This Study Aims to Compare the Efficacy and Safety of Lumateperone and Cariprazine in Patients With Bipolar I Depression Using Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression Bipolar Severity Scale (CGI-BP-S) and Recording Treatment Emergent Adverse Effects (LUCAR-BD)

Watim Medical & Dental College

Status and phase: Begins enrollment in 2 months; Phase 4

Conditions: Bipolar 1 Depression

Treatments: Drug: Cariprazine; Drug: Lumateperone

Study type: Interventional

Funder types: Other

Identifiers

NCT07676669

WM&DC/R&D (IERB) /2026/264 (Other Identifier)

WMDC-RCT-BD-2026-01

Details and patient eligibility

About

This study aims to compare the efficacy and safety of lumateperone and cariprazine as adjuncts in patients with depression associated with bipolar I using standardized efficacy assessment tools such as the Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression bipolar severity scale (CGI-BP-S) and recording treatment emergent adverse effect.

Participants will undergo baseline assessment on day 0 using these scales. Follow-up assessments using MADRS and CGI scales will be conducted at Day 15, Day 30 and Day 45. Safety analysis will be performed for all participants who receive at least one dose of study medication. Vitals and treatment-emergent adverse events (TEAEs) will be recorded at every visit

Full description

Bipolar I disorder is a chronic and recurrent psychiatric illness characterized by episodes of mania and depression that significantly impair functioning and quality of life. Bipolar depression is associated with substantial morbidity, increased risk of suicide, and reduced psychosocial functioning. Although mood stabilizers remain the cornerstone of treatment, many patients experience inadequate response to mood stabilizer monotherapy, necessitating the use of adjunctive pharmacological agents.

Cariprazine and lumateperone are newer antipsychotic agents that have demonstrated efficacy in the treatment of bipolar depression. Cariprazine is a dopamine D3/D2 receptor partial agonist with preferential affinity for D3 receptors, whereas lumateperone exhibits a unique mechanism involving modulation of dopaminergic, serotonergic, and glutamatergic neurotransmission. Despite evidence supporting the efficacy of both agents, direct comparative data regarding their effectiveness and safety as adjunctive therapy in Bipolar I depression remain limited.

This randomized controlled trial aims to compare the efficacy and safety of lumateperone and cariprazine as adjunctive therapy to ongoing mood stabilizer treatment in adults diagnosed with Bipolar I Disorder experiencing a current depressive episode. Eligible participants will be randomly assigned to receive either lumateperone or cariprazine in addition to their prescribed mood stabilizer for an 6-week treatment period.

The primary efficacy outcome will be the change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to Week 6. Secondary efficacy outcomes will include changes in Clinical Global Impression for Bipolar Disorder-Severity (CGI-BP-S) depression scores and assessment of treatment response and remission rates. Treatment response will be defined as a clinically significant reduction in depressive symptoms as measured by MADRS, while remission will be determined using established MADRS threshold criteria.

Safety and tolerability will be evaluated throughout the study through regular monitoring of vital signs, physical examinations, and the occurrence of treatment-emergent adverse events (TEAEs). All adverse events will be documented and assessed for severity and relationship to study medication.

The findings of this study are expected to provide comparative evidence regarding the effectiveness and safety of lumateperone and cariprazine as adjunctive treatment options for Bipolar I depression and may assist clinicians in making evidence-based treatment decisions for patients who demonstrate an inadequate response to mood stabilizer therapy alone.

Enrollment: 140 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients aged 18-60 years
• Diagnosed with bipolar I depression according to DSM-5 criteria
• On stable dose of mood stabilizer (lithium or valproate) for at least 2 weeks
• Moderate to severe depressive symptoms (baseline MADRS score ≥20)
• Willing to provide informed consent

Exclusion criteria

• • Current manic or mixed episode

  • Rapid cycling bipolar disorder
  • Substance use disorder
  • Severe neurological illness or medical emergency
  • Pregnancy or lactation
  • Treatment-resistant depression requiring ECT
  • Active suicidal risk requiring emergency intervention

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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140 participants in 2 patient groups

lumateperone plus mood stabilizer

Experimental group

Description:

Lumateperone administered as adjunctive therapy in addition to ongoing mood stabilizer treatment for bipolar I depressive episode

Treatment:

Drug: Lumateperone

Cariprazine plus mood stabilizer

Active Comparator group

Description:

Cariprazine administered as adjunctive therapy in addition to ongoing mood stabilizer treatment for bipolar I depressive episode.

Treatment:

Drug: Cariprazine