Ketamine Plus Lithium in Treatment-Resistant Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Intervention: Lithium; Ketamine; Placebo
Intervention description: Subjects in this arm take 600-1200mg of Lithium pills at night for duration of the study.; Subjects in this arm take placebo pills at night for duration of the study.
Intervention MeSH terms: Ketamine; Lithium Carbonate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 34.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Ketamine; glutamate; N-methyl-D-aspartate; depression; major depressive disorder; treatment resistant; antidepressant; lithium

Summary:

      The purpose of this study is to test the antidepressant effect of ketamine when given
      repeatedly over a period of 1 week, as well as the use of Lithium as a relapse-prevention
      strategy for patients with treatment-resistant depression (TRD) who respond to an initial
      series of ketamine infusions. Ketamine is a Food and Drug Administration approved anesthetic
      (a drug used to produce loss of consciousness before and during surgery). Ketamine is not
      approved for the treatment of major depressive disorder and is considered experimental in
      this study. An additional purpose of this study is to research the effects of ketamine on
      brain function.

      You may qualify to take part in this research study because you have been diagnosed with
      major depressive disorder (MDD) and have not responded to past treatments.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients, 21-65 years of age;

          -  Female individuals who are not of childbearing potential (i.e., surgically sterile,
             postmenopausal for at least one year) or using a medically accepted reliable means of
             contraception. Women using oral contraceptive medication for birth control must also
             be using a barrier contraceptive. Women of childbearing potential must also have a
             negative serum B-HCG at screening and at pre-infusion;

          -  Participants must fulfill DSM-IV criteria for Major Depression without psychotic
             features, based on clinical assessment by a study psychiatrist and confirmed by a
             structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis
             I Disorders, Patient Edition (SCID-P);

          -  Participants must have a history of at least one previous episode of depression prior
             to the current episode (recurrent MDD) or have chronic MDD (of at least two years'
             duration);

          -  Participants have not responded to two or more adequate trials of an antidepressant as
             determined by Antidepressant Treatment History Form (ATHF) criteria (score >=3);

          -  Current Major Depressive Episode of at least moderate severity, defined as a QIDS-SR
             score ≥ 14 and a CGI-S score of ≥ 4;Current major depressive episode is of at least 4
             weeks duration;

          -  Each participant must have a level of understanding sufficient to agree to all tests
             and examinations required by the protocol and must sign an informed consent document;

          -  Each participant must be able to identify a family member, physician, or friend who
             will participate in the Treatment Contract.

        Exclusion Criteria:

          -  Lifetime history of psychotic features, diagnosis of schizophrenia or any other
             psychotic disorder, or diagnosis of bipolar disorder;

          -  Lifetime histories of autism, mental retardation, pervasive developmental disorders,
             or Tourette's syndrome;

          -  Current diagnosis of OCD or eating disorder (bulimia nervosa or anorexia nervosa);

          -  Subjects with DSM-IV drug or alcohol abuse/dependence within the preceding 2 years;

          -  Patients with schizotypal or antisocial personality disorder, or any clinically
             significant axis II disorder that would, in the investigator's judgment, preclude safe
             study participation;

          -  Patients judged clinically to be at serious and imminent suicidal or homicidal risk;

          -  Women who are either pregnant or nursing;

          -  Serious, unstable medical illnesses including hepatic, renal impairment,
             gastroenterologic (including gastro-esophageal reflux disease), respiratory (including
             obstructive sleep apnea, or history of difficulty with airway management during
             previous anesthetics), cardiovascular (including ischemic heart disease and
             uncontrolled hypertension), endocrinologic, neurologic (including history of severe
             head injury), immunologic, or hematologic disease;

          -  Clinically significant abnormal findings of laboratory parameters, physical
             examination, or ECG;

          -  Patients who have a positive urine toxicology for illicit substances at screening and
             within 24 hours of the infusion;

          -  Patients with one or more seizures without a clear and resolved etiology;

          -  Treatment with an irreversible MAOI within 2 weeks prior to randomization or
             fluoxetine within 4 weeks prior to randomization;

          -  Treatment with other antidepressants within one week of randomization;

          -  Previous recreational use of PCP or ketamine;

          -  Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg) not controlled by
             diuretic or beta-blocker therapy alone or in combination;

          -  A blood pressure reading over 160/90 or two separate readings over 140/90 at screening
             or baseline visits;

          -  Renal impairment, as reflected by a BUN > 20 mg/dL and/or creatinin clearance of >1.3
             mg/dL;

          -  Thyroid impairment, as reflected by a TSH > 4.2 mU/L;

          -  Cardiac disease, as reflected by an EKG that is abnormal and of concern for cardiac
             disease;

          -  Any anticipated change in medications that could affect fluid or salt balance,
             including the following antihypertensive agents: ACE inhibitor, loop diuretics,
             calcium channel blockers, thiazide diuretics, angiotensin II receptor blockers.