Efficacy of Repeated Ketamine Infusions for Treatment-resistant Depression
Condition: Treatment-resistant Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Intervention: ketamine; midazolam
Intervention description: sedative; sedative
Intervention MeSH terms: Midazolam; Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 62.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Depressive Disorder, Treatment-Resistant

Summary:

      About one-third of depressed patients will not get better after multiple antidepressant
      treatments. This situation put a high burden on patients with depression due to worsening
      quality of life and increasing health care costs. Difficult-to-treat depression might be even
      worse among Veterans given that the frequency of depressive symptoms is 2 to 5 times higher
      than among the general US population. A breakthrough discovery happened in recent years when
      investigators found that one infusion from an old anesthetic named ketamine showed high
      efficacy and rapid antidepressant effect (sometimes within hours) but lasted only up to a
      week. The investigators propose to study if multiple infusions of ketamine can provide
      greater and longer antidepressant effects than one infusion. If that is the case, multiple
      infusions could be an alternative to relieve depressive symptoms that do not response to
      multiple antidepressant drugs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female Veterans aged 18 to 75 years.

          -  Have a telephone in their home and able to hear telephone conversations.

          -  Must meet current DSM-IV criteria for major depressive disorder (MDD), single or
             recurrent, without psychotic features confirmed by depression subset of the Structured
             Clinical Interview-Clinical Trial for DSM-IV (SCID).

          -  Have score 32 on the Inventory of Depressive Symptomatology-Clinician Rated
             (IDS-C30)for severity of major depressive episode (MDE) at screening.

          -  Current major depressive episode resistant to treatment defined as failure to achieve
             improvement from at least 2 antidepressant trials of different pharmacological
             classes. Systematic evaluation of previous antidepressant trials will be assessed by
             the Antidepressant Treatment History Form (ATHF) .

          -  If applicable, current antidepressant dosages including augmenting agents and/or
             frequency and duration of psychotherapy sessions must remain stable for at least 6
             weeks prior to beginning of the study.

        Exclusion Criteria:

          -  Inability to speak English.

          -  Inability or unwillingness to provide written informed consent.

          -  Moderate/severe cognitive impairment by Mini Mental State Examination (MMSE) scores
             27.

          -  Current or lifetime DSM-V criteria for post-traumatic stress disorder (PTSD), acute
             stress disorder, psychosis-related disorder, bipolar disorder I or II disorder,
             substance-induced mood disorder, any mood disorder due to a general medical condition
             or any Axis I disorder other than MDD as the primary presenting problem.

          -  History of moderate or severe traumatic brain injury, Parkinson's disease, dementia of
             any type, multiple sclerosis, seizures or other central nervous system (CNS) related
             disorders.

          -  History of comorbid substance disorder within 6 months of assessment plus positive
             urine toxicology screen test during baseline assessments.

          -  Clinically unstable medical illness that could compromise the patient's ability to
             tolerate or likely interfere with the study procedures (e.g., history of or current
             myocardial ischemia or arrhythmias, congestive heart failure, severe pulmonary, renal,
             or hepatic disease, uncontrolled hypertension).

          -  Current or within less than 14 days use of barbiturates or monoamine oxidase
             inhibitors (MAOi).

          -  For women: pregnancy (confirmed by lab test), initiation of female hormonal treatments
             within 3 months of screening, or inability/ unwillingness to use a medically accepted
             contraceptive method during the study.

          -  Imminent risk of suicidal/homicidal ideation and/or behavior with intent and/or plan.