Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients
Condition: Treatment Resistant Depression
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary goal of the project is to study the effect of Ketamine on cortical
      neurophysiological function in TRD patients. The proposal employs robust and non-invasive
      neurophysiological techniques TMS and EEG to investigate the cortical excitability and
      oscillatory activity in patients with treatment resistant depression.
    

Detailed description: 
      The primary goal of the project is to study the effect of Ketamine on cortical
      neurophysiological function in Treatment Resistant Depression(TRD) patients. There are three
      key preclinical findings regarding Ketamine antidepressant effects that motivate the current
      study: a) low dose Ketamine causes early increase in glutamate neurotransmission; b) Ketamine
      initiates synaptic plasticity; c) ketamine infusion leads to rapid improvement in depression
      symptoms. The proposal essentially employs robust and non-invasive neurophysiological
      techniques, Auditory Steady State Response(ASSR)-gamma oscillatory response and Transcranial
      Magnetic Stimulation(TMS) cortical excitability to investigate the above findings in patients
      with treatment resistant depression.

      Study:

      Ketamine Infusion:

      We will employ an open-label study in which the infusion session, the enrolled TRD patients
      will receive low dose Ketamine (0.5 mg/kg) over 40 minutes.

      Cortical Excitability:

      TMS stimulation will be applied to the corresponding region of the contralateral primary
      motor cortex to determine motor threshold and to examine the motor cortical excitability
      measures after Ketamine. The optimal coil position will be determined by moving the TMS coil
      in 1-cm increments over the motor cortical area while delivering single or paired magnetic
      pulses and by observing maximal contraction of the contralateral abductor pollicis brevis
      (APB). Electromyography readings will be obtained from the APB muscle. TMS stimulation will
      then be applied to Left DLPFC or Left Brodmann Area 6 to investigate cortical excitability
      changes after ketamine. Electroencephalography(EEG) recordings will be concurrent with TMS
      procedure.

      ASSR/EEG paradigm:

      Participants may engage in the auditory steady state response task where click trains of
      500-ms duration will be presented binaurally at 65 ± 5 decibel(dB). The click train
      repetition frequencies will be 40 Hz and presented in the context of an auditory oddball
      paradigm to ensure participant attention to the stimuli. This task will be done while
      participants undergo EEG recordings.
    

Intervention name(s): Ketamine
Intervention type(s): Drug
Intervention description(s): Ketamine Hydrochloride Injection
Other intervention name(s): Ketamine Hydrochloride
Intervention MeSH terms: Ketamine
Intervention model: Single Group Assignment
Intervention model description: Open-label
Masking: None (Open Label)
Primary purpose: Treatment