D-cycloserine for Major Depressive Disorder
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional
Phase: Phase 2

Summary: 
      For many depression patients treatment changes are required, including switching to another
      antidepressant and addition of a second antidepressant or a non-antidepressant agent
      ("augmentation"). The need to modify treatment is usually necessary because of partial or no
      response to first-line monotherapy or the failure to achieve remission although treatment
      response (improvement) has been obtained. These caveats of presently available antidepressant
      drugs highlight the need for innovative pharmacological treatment strategies. Recent data
      suggest that N-methyl-D-aspartate receptor (NMDAR) antagonists and partial agonists at the
      NMDAR-associated glycine binding site may represent a novel type of antidepressant
      medications. These types of compounds protect vulnerable neurons against a variety of
      insults, including stress-induced damage, and may serve to enhance and maintain normal
      synaptic connectivity. In animal models, these compounds mimic the effects of clinically
      effective antidepressants. Furthermore, down-regulation of the glycine site of the NMDAR was
      found to be a common feature of currently used antidepressant medications. D-cycloserine (DCS
      , Seromycin) is a broad spectrum antibiotic, in use for over thirty years against
      tuberculosis, that acts as a partial agonist at the NMDAR-associated glycine site. Beneficial
      antidepressant effects have been reported with 500-1000 mg/day DCS regimens in depressed
      tuberculosis patients and recent preliminary findings suggest that DCS may also be beneficial
      in the treatment of major depressive disorder. The antidepressant effects of DCS seem to
      reflect consequences of its capacity to reduce NMDAR receptor function. In the present
      project, it is proposed to assess, using a random assignment, parallel-group, double blind,
      placebo controlled design, the effects of a NMDAR -antagonist DCS dose regimen, 250 --> 1000
      mg/day for 6 wks, as adjuvant pharmacotherapy for treatment-resistant major depressive
      disorder patients. The study methodology includes the assessment of DCS effects upon symptoms
      profile, neurocognitive tests performance, amino acids serum levels, and brain
      electrophysiology parameters associated with the prepulse inhibition-startle response
      paradigm. It is hypothesized that significant beneficial DCS treatment effects will be
      registered.
    


Intervention name(s): D-cycloserine
Intervention type(s): Drug
Intervention description(s): D-cycloserine (DCS , Seromycin) is a broad spectrum antibiotic, in use for over thirty years against tuberculosis, that acts as a partial agonist at the NMDAR-associated GLY site.
Intervention MeSH terms: Cycloserine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Major depressive disorder; NMDA receptor; Treatment-Resistant; D-cycloserine