feasibility of conducting a clinical trial assessing efficacy of lactate as adjunctive therapy in patients with major depressive disorder

Conditions: Major Depressive Disorder

Summary: 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.

Eligibility criteria:
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.

Keywords: sodium lactate depression antidepressant lactate