Accelerated Intermittent theta-burst stimulation with D-cycloserine Augmentation for DEPression – (AIDA-DEP)

The purpose of this study is to test the hypothesis of increased antidepressant efficacy of accelerated intermittent theta-burst stimulation (aiTBS) in depression through concomitant modulation of the N-methyl-D-aspartate receptor (NMDAR).

The specific aim is to evaluate the effect of augmentation with the partial NMDAR agonist D-cycloserine during aiTBS for depressive symptoms in a placebo controlled randomized controlled trial.

In this multicenter study we will recruit 90 patients, 18-years and older with an ongoing major depressive episode referred for clinical iTBS.

Study participants will be randomized to receive either 100 mg D-cycloserine or placebo at each treatment day with aiTBS (6 sessions/day) in a double-blinded fashion during nine week-days.

Primary outcome is change in depressive symptoms on the Montgomery–Åsberg Depression Rating Scale (MADRS) after the intervention.

Secondary outcomes are change in Clinical Global Impression, as well as in weekly patient reported outcomes of depressive symptoms, and side-effects, including a four-week and six-month follow-up. We will also explore if the effects of D-cycloserine is more pronounced in patients with impaired neuroplasticity.

If efficacy is demonstrated D-cycloserine augmented aiTBS could readily be implemented in clinical practice to decrease the disease burden of treatment resistant depression. Further, it may also serve as a long-awaited inpatient treatment alternative for rapid depressive symptom control.