Comparison of the Efficacy of Lacosamide versus Valproate in the Treatment of Acute Mania in Bipolar Disorder

Comparison of the Efficacy of Lacosamide versus Sodium Valproate in Patients with Bipolar I Disorder in the Acute Manic Phase

A Phase 3, randomized, double-blind, placebo-controlled, parallel-group clinical trial in 80 patients with bipolar I disorder in the acute manic phase. Randomization will be performed using balanced blocks with block sizes of 4 and 6. A total of 8 blocks of size 4 and 8 blocks of size 6 are planned for patient allocation.

The study will be conducted at Ibn Sina Psychiatric Hospital. Assessments will be performed at baseline (Day 0), as well as on Days 3, 7, and 14. Both patients and clinical raters will remain blinded to treatment allocation.

Inclusion Criteria: Definitive diagnosis of bipolar I disorder in the acute manic phase (according to DSM-5 criteria) Age 18–75 years (both sexes) YMRS score ≥ 20 at baseline evaluation Ability to undergo clinical assessments Provision of informed consent for participation Non-entry criteria: Pregnancy or lactation Intellectual disability or severe cognitive/functional impairment Predominant comorbid psychiatric disorder Hepatic impairment (ALT/AST > 3× ULN) Thrombocytopenia (platelet count < 100,000/μL) Use of amphetamine-type substances Second- or third-degree heart block History of hypersensitivity to lacosamide or valproate

Lacosamide Group: Treatment is initiated at a starting dose of 50 mg/day and gradually titrated up to 200–300 mg/day. Valproate Group: Treatment is initiated at a dose of 200 mg three times daily (i.e., 600 mg/day) and titrated over 2 weeks to reach a target dose of 20 mg/kg/day. Both groups will receive standard-of-care treatment for the acute manic phase.

Clinical response rate will be assessed using the CGI and YMRS scales after two weeks of treatment.

The randomization method is designed using balanced blocks with block sizes of 4 and 6. A total of 8 blocks of size 4 and 8 blocks of size 6 are planned for patient allocation. Randomization will be performed using a block design with variable block sizes to assign participants to the intervention and control groups. To ensure allocation concealment, the randomization process will be conducted using Random Allocation Software, version 2.0. Accordingly, after obtaining informed consent and confirming eligibility criteria, the researcher will enter the patient's initial identification data into the software, and the treatment group will be assigned instantly and automatically. This method eliminates any possibility of predicting group assignment and provides the highest level of blinding for the study.

This study is designed as a double-blind trial, meaning that both the participants and the study personnel responsible for drug allocation will be unaware of the treatment assignments. To maintain blinding, the study medications will be prepared and dispensed to patients by nurses independent of the study team, using identical, coded packaging (designated as A/B).

A de-identified individual participant dataset including demographic information, cognitive performance scores, behavioral and neuropsychiatric symptom scores, and recorded adverse events collected during the trial. All personal identifiers will be removed to ensure full anonymization. The dataset includes only variables used for analysis of primary and secondary outcomes. The data file will be provided in an encrypted format and structured in a standardized manner.

Access to the de-identified dataset will begin six months after publication of the main study results and will remain available for at least five years following the publication date.

Researchers affiliated with universities, medical research centers, or recognized scientific institutions who have an approved research proposal related to the study topic may request access. Applicants must demonstrate relevant research experience.

The data may be used exclusively for research purposes, secondary scientific analyses, or replication of study findings. Use of the data for commercial purposes or any attempt to re-identify participants is prohibited. Applicants must provide a detailed research proposal, a confidentiality agreement, and a formal commitment not to attempt participant re-identification. Any secondary publication must cite the original dataset source.

Requesters can send their application along with a brief proposal in Persian or English to the official email address of the Principal Investigator at [ManteghiA@mums.ac.ir]. The requester's name and institutional affiliation must be clearly stated.

Upon receiving a request, an initial review will be completed within five working days. If the research topic is appropriate, the applicant will be asked to submit a research proposal, a data confidentiality agreement, and a commitment not to attempt participant re- identification. After verification of all documents, the encrypted dataset will be shared within 10 to 15 working days. The entire process typically takes between two to four weeks