Evaluation of the Efficacy, Safety, and Tolerability of Lacosamide in Major Depressive Episodes of Bipolar Disorder Types I and II.

Evaluation of the Efficacy, Safety, and Tolerability of Lacosamide in Major Depressive Episodes of Bipolar Disorder Types I and II: a Randomized, Controlled, Double-blind, Parallel-group Clinical Trial.

Initially, observational studies suggested a possible effect of Lacosamide on depressive and anxious symptoms in individuals with epilepsy, and later, an open-label study demonstrated the efficacy of lacosamide in improving depressive and manic symptoms in individuals with bipolar disorder (BD). The primary objective of this study is to evaluate the efficacy of combining lacosamide as an augmentation treatment to first- or second-line medication treatments in moderate to severe major depressive episodes of treatment-resistant BD I and II (failure of at least two adequate treatments during the current episode). The main hypothesis of the study is that lacosamide produces a greater reduction in depression scores compared to a placebo treatment and that both groups will exhibit similar rates of side effects and adverse events. We will conduct a double-blind, randomized, parallel-group pilot study, comparing the enhancement of the treatment that patients had been using with lacosamide and placebo, over a duration of 12 weeks. Forty subjects aged between 18 and 65 years with a diagnosis of BD (I or II) in a moderate or severe major depressive episode, despite the use of first- or second-line treatments, will be selected. The primary outcome will be the assessment of lacosamide efficacy through the difference in scores on the Hamilton Depression Rating Scale (HAMD-17) from the initial visit to the end of week 12 of intervention between the lacosamide and placebo groups.

Study Overview

• Status: Recruiting
• Conditions: Bipolar Affective Disorder
• Intervention / Treatment: Drug: Lacosamide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ricardo Alberto Moreno, Professor; Phone Number: +55 11 2661-6648; Email: grudaipq@hc.fm.usp.br

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil
      • Recruiting
      • Instituto de Psiquiatia (IPQ)
      • Contact: Phone Number: +55 (11) 2661-6648; Email: grudaipq@hc.fm.usp.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of bipolar disorder (type I or II) confirmed by structured clinical interview;
2. acute major depressive episode of moderate or severe intensity;
3. no response to at least two adequate pharmacological interventions to treat the current episode.

Exclusion Criteria:

1. Current diagnosis of schizophrenia, dementia, intellectual disability, organic mental disorder (by clinical assessment). Comorbidity with other psychiatric disorders (personality disorders, anxiety disorders, substance use disorders, eating disorders, and attention deficit disorder) will be permitted provided the primary diagnosis is bipolar disorder;
2. acute suicidal ideation (defined by HAMD-17 item 3 ≥ 3 points or by clinical assessment);
3. current depressive episode with psychotic features (by clinical assessment);
4. suspected or confirmed pregnancy;
5. severe or unstable clinical illnesses;
6. previous history of non-response to an adequate course of at least 8 sessions of electroconvulsive therapy;
7. previous history of non-response to an adequate course of ketamine treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Group	Drug: Placebo; Placebo tablets are similar in its features to the active drug, but without any pharmacological agent inside.
Experimental: Active Group; Lacosamide 50mg twice a day	Drug: Lacosamide; Lacosamide 50mg will be give twice a day por 2 weeks, then Lacosamide 100mg twice a day until the end of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary outcome	The efficacy of lacosamide assessed by the difference in Hamilton Depression Scale score from the initial visit to the end of week 12 of the intervention between the lacosamide and placebo groups. Minimum: 0 point Maximum: 50 points. The increase in the pontuation of the scale is related to worse outcomes.	week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary outcome	Difference in side effects from the initial visit to the end of week 12 of intervention, between the lacosamide and placebo groups;	week 12
Secondary Outcome	Difference in response rates (50% or more reduction) assessed by the Hamilton Depression Scale from the initial visit to the end of week 12 of intervention, between the lacosamide and placebo groups;	week 12
Secondary outcome	Difference in response rates (50% or more reduction) assessed by the Montgomery-Asberg Depression Rate Scale from the initial visit to the end of week 12 of intervention, between the lacosamide and placebo groups;	week 12
Secondary outcome	Difference in remission rates (< 7 points) assessed by the Hamilton Depression Scale from the initial visit to the end of week 12 of intervention, between the lacosamide and placebo groups;	week 12
Secondary outcome	Difference in remission rates (<11 points) assessed by the Montgomery-Asberg Depression Rate Scale from the initial visit to the end of week 12 of intervention, between the lacosamide and placebo groups;	week 12

Collaborators and Investigators

• Sponsor: University of Sao Paulo
• Collaborators: Libbs Farmacêutica LTDA

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: February 6, 2026
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: bipolar disorder; randomized clinical trial; lacosamide; bipolar depression
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Mood Disorders; Bipolar Disorder; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Amides; Acetamides; Acetates; Lacosamide
• Other Study ID Numbers: Lacosamide on bipolar disorder

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No