Study to Treat Major Depressive Disorder (MDD) With a New Medication

Inclusion Criteria

• Male or female participants, 18-65 years of age;
• Current diagnosis of major depressive disorder according as determined by a psychiatrist and confirmed with The Mini-International Neuropsychiatric Interview (MINI);
• At least moderate depression severity as defined by a score of >= 21 on the Montgomery-Asberg Depression Rating Scale (MADRS);
• At least a moderate level of anhedonia based on a Snaith-Hamilton Pleasure Scale (SHAPS) score ≥ 20;
• If female of childbearing potential, must agree to use of a medically accepted form of contraception, or else agree to abstinent;
• Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.

Exclusion Criteria

• Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder, obsessive compulsive disorder or pervasive developmental disorders or mental retardation;
• Diagnosis of a substance use disorder within the past 6 months (excluding substance use disorder in sustained remission)
• Female participants who are pregnant, nursing, for may become pregnant;
• Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
• Clinically significant abnormalities of laboratories, physical examination, or ECG;
• Prolonged QT Interval at screening, operationalized as a QTc of > 480 ms at baseline;
• Hypokalemia (potassium value less than 3.5mEq/L) or hypomagnesemia (magnesium value less than 1.6mEq/L) at baseline;
• A history of retinal abnormalities (ie, pigment changes, retinal dystrophy) or findings of retinal pathology on ophthalmological exam at baseline
• Antidepressant medication within 2 weeks of start of treatment (4 weeks for fluoxetine)*
• Other psychotropic medication, including antipsychotics and mood stabilizers within 2 weeks of start of treatment; subjects will be allowed to remain on a stable dose of zolpidem 10 mg nightly for sleep or a benzodiazepine as needed for sleep or anxiety (dosage equivalent to lorazepam 1 mg daily or less)
• No current or recent significantly elevated risk of self-harm or violence as determined by the PI.
• For subjects who may participate in the MRI portion of the study, claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more.