Please select the outcome measures that correspond to the clinical trial below.
Title: N-methyl-D-aspartate Receptor (NMDAR)-Based Pharmacotherapy With D-cycloserine for Treatment-resistant Major Depressive Disorder
Brief 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.


Options:
A: Number of Patients Demonstrating a > 50% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) (Received drug for 8 weeks during week 0 to week 8 of the study); Number of Patients Demonstrating a > 50% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) (Received drug for 8 weeks during week 9 to week 16 of the study); Number of Patients Demonstrating a > 30% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) (Received drug for 8 weeks during week 0 to week 8 of the study); Number of Patients Demonstrating a > 30% Decrease in Depression Scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) (Received drug for 8 weeks during week 9 to week 16 of the study)
B: Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at 24 Hours Post First Dose (Last Observation Carried Forward [LOCF] Data): Double-blind (DB) Treatment Phase (Baseline (Day 1, predose) and 24 hours first post dose (Day 2)); Change From Baseline in Clinical Global Impression-Severity of Suicidality - Revised (CGI-SS-R) Scale at 24 Hours Post First Dose (LOCF Data): DB Treatment Phase (Baseline (Day 1, predose) and 24 hours first post dose (Day 2))
C: The primary objective is to determine whether an antidepressant effect can be achieved in patients with Treatment Resistant Depression determined by a change from baseline in the MADRS total score. (Change from Baseline)
D: Change in 24 item Hamilton Depression Rating Scale (HAMD) scores. Safety measures: UKU scale, vital signs assessments, laboratory parameters (SMA-20, CBC, UA) (6 weeks); Change in Hamilton Rating Scale for Anxiety (HAMA) scores. (6 weeks)

Answer: D