Study to Treat Major Depressive Disorder With a New Medication
Condition: Depressive Disorder; Anhedonia
MeSH terms: Anhedonia; Depressive Disorder; Depression
Intervention: Ezogabine; Placebos
Intervention description: daily for 5 weeks; placebo pill daily for 5 weeks
Intervention MeSH terms: Ezogabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: Double blind
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: depression; anhedonia; reward

Summary:

      This project is designed to examine the neuronal KCNQ2/3 potassium (K+) channel subtype as a
      novel treatment target for mood disorders through the administration of the KCNQ-selective
      channel opener ezogabine (Potiga, GlaxoSmithKline; FDA-approved for the treatment of seizure
      disorders).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent obtained from subject and ability for subject to comply with
             the requirements of the study;

          -  Men and women, age 18-65;

          -  Participants must meet DSM-V criteria for current depressive disorder (major
             depressive disorder [MDD], persistent depressive disorder, other specified depressive
             disorder) as determined by a study psychiatrist and confirmed using the Structured
             Clinical Interview for DSM-V (SCID);

          -  Clinically significant anhedonia as determined by a SHAPS score ≥ 20 at screening;

          -  Current illness severity is at least moderate, defined as a score of ≥4 on the
             Clinical Global Impression-Severity (CGI-S) Scale;

          -  If female of childbearing potential, must agree to use of a medically accepted form of
             contraception, or else agree to abstinence.

        Exclusion Criteria:

          -  A primary psychiatric diagnosis other than a depressive disorder as defined by DSM-V
             [co-morbid anxiety disorders (including agoraphobia, generalized anxiety disorder,
             social anxiety disorder and panic disorder) and Posttraumatic Stress Disorder (PTSD)
             are allowed] or major cognitive disorder;

          -  Meets criteria for a substance or alcohol use disorder in the past 6 months;

          -  Female participants who are pregnant, breastfeeding, or may become pregnant, or
             unwilling to practice birth control during participation in the study;

          -  Positive urine toxicology screen for drugs of abuse at the time of screening;

          -  Any unstable medical illnesses including hepatic, renal, gastroenterologic,
             respiratory, cardiovascular (including ischemic heart disease), endocrinologic,
             neurologic, immunologic, or hematologic disease;

          -  Clinically significant abnormalities of laboratory tests, physical examination, or
             ECG;

          -  Prolonged QT Interval at screening, operationalized as a QTc of > 480 ms;

          -  A history of retinal abnormalities (i.e., pigment changes, retinal dystrophy) or
             findings of retinal pathology on ophthalmological exam at baseline;

          -  Presence of a condition or abnormality that in the opinion of the Investigator would
             compromise the safety of the patient or the quality of the data;

          -  Use of any dis-allowed medication according to the study protocol;

          -  Serious and imminent risk of self harm or violence as determined by the PI;

          -  Extreme illness severity as defined by a GCI-S score >6;

          -  Any contraindication to MRI including 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;

          -  History of non-response to electroconvulsive therapy in the current depressive episode

               -  Exceptions:

                    1. Subjects with a positive urine drug screen for cannabinoids, barbiturates,
                       opiates, amphetamines, or benzodiazepines may be allowed in the study
                       provided that the drug was used for a documented, legitimate medical purpose
                       and/or the use of such products may be discontinued (documented by a
                       negative repeat test) prior to randomization;

                    2. Medically appropriate episodic use (up to 3 days) of narcotic analgesics for
                       acute medical indications is allowed (Discussion with PI required)

                         -  Potential participants will not be discontinued from medication for the
                            purposes of this study. If a patient is taking a protocol dis-allowed
                            medication at the time of screening, the patient may discontinue the
                            medication under the supervision of the treating physician in the case
                            that the patient is not benefiting from the medication or otherwise
                            wishes to discontinue the medication. In no case will a dis-allowed
                            medication be discontinued for the purpose of study participation if
                            the patient is receiving clinical benefit from the medication.