The goal of this clinical trial is to test the efficacy of lactate (a natural substance) in combination with standard antidepressant treatment, in patients hospitalized for a major depressive episode.

The main question[s] it aims to answer are:

• does lactate diminishes depression severity when administered in combination with antidepressant ?
• is it feasible to test lactate treatment in a large-scale clinical trial ? Participants will receive lactate intravenously daily (20 min infusion) for 5 days during hospitalisation (together with the standard antidepressant treatment).

Researchers will compare with a group receiving a placebo instead of lactate to see if lactate has antidepressant effects.

In case of major depressive disorder (MDD), antidepressant medications are prescribed as standard treatment. The commonly used antidepressants have a delayed onset of therapeutic actions, many side effects and limited efficacy. In this regard, about 30-50% of MDD patients are unresponsive to any currently approved pharmacological treatment, emphasizing the need for novel types of drugs to treat major depression.

Several animal studies have shown that lactate, a substance naturally present in the body, has antidepressant effects.

The aim of this single-center study is to evaluate the feasibility of conducting a future large-scale clinical trial testing the efficacy of "sodium lactate" as an adjunctive treatment to a standardly prescribed antidepressant.

The study is recruiting patients hospitalized for a major depressive episode. Participants are assigned randomly to the "sodium lactate" group or the "placebo" group. The study treatment will be administered intravenously daily (2mmol/kg) for 5 days during hospitalization, in addition to standard antidepressant treatment. Patients will be followed during hospitalization and then on an outpatient basis at 6 and 12 weeks. The therapeutic effect of sodium lactate will be assessed with the MADRS score (depression severity scale) at 1, 2, 3, 6 and 12 weeks. Recruitment, adherence, retention, data completion and blinding maintenance rates will also be assessed to evaluate the feasibility. The effect on anxiety, perceived stress, insomnia, short-term depression remission rate, blood lactate level and length of hospitalization will also be evaluated.

Inclusion Criteria:

• Study consent signed
• 18 ≤ age ≤ 65 years old
• Fluent in french
• Recently (no more than 1 week) hospitalized for a primary diagnosis of MDD
• Current major depressive episode as defined by DSM-5
• Current MADRS score ≥18
• Total number of MDD acute episodes ≤ 3
• Total number of psychiatric medications ≤ 3 at admission
• Total number of any medication ≤ 4 at admission
• No signs or evidence indicating difficult intravenous access
• Willing to hold a peripheral blood catheter for 5 days

Exclusion Criteria:

• Bipolar depression

• History of panic attacks

• Severe substance use disorders according to DSM-5-TR criteria

• Conditions predisposing to hypernatremia such as:

  • adrenocortical insufficiency,
  • diabetes type 1 and insulin-dependent type 2
  • extensive tissue injury

• Known severe renal insufficiency

• Known hepatic insufficiency (impaired lactate metabolism)

• Known history of heart failure

• Known history of Chronnic Obstructive Pulmonary Disease or respiratory failure

• Known hypersentitivity to lactate

• Hypernatremia with Na+ > 150 mmol/L (confirmed on 2 blood withdrawals)

• Blood osmolality > 320 mmol/kg H2O

• Hyperlactatemia > 2 mmol/l

• Pregnant or lactating

• Forbiden medications : Lithium

• Participation to other clinical trials

• Any medical conditions that could jeopardize patient's health in case of study participation according to the investigator

• Inability to give informed consent (without capacity for discernment) as evaluated by the psychiatrist investigator or by by a delegated physician.