Adjunctive D-cycloserine may enhance antidepressant effect of transcranial magnetic stimulation in MDD

Participants were randomly assigned 1:1 to either iTBS plus placebo or iTBS plus D-cycloserine (100 mg) for the first 2 weeks followed by iTBS without an adjunct for weeks 3 and 4.

The primary outcome was change in depressive symptoms as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at the conclusion of treatment. Secondary outcomes included clinical response, clinical remission, and Clinical Global Impression (CGI) scores.

The study found that:

1. The iTBS plus D-cycloserine group had greater improvements in MADRS scores compared with the iTBS plus placebo group.

2. Rates of clinical response were higher in the iTBS plus D-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.

3. No serious adverse events occurred.

These findings are important, because if replicated in large multicenter studies, an adjunct is deployable within existing TMS and health systems infrastructure to improve outcomes in MDD.

Results of this randomized clinical trial suggest that adjunctive DCS may be a promising strategy for improving TMS treatment outcomes in MDD using iTBS. Replication in a larger multisite study is required, as is additional investigation into intersectional approaches with other dosing regimens and precision medicine targeting approaches.

Source: JAMA Psychiatry: doi:10.1001/jamapsychiatry.2022.3255