The following is a summary of “Efficacy of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation for Major Depressive Disorder” published in the October 2022 issue of Psychiatry by Cole et al.


Synaptic plasticity was hypothesized to have a role in how transcranial magnetic stimulation for major depressive disorder (MDD) works as an antidepressant. N-methyl-D-aspartate (NMDA)-receptor dependence is known for the theta-burst stimulation (TBS) protocol synaptic plasticity, however, it was unclear if boosting NMDA-receptor signaling enhanced MDD treatment results. For a study, researchers sought to determine if intermittent TBS (iTBS) treatment results for MDD would be improved by modest dosages of the NMDA-receptor partial-agonist, D-cycloserine.

From November 6, 2019, to December 24, 2020, 50 people with MDD participated in a single-site, 4-week, double-blind, placebo-controlled, randomized clinical study. Ads and word-of-mouth recommendations were used to find participants. Age range from 18 to 65 years with a main diagnosis of MDD, a severe depressive episode with a score of 18 or higher on the 17-item Hamilton Depression Rating Scale, a Young Mania Rating Scale score of 8 or less, and normal blood work were the inclusion criteria (including complete blood cell count, electrolytes, liver function tests, and creatinine level). For the first two weeks, participants were randomly randomized 1:1 to receive either iTBS plus placebo or iTBS with D-cycloserine (100 mg), and then for weeks 3 and 4, iTBS was administered without an adjunct. The Montgomery-Åsberg Depression Rating Scale (MADRS) score change in depression symptoms at the end of therapy was the main result. Clinical remission, clinical response, and Clinical Global Impression (CGI) scores were considered secondary outcomes.

The therapy groups, iTBS plus placebo (mean [SD] baseline score, 30.3 [4.2]) and iTBS plus D-cycloserine (mean [SD] baseline score, 30.4 [4.5]), were randomly allocated to the 50 participants (mean [SD] age, 40.8 [13.4] years; 31 female [62%]). The iTBS plus D-cycloserine group improved MADRS scores more than the iTBS plus placebo group (mean difference, −6.15; 95% CI, −2.43 to −9.88; Hedges g = 0.99; 95% CI, 0.34-1.62). In comparison to the iTBS plus placebo group, the rates of clinical response and remission (39.1% vs. 4.2%) were greater in the iTBS plus D-cycloserine group (73.9% vs. 29.3%, respectively). Less severe CGI scores and higher CGI progress scores were indicators of it. No serious adverse event occurred.

The results of the clinical research pointed to adjunctive D-cycloserine as a method that merits additional study for improving the effectiveness of transcranial magnetic stimulation therapy for MDD utilizing iTBS.

Reference: jamanetwork.com/journals/jamapsychiatry/article-abstract/2796973