D-Cycloserine+iTBS PK Study

Methods: An open-label study of D-cycloserine (DCS) pharmacokinetics will be performed in patients undergoing iTBS to the left DLPFC as a treatment for Major Depressive Disorder. Twelve patients (males and females aged 18-65, with a score ≥18 on the Hamilton Rating Scale for Depression-17 items, and stable pharmacological and psychological regimens) with an acute Major Depressive Episode will be recruited. Bloodwork and an echocardiogram will be obtained prior to the initiation of the study, and enrollment in the study will be contingent on normal lab results. Prior to initiating iTBS treatment, participants will receive one oral dose of 100mg DCS. A pharmacokinetic curve will be generated from D-Cycloserine levels obtained at 6 timepoints; pre-ingestion, +30 mins, + 60 mins, + 90mins, +120mins and +24 hrs. Participants will receive iTBS daily for 4 weeks (20 sessions). All participants will be provided with weight-based dosing of DCS to take 120 minutes prior to each iTBS session. Serum levels of weight-based DCS dosing will be measured by blood draws at several time points throughout iTBS treatment. Specifically, a pharmacokinetic curve will be generated on Day 1 of iTBS treatment from D-Cycloserine levels obtained at 6 timepoints; pre-ingestion, +30 mins, + 60 mins, + 90mins, +120mins and +24 hrs. Additional time points will be obtained prior to and 120 minutes after the fifth dose (Day 5 of TMS) and prior to and 120 minutes after the sixth dose (Day 6 of TMS, corresponding to the beginning of the second week of TMS). Antidepressant effects will be quantified using the Montgomery Asberg Depression Rating Scale, a gold standard clinician rated instrument. Participants will complete a short battery of cognitive tests at the beginning and end of the study. Blood work and echocardiogram will be repeated after 4 weeks to confirm safety of low-dose DCS. Participants will return to the lab for a follow-up assessment 4 weeks after they have finished the TMS protocol (week 8).