Intravenous Ketamine for Treatment-Resistant Depression

Peak (% change from baseline) Anterior Cingulate Cortex metabolites (Gamma-Aminobutyric Acid and Glutamate)

To measure peak (% change from baseline) Anterior Cingulate Cortex (ACC) Gamma-Aminobutyric Acid (GABA) and Glutamate (Glu) levels during a 40-minute IV ketamine or normal saline (0.9% sodium chloride) infusion utilizing fMRS (functional Magnetic Resonance Spectroscopy)

Change in peripheral Gamma-Aminobutyric Acid and Glutamate levels

Change in peripheral Gamma-Aminobutyric Acid (GABA) and Glutamate (Glu) levels measured utilizing liquid chromatography-mass spectrometry (LCMS) at baseline and the end of 40-minute infusion

Change in the Montgomery Asberg Depression Rating Scale

Montgomery Asberg Depression Rating Scale (MADRS) is a 10-item clinician rating of depressive symptoms used in the previous ketamine research studies. Higher scores represent higher levels of depression.

Correlation between the percent change in central (anterior cingulate cortex) Gamma-Aminobutyric Acid and Glutamate levels and the change in depression severity measured using the Montgomery-Åsberg Depression Rating Scale

Outcome measure: Changes in the total Montgomery-Asberg Depression Rating Scale (MADRS) scale from baseline (pre-infusion) to 24 hours post-infusion. MADRS will be compared by randomized arm as a continuous variable as well as defined by remission status (MADRS≤9). The total MADRS score can range from 0 to 60, with higher scores indicating a worse outcome. We aim to evaluate the correlation between the percent change in anterior cingulate cortex (ACC) Gamma-Aminobutyric Acid (GABA) and Glutamate (Glu) levels (from baseline to peak) during a 40-minute IV infusion of ketamine or normal saline (0.9% sodium chloride) using functional magnetic resonance spectroscopy (fMRS) and the change in MADRS scores (from baseline to 24 hours).

Change in McIntyre And Rosenblat Rapid Response Scale

The McIntyre and Rosenblat Rapid Response Scale (MARRRS) is a validated self-report instrument designed to assess rapid treatment response in the context of rapid-acting antidepressant drugs (RAADs), such as ketamine. The scale comprises 14 items and has shown promising psychometric properties, including high internal consistency and significant convergent validity. Each item is scored on a 4-point ordinal scale, where 0 indicates the absence of symptoms and 3 signifies the highest severity of symptoms. The total score ranges from 0 to 42, with higher scores indicating a more severe state of depression.

Change in Quick Inventory of Depressive Symptomatology (Self-Report)

The Quick Inventory of Depressive Symptomatology (QIDS-SR-16) is a depression scale that assesses the symptom domains of major depressive disorder, with scores ranging from 0 to 27. Higher scores indicate more severe depressive symptoms. The individual items evaluate key aspects such as sadness, anhedonia (the loss of pleasure), and sleep disturbances, which may manifest as insomnia or hypersomnia. Additionally, the scale addresses changes in appetite or weight and includes assessments of psychomotor agitation or retardation. It also measures fatigue or loss of energy, feelings of worthlessness or excessive guilt, and difficulties in concentration. Furthermore, the scale incorporates items related to suicidal ideation, offering a comprehensive overview of both the emotional and physical symptoms experienced by individuals with depression.

Changes in short chain acylcarnitine levels

Changes in short-chain acylcarnitine (AC) levels-early change (baseline to 40 minutes) and late change (100 minutes to 24 hours)-among patients who received a 40-minute IV infusion of either ketamine or normal saline (0.9% sodium chloride).

Changes in short-chain acylcarnitine levels and ketamine-related remission

To evaluate the relationship between changes in short-chain AC levels-early change (baseline to 40 minutes) and late change (100 minutes to 24 hours)-among remitters and non-remitters (MADRS \< 10) at 24 hours.