{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:26:15Z","timestamp":1792553175884,"version":"4.5.0"},"reference-count":40,"publisher":"American Medical Association (AMA)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"Importance<\/jats:title>The antidepressant effects of transcranial magnetic stimulation protocols for major depressive disorder (MDD) are thought to depend on synaptic plasticity. The theta-burst stimulation (TBS) protocol synaptic plasticity is known to be N<\/jats:sc><\/jats:italic>-methyl-D<\/jats:sc>-aspartate (NMDA)\u2013receptor dependent, yet it is unknown whether enhancing NMDA-receptor signaling improves treatment outcomes in MDD.<\/jats:p><\/jats:sec>Objective<\/jats:title>To test whether low doses of the NMDA-receptor partial-agonist, D<\/jats:sc>-cycloserine, would enhance intermittent TBS (iTBS) treatment outcomes in MDD.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This was a single-site 4-week, double-blind, placebo-controlled, randomized clinical trial conducted from November 6, 2019, to December 24, 2020, including 50 participants with MDD. Participants were recruited via advertisements and referral. Inclusion criteria were as follows: age 18 to 65 years with a primary diagnosis of MDD, a major depressive episode with score of 18 or more on the 17-item Hamilton Depression Rating Scale, a Young Mania Rating Scale score of 8 or less, and normal blood work (including complete blood cell count, electrolytes, liver function tests, and creatinine level).<\/jats:p><\/jats:sec>Interventions<\/jats:title>Participants were randomly assigned 1:1 to either iTBS plus placebo or iTBS plus D<\/jats:sc>-cycloserine (100 mg) for the first 2 weeks followed by iTBS without an adjunct for weeks 3 and 4.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was change in depressive symptoms as measured by the Montgomery-\u00c5sberg Depression Rating Scale (MADRS) at the conclusion of treatment. Secondary outcomes included clinical response, clinical remission, and Clinical Global Impression (CGI) scores.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 50 participants (mean [SD] age, 40.8 [13.4] years; 31 female [62%]) were randomly assigned to treatment groups: iTBS plus placebo (mean [SD] baseline score, 30.3 [4.2]) and iTBS plus D<\/jats:sc>-cycloserine (mean [SD] baseline score, 30.4 [4.5]). The iTBS plus D<\/jats:sc>-cycloserine group had greater improvements in MADRS scores compared with the iTBS plus placebo group (mean difference, \u22126.15; 95% CI, \u22122.43 to \u22129.88; Hedges g<\/jats:italic>\u2009=\u20090.99; 95% CI, 0.34-1.62). Rates of clinical response were higher in the iTBS plus D<\/jats:sc>-cycloserine group than in the iTBS plus placebo group (73.9% vs 29.3%), as were rates of clinical remission (39.1% vs 4.2%). This was reflected in lower CGI-severity ratings and greater CGI-improvement ratings. No serious adverse events occurred.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>Findings from this clinical trial indicate that adjunctive D<\/jats:sc>-cycloserine may be a promising strategy for enhancing transcranial magnetic stimulation treatment outcomes in MDD using iTBS requiring further investigation.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT03937596<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2022.3255","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T15:13:09Z","timestamp":1665587589000},"page":"1153","source":"Crossref","is-referenced-by-count":102,"title":["Efficacy of Adjunctive D<\/scp>-Cycloserine to Intermittent Theta-Burst Stimulation for Major Depressive Disorder"],"prefix":"10.1001","volume":"79","author":[{"given":"Jaeden","family":"Cole","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Calgary, Calgary, 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