Evaluation of Hypothalamic Phospholipids and Citalopram Hydrobromide in Enhancing Antidepressant Response in Elderly Patients with Major Depressive Disorder

The primary objective of this clinical trial is to evaluate whether **Liposom Forte** enhances the response to antidepressant therapy with citalopram in elderly patients diagnosed with Major Depressive Disorder (MDD). This is clinically relevant as it may offer a more effective treatment strategy for this population, potentially improving therapeutic outcomes and quality of life.

Secondary objectives include:

• Determining if Liposom Forte accelerates the response to antidepressant therapy with citalopram.
• Assessing the Clinical Global Impression of treatments.
• Evaluating the safety of the study treatments.

The clinical trial involves participants diagnosed with **Major Depressive Disorder** in elderly patients. The study population includes both male and female subjects aged 65 years and older. Participants are required to meet specific criteria, such as a score of 16 or higher on the Hamilton Depression Rating Scale (HAM-D) and a score of 23 or higher on the Mini-Mental State Exam (MMSE-2). They must also be capable of understanding the study procedures and complying with protocol requirements, as well as legally able to provide written informed consent. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the safety and effectiveness of Liposom Forte in enhancing and accelerating the response to antidepressant therapy with citalopram in elderly patients diagnosed with **Major Depressive Disorder** (MDD). The trial will be conducted over a period of approximately six years, with an estimated end date of December 31, 2025. Participants will be randomly assigned to receive either Liposom Forte, citalopram, or a placebo, with the primary objective being the improvement of depressive symptoms as measured by the Hamilton Rating Scale for Depression (HAM-D) at various intervals throughout the study.

The study will include several key visits: an initial **screening visit** to confirm eligibility based on criteria such as age (≥ 65 years), DSM-V criteria for MDD, and cognitive function scores. Following the screening, participants will undergo a series of follow-up visits at specified intervals (Visit 2, Visit 3, Visit 4, and Visit 5) to assess the primary and secondary endpoints, including changes in depressive symptoms, percentage of responders, and reduction in latency time to response. The **end-of-study visit** will occur at Visit 8 (Day 90), where final assessments will be conducted, including safety evaluations through adverse event tracking, ECG, and vital signs measurements.

Participant involvement is expected to last up to 90 days, with conditions for early termination including non-compliance with study procedures, withdrawal of consent, or adverse events that compromise participant safety. The trial will adhere to rigorous methodological standards to ensure the reliability and validity of the findings, contributing valuable insights into the treatment of MDD in the elderly population.

The clinical trial involves the administration of **LIPOSOM FORTE**, a solution for injection containing **hypothalamic phospholipids** as the active substance. This investigational product is provided in a concentration of 28 mg/2 ml and is administered via **intramuscular use**. The maximum daily dose is 56 mg, with a total maximum dose of 1680 mg over a treatment period of 30 days. The product is manufactured by FIDIA FARMACEUTICI S.P.A and is classified under the ATC code N07XX, indicating its categorization as an "Other Nervous System Drug." Participant compliance with the dosing schedule will be monitored throughout the trial.

In addition to the experimental treatment, the study includes the administration of **Citalopram Aurobindo**, a film-coated tablet containing **citalopram hydrobromide**. This medication is administered orally, with a maximum daily dose of 10 mg and a total maximum dose of 900 mg over a 90-day treatment period. Citalopram is a well-established antidepressant, classified under the ATC code N06AB04. The product is manufactured by AUROBINDO PHARMA (ITALIA) S.R.L. and serves as a standard-of-care therapy in this trial.

A **placebo** of Liposom Forte is also utilized in this study to maintain the double-blind design. The placebo is intended to mimic the experimental treatment without containing any active substance. The administration route and dosing schedule for the placebo are designed to match those of the Liposom Forte to ensure blinding integrity. Participant adherence to the placebo regimen will be monitored in the same manner as the active treatments.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints, focusing on the improvement of depressive symptoms in elderly patients with **Major Depressive Disorder (MDD)**. The primary endpoint involves evaluating the change in depressive symptoms from baseline to Visit 5 (day 30) using the Hamilton Rating Scale for Depression (21-item HAM-D). This scale is a validated tool commonly used to measure the severity of depression.

Secondary endpoints include several measures: the overall improvement of depressive symptoms throughout the study using the HAM-D, the percentage of patients classified as responders at Visits 2, 3, 4, and 5, defined as those achieving a ≥ 50% improvement in HAM-D score from baseline. Additionally, the reduction in latency time to response, defined as the time from baseline to achieving a ≥ 50% improvement in HAM-D score, will be assessed at the same visits. The Geriatric Depression Scale (GDS-15) will be used to evaluate changes in depressive symptoms from baseline at each visit, up to Visit 8 (Day 90). The Clinical Global Impression (CGI) score will also be used to assess changes from baseline at each visit, up to Visit 8.

Data collection will occur at specified timepoints, with efficacy assessments conducted at each visit. The trial will also monitor the safety of the study treatments by tracking adverse events, electrocardiogram (ECG) results, and vital signs at each visit, up to Visit 8 (Day 90). These comprehensive assessments will provide a robust evaluation of the efficacy and safety of the investigational treatment in enhancing the response to antidepressant therapy with citalopram in the target population.