Treatment Resistant Depression (Pilot)
Condition: Depressive Disorder, Treatment-Resistant
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Study type: Interventional

Summary: 
      Treatment resistant depression (TRD) is a major public health problem. Current therapeutic
      options for this patient population remain limited. With all available treatments, only a
      sub-set of those patients who achieve an antidepressant response are likely to achieve
      treatment-induced remission. The need for antidepressant medication that can provide both
      rapid and long lasting relief of TRD symptoms is widely recognized. There is new evidence
      that drugs that block NMDA glutamate receptors (NMDA antagonists) are promising candidates
      for meeting this need. Existing studies in TRD have used only a low-dose, brief infusion of
      ketamine that would not be expected to re-sensitize the NMDA receptor; in agreement with this
      theory, these prior studies have found only temporary improvements of depression. Our key
      hypothesis is that a higher-dose, longer-term ketamine infusion, such as that used in chronic
      pain studies, would provide a more robust and lasting improvement from depression.

      Accordingly, we will test whether a 100-hour ketamine infusion would be more effective than
      the standard 40-minute ketamine infusion currently used in other TRD studies. We will
      randomize subjects to one of 2 arms: (1) 100-hour (+/- 4 hours) ketamine infusion plus
      clonidine for the entire infusion (2) 40-minute ketamine infusion (plus clonidine) following
      a 100+/- hour saline infusion. All subjects will receive clonidine, an alpha-2 agonist, to
      minimize side effects of ketamine (namely, brief/mild psychotic and cognitive symptoms).
    

Detailed description: 
      This experiment is a pilot study involving up to 20 healthy males or females between the ages
      of 18-65 to test whether a 100-hour ketamine infusion plus clonidine would be more effective,
      with longer lasting results, then the standard 40-minute ketamine infusion (plus clonidine).
      Each of the 2 arms, will be evaluated using a between subject, double-blind, randomized
      design.

        1. a. Controlled up to 100-hour IV ketamine infusion b. clonidine safener PO prior to
           infusion

        2. a. Controlled 40-minute IV ketamine infusion b. clonidine safener PO prior to infusion
           c. up to 100-hour(+/-)IV placebo (saline) infusion

        3. a. Controlled up to 100-hour IV ketamine infusion b. clonidine safener PO prior to
           infusion

        4. a.Controlled up to 100-hour IV ketamine infusion b. clonidine safener PO prior to
           infusion

      In both conditions, participants will be admitted to the Washington University School of
      Medicine Clinical Research Unit at Barnes-Jewish Hospital for approximately 108-hours (Monday
      morning-Friday evening). Pulse, blood pressure, pulse-oximetry, and an electrocardiogram
      strip will be routinely monitored. Serial labs and clinical/safety ratings will be done pre-,
      during, and post-infusion, with the last assessments being used to assure that subjects have
      returned to their "baseline" prior to discharge from the research unit. Participants will
      continue to see their primary psychiatrist throughout the study.
    

Intervention name(s): Ketamine; Clonidine; placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Controlled IV ketamine infusion (0.00225mg/kg-min. [18% (0.0125 mg/kg-min.).; Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion.; IV saline (i.e. placebo ketamine)
Other intervention name(s): Ketalar; Ketalin; Ketalor; Catapares; saline
Intervention MeSH terms: Clonidine; Ketamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: depression