Procognitive Effects of Adjunctive D-Cycloserine to Intermittent Theta-Burst Stimulation in Major Depressive Disorder: Effets procognitifs de la D-cyclosérine en traitement complémentaire par la stimulation thêta-burst intermittente dans le trouble dépressif caractérisé.

Abstract

Objective: Major depressive disorder (MDD) is associated with cognitive impairments that persist despite successful treatment. Transcranial magnetic stimulation is a noninvasive treatment for MDD that is associated with small procognitive effects on working memory and executive function. We hypothesized that pairing stimulation with N-methyl-D-aspartate (NMDA) receptor agonism would enhance the effects of stimulation and its procognitive effects.

Method: The effect of NMDA receptor agonism (D-cycloserine, 100 mg) on cognitive performance was tested in two randomized double-blind placebo-controlled trials: (1) acute effects of in the absence of stimulation (n = 20 healthy participants) and (2) a treatment study of individuals with MDD (n = 50) randomized to daily intermittent theta-burst stimulation (iTBS) with placebo or D-cycloserine for 2 weeks. Cognitive function was measured using the THINC-it battery, comprised of the Perceived Deficits Questionnaire, the Choice Reaction Time, the Trail Making Test, the Digit Symbol Substitution Test, and the 1-Back tests.

Results: D-cycloserine had no acute effect on cognition compared to placebo. iTBS + D-cycloserine was associated with significant improvements in subjective cognitive function and correct responses on the 1-Back when compared to iTBS + placebo. Improvements in subjective cognition paralleled depressive symptoms improvement, however 1-Back improvements were not attributable to improvement in depression.

Conclusions: An intersectional strategy pairing iTBS with NMDA receptor agonism may restore cognitive function in MDD.