one of the most common psychiatric disorders and a leading cause of disability worldwide, impacting an estimated 332 million people – or about 4 percent of the population.6 In the U.S. alone, about 22 million adults are living with the disease.7 While depression is typically treated with a “one-size-fits-all” approach, no two cases are the same. MDD is a complex, heterogeneous disorder involving multiple regions of the brain and presenting with as many as 256 unique symptom combinations. As a result, responses to treatment vary widely.8-9 Only 1 in 3 patients reach remission with their first antidepressant, and rates continue to decline further with each subsequent treatment – leaving many to spend years cycling through multiple treatments trying to find complete, sustained symptom relief.10-11 Moreover, MDD is a risk factor for the development and worsening of a range of comorbidities, illustrating the importance of integrating mental and general health care.12
About the Network Meta-Analysis
The NMA evaluated the comparative efficacy and safety of five atypical antipsychotics approved by the FDA as adjunctive therapy for adults with MDD, including aripiprazole (Abilify®), brexpiprazole (Rexulti®), cariprazine (Vraylar®), lumateperone (CAPLYTA®) and quetiapine XR (Seroquel XR®). The analysis included 10 randomized, double-blind, parallel-group, placebo-controlled trials identified through a systematic literature review using Section 14: Clinical Studies in the U.S. Prescribing Information of each of the five products. A Bayesian statistical framework with a star-shaped network design was used, with ADT plus placebo as the common comparator, enabling indirect comparative estimates for efficacy outcomes (MADRS change from baseline, MADRS response, MADRS remission, and CGI-S change from baseline) and safety outcomes (weight change from baseline, weight increase of 7% or more, akathisia, and somnolence).1
This NMA adheres to all governing standards and requirements as demanded by global health technology assessment agencies, journal review committees and regulatory authorities. The NMA was funded by Janssen Research & Development, LLC.
About CAPLYTA® (lumateperone)
CAPLYTA® 42 mg is an oral, once daily atypical antipsychotic approved in adults as an adjunctive therapy with antidepressants for major depressive disorder (MDD), schizophrenia, and depressive episodes associated with bipolar I or II disorder (bipolar depression), as monotherapy, and as adjunctive therapy with lithium or valproate.
While the mechanism of action of CAPLYTA® is unknown, the efficacy of CAPLYTA® could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and partial agonist activity at central dopamine D2 receptors.
A supplemental New Drug Application (sNDA) for CAPLYTA® with long-term data evaluating the safety and efficacy of the medication for delayed time to relapse in schizophrenia was recently approved by the U.S. Food and Drug Administration. The medication is also being studied for other neuropsychiatric disorders. CAPLYTA® is not FDA-approved for these disorders.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow and profoundly impact health for humanity.
Footnotes
1 Cutler AJ, Lemyre A, Zhang Q, et al. Efficacy and Safety of Lumateperone versus Atypical Antipsychotics as Adjunctive Therapy in Major Depressive Disorder: A Pooled-Dose Network Meta-Analysis. 2026 Neuroscience Education Institute (NEI) Spring Congress; May 1-3, 2026; Kissimmee, FL.
2 Dias, S., et al. Evidence Synthesis for Decision Making 2. Medical Decision Making, 2012:33(5), 607–617. https://doi.org/10.1177/0272989x12458724
3 Dias, S., et al. Evidence Synthesis for Decision Making 3. Medical Decision Making, 2013:33(5), 618–640. https://doi.org/10.1177/0272989x13485157
4 Dias, S., et al. Evidence Synthesis for Decision Making 4. Medical Decision Making, 2013:33(5), 641–656. https://doi.org/10.1177/0272989x12455847
5 Meta-Analyses of Randomized Controlled Clinical Trials to Evaluate the Safety of Human Drugs or Biological Products: Draft Guidance for Industry. U.S. Department of Health and Human Services, Food and Drug Administration. November 2018. Accessed April 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/meta-analyses-randomized-controlled-clinical-trials-evaluate-safety-human-drugs-or-biological
6 Depressive disorder (depression). World Health Organization. Accessed November 2025. https://www.who.int/news-room/fact-sheets/detail/depression
7 Key substance use and mental health indicators in the United States: Results from the 2023 National Survey on Drug Use and Health. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. Accessed November 2025. https://www.samhsa.gov/data/sites/default/files/reports/rpt47095/National%20Report/National%20Report/2023-nsduh-annual-national.pdf
8 Su YA and Si T. Progress and challenges in research of the mechanisms of anhedonia in major depressive disorder. Gen Psychiatr. 2022;35:e100724. doi:10.1136/gpsych-2021-100724
9 Pandya M, et al. Where in the Brain Is Depression? Curr Psychiatry Rep. 2012;14:634–642. doi:10.1007/s11920-012-0322-7
10 Bhagwagar Z. Remission With Lumateperone 42 mg Adjunctive to Antidepressant Therapy in Patients With Major Depressive Disorder: Analysis of Short-Term and Long-Term Trials. American College of Neuropsychopharmacology Annual Meeting; January 12-15, 2026. Poster TH66.
11 Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi:10.1176/ajp.2006.163
12 Zhu L et al. Economic burden and antidepressant treatment patterns among patients with major depressive disorder in the United States. J Manag Care Spec Pharm. 2022;28(11-a suppl):S2–S13. doi:10.18553/jmcp.2022.28.11-a.s
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