D-cycloserine enhances TMS treatment for depression

NMDA-receptor partial agonist D-cycloserine enhanced transcranial magnetic stimulation treatment outcomes in those with major depressive disorder, researchers reported.

The antidepressant effects of transcranial magnetic simulation for major depressive disorder (MDD) are thought to depend on synaptic plasticity, Jaeden Cole, BSc, of the department of psychiatry at the University of Calgary in Alberta, Canada, and colleagues wrote in JAMA Psychiatry.

According to Cole and colleagues, the theta-burst stimulation protocol synaptic plasticity is known as the NMDA-receptor dependent. However, it is unknown whether enhancing NMDA-receptor signaling improves treatment outcomes for MDD. Cole and researchers aimed to test whether low-doses of D-cycloserine would enhance treatment outcomes.

The researchers conducted a 4-week, double-blind, placebo-controlled, randomized trial. The 50 participants with MDD who were aged 18 to 65 years and had a primary diagnosis of MDD, with a major depressive episode with a score of 18 or higher on the Hamilton Depression Scale, as well as a Young Mania Rating Scale score of eight or lower.

Participants were randomly assigned at a 1:1 ratio to receive either intermittent theta-burst stimulation with 100 mg of D-cycloserine, or intermittent theta-burst stimulation with placebo.

Of the 50 participants (mean age, 40.8 years; 62% female), those who received placebo had a mean baseline score of 30.3 on the Montgomery-Asberg Depression Ratings Scale (MADRS), and those who received D-cycloserine had a mean baseline score of 30.4.

After treatment, those who received D-cycloserine had greater improvements in MADRS scores, compared with those who received placebo (mean difference, –6.15; 95% CI, –2.43 to –9.88). In addition, rates of clinical response were higher in those who received D-cycloserine compared with those who received placebo (73.9% vs. 29.3%), as well as rates of clinical remission (39.1% vs. 4.2%).

Cole and colleagues reported that no serious adverse events occurred.

“Results of this randomized clinical trial suggest that adjunctive [D-cycloserine] may be a promising strategy for improving TMS treatment outcomes in MDD using [intermittent theta-burst stimulation],” they wrote. “Replication in a larger multisite study is required, as is additional investigation into intersectional approaches with other dosing regimens and precision medicine targeting approaches.”