Objectives: Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that causes changes in cortical excitability. Recent double-blind placebo-controlled clinical trials suggest that tDCS may be efficacious in the treatment of depression. Pharmacological agents that prolong the effects of tDCS could lead to greater cumulative changes in cortical excitability, producing greater and more prolonged efficacy. One agent shown to prolong the excitability-enhancing effects of tDCS in healthy subjects is D-Cycloserine, a partial agonist at the glycine-binding site of N-methyl-D-aspartate receptors. We investigated whether combining prefrontal tDCS with D-Cycloserine could enhance and/or prolong the antidepressant effect of tDCS.
Methods: Five depressed subjects who had relapsed or failed to achieve remission after receiving a previous course of prefrontal tDCS were recruited. In this open-label pilot study, subjects ingested 100-mg D-Cycloserine 2 hours before tDCS sessions. Subjects received 20 minutes of tDCS at 2 mA on consecutive weekdays for a total of 20 sessions. The anode was placed at pF3 and the cathode at F8 (10/20 system). Clinical response was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS).
Results: The change in Montgomery-Åsberg Depression Rating Scale scores was not greater with the combination of D-Cycloserine and tDCS than had previously been produced by tDCS alone. No significant additional adverse effects were reported.
Conclusions: This pilot open-label study found that pretreatment with 100-mg D-Cycloserine 2 hours before tDCS was well tolerated but did not enhance the antidepressant efficacy of anodal prefrontal tDCS.
From the *School of Psychiatry, University of New South Wales, Sydney, Australia; †Black Dog Institute, Sydney, Australia; ‡Department of Psychiatry, Singapore General Hospital, Singapore; §Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia and ∥St George Hospital, South Eastern Sydney Health, Sydney, Australia.
Received for publication October 15, 2012; accepted November 27, 2012.
Reprints: Colleen K. Loo, MD, FRANZCP, Black Dog Institute, Hospital Road, Randwick, 2031, Australia (e-mail: firstname.lastname@example.org).
Conflicts of Interest and Source of Funding: Dr Loo received honoraria from Eli Lilly, Pfizer/Wyeth, Astra Zeneca, Servier; the remaining authors declared no conflicts of interest.
Australian National Health and Medical Research Council Grant #510142 funded this work.