Study to Treat Major Depressive Disorder (MDD) With a New Medication
Condition: Major Depressive Disorder; Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major
Intervention: ezogabine
Intervention description: Treatment Week 1: 100mg of Ezogabine by mouth three times per day (total daily dose = 300mg) Treatment Week 2: dose will be increased to 150 mg Ezogabine by mouth three times per day (total daily dose = 450mg).
Treatment Week 3: dose will be increased to 200mg of Ezogabine by mouth three times per day (total daily dose = 600mg).
Treatment Week 4: dose will be increased to 250mg of Ezogabine by mouth three times per day (total daily dose = 750mg).
Treatment Week 5: dose will be increased to 300mg of Ezogabine by mouth three times per (total daily dose = 900mg).
Participants will continue to take 900mg of Ezogabine per day and return weekly to the clinic for the remainder of the study.
Following this primary outcome visit, participants will be instructed to taper the study medication over the following 3 weeks based on FDA recommended guidelines as follows:
250 mg po TID daily x 1 week, then 200 mg po daily x 1 week, then 100 mg po daily x 1 week, then discontinue
Intervention MeSH terms: Ezogabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: major depressive disorder; depression; treatment resistent depression

Summary:

      The purpose of this study is to test the antidepressant effects of Ezogabine in major
      depressive disorder (MDD). The investigators also aim to determine the safety and
      tolerability Ezogabine in patients with MDD. The investigators hypothesize that depressive
      symptoms will be significantly decreased following an 8-week treatment period of the
      medication compared to baseline.
    

Eligibility criteria:

        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.