Lumateperone shows maintained symptom control and low metabolic risk over six months in bipolar depression
- **In a six-month open-label extension study of lumateperone for bipolar depression, 58.3% of patients completed the trial while mean Montgomery-Åsberg Depression Rating Scale scores decreased by 8.9 points from baseline.
- A total of 127 patients enrolled in the open-label extension period, with 74 patients (58.3%) completing the study.
- Treatment-emergent adverse events occurred in 73 patients (57.5%), and 54 patients (42.5%) experienced a drug-related treatment-emergent adverse event.
- Adverse events occurring in at least 5% of patients included headache, dry mouth, dizziness, nausea, somnolence, anxiety, and irritability.
The publication
**In a six-month open-label extension study of lumateperone for bipolar depression, 58.3% of patients completed the trial while mean Montgomery-Åsberg Depression Rating Scale scores decreased by 8.9 points from baseline. The treatment was generally well tolerated with minimal changes in cardiometabolic parameters and rare extrapyramidal symptoms.**
Who the findings apply to
Patients aged 18 to 75 years with a clinical diagnosis of bipolar I or II disorder experiencing a major depressive episode were eligible. Eligibility required a Montgomery-Åsberg Depression Rating Scale Total score of at least 20 and a Clinical Global Impression Scale-Bipolar Version, Severity score of at least 4.
Why this matters
The study addresses the need for long-term safety data on lumateperone, an antipsychotic approved for bipolar depression that modulates serotonin, dopamine, and glutamate. While earlier Phase 3 trials established short-term efficacy, this open-label extension provides evidence on tolerability and symptom maintenance over a longer duration.
What the study found
A total of 127 patients enrolled in the open-label extension period, with 74 patients (58.3%) completing the study. Treatment-emergent adverse events occurred in 73 patients (57.5%), and 54 patients (42.5%) experienced a drug-related treatment-emergent adverse event.
Adverse events occurring in at least 5% of patients included headache, dry mouth, dizziness, nausea, somnolence, anxiety, and irritability. Most treatment-emergent adverse events were mild or moderate in severity, and extrapyramidal-symptom-related adverse events were rare.
Most patients with normal metabolic laboratory values at baseline remained normal during the treatment period. Mean changes in blood pressure, pulse rate, electrocardiogram, and body morphology were minimal.
Depression symptoms improved as measured by the mean change from baseline to Day 175 in Montgomery-Åsberg Depression Rating Scale Total score (-8.9) and Clinical Global Impression Scale-Bipolar Version, Severity Total score (-2.3).
What the result does not establish
This was an open-label extension study, meaning patients and investigators were not blinded to the treatment assignment, which can introduce bias in safety and efficacy assessments. The study population consisted of patients who had previously completed a double-blind period or were re-screened, potentially limiting generalizability to treatment-naive individuals.
Authors’ conclusion
“In patients with bipolar depression, long-term LUMA treatment was generally well tolerated with low risk of extrapyramidal symptoms, weight gain, and cardiometabolic effects. These data further support the safety, tolerability, and effectiveness of LUMA in patients with bipolar depression.”
Trial registration
| Registered title | Clinical Trial Evaluating ITI-007 (Lumateperone) as a Monotherapy for the Treatment of Bipolar Depression |
|---|---|
| Registry status | Phase 3, interventional, completed |
| Lead sponsor | Intra-Cellular Therapies, Inc. |
| Registered size | 554 participants — actual enrolment. The abstract reports: 127 patients |
| Where | 55 sites in 1 country (United States) |
| Registered primary outcome |
|
| Results on the registry | Posted Nov 2025 |
- Start: Dec 2015
- Primary completion: Jan 2019
- Completion: Jul 2019
- Paper published: Apr 2023
- Results posted: Nov 2025
ClinicalTrials.gov record as held by ENCLAI, last updated Oct 2025. The registry status may have changed since; the link shows the current record.
| Registered title | Clinical Trial Evaluating ITI-007 as an Adjunctive Therapy to Lithium or Valproate for the Treatment of Bipolar Depression |
|---|---|
| Registry status | Phase 3, interventional, completed |
| Lead sponsor | Intra-Cellular Therapies, Inc. |
| Registered size | 529 participants — actual enrolment. The abstract reports: 127 patients |
| Where | 71 sites in 5 countries (Bulgaria, Russia, Serbia, Ukraine, United States) |
| Registered primary outcome |
|
| Results on the registry | Posted May 2023 |
- Start: Mar 2016
- Completion: Jul 2020
- Primary completion: Jul 2020
- Paper published: Apr 2023
- Results posted: May 2023
ClinicalTrials.gov record as held by ENCLAI, last updated Apr 2023. The registry status may have changed since; the link shows the current record.
| Registered title | Lumateperone Monotherapy for the Treatment of Bipolar Depression Conducted Globally |
|---|---|
| Registry status | Phase 3, interventional, completed |
| Lead sponsor | Intra-Cellular Therapies, Inc. |
| Registered size | 381 participants — actual enrolment. The abstract reports: 127 patients |
| Where | 47 sites in 6 countries (Bulgaria, Colombia, Russia, Serbia, Ukraine, United States) |
| Registered primary outcome |
|
| Results on the registry | Posted Jun 2022 |
- Start: Nov 2017
- Completion: Mar 2019
- Primary completion: Mar 2019
- Results posted: Jun 2022
- Paper published: Apr 2023
ClinicalTrials.gov record as held by ENCLAI, last updated May 2022. The registry status may have changed since; the link shows the current record.
Study and sources
Long-Term Lumateperone Treatment in Bipolar Disorder: Six-Month Open-Label Extension Study
Randomised trial · Phase 3 · CNS spectrums · 2023-04-01
Sources and limitations
- PubMed record PMID 43010211 (PubMed / NLM · 2026-11-12)
- Trial registry NCT02600494 (ClinicalTrials.gov · 2026-11-12)
- Trial registry NCT02600507 (ClinicalTrials.gov · 2026-11-12)
- Trial registry NCT03249376 (ClinicalTrials.gov · 2026-11-12)
Related briefings
Follow ENCLAI News
Get new briefings in your news reader. No ENCLAI account needed.
The daily disease brief
One email a day: what changed in official disease reporting worldwide, with the source named for every number. Reported facts only — no forecasts and no interpretation.