D-Cycloserine Augmentation of Intermittent Theta Burst Stimulation (iTBS) in Depression

INTERVENTION: All eligible participants will receive iTBS therapy, which will be administered at the Monash Alfred Psychiatry Research Centre (MAPrc) by trained research staff. TMS will be administered with a Neurosoft‐MS/D magnetic stimulator. Stimulation is applied to the left dorsolateral prefrontal corte X(DLPFC) and stimulation intensity will be at 90% of the individual’s calibrated resting motor threshold. Each iTBS treatment session delivers 600 pulses and is approximately 3½ minutes in duration. iTBS treament sessions will be administered daily, 5 days a week for 4 weeks. Participants in the treatment arm will be required to ingest an oral capsule of either 50mg of D‐Cycloserine (DCS) or 100mg DCS 2‐hours prior to each iTBS treatment session (i.e. 5 days a week for 4 weeks). The recording of self‐reported ingestion times of DCS will be used to monitor adherence with the study protocol. CONDITION: Major Depressive Disorder; ; Major Depressive Disorder Mental Health ‐ Depression PRIMARY OUTCOME: Montgomery Åsberg Depression Rating Scale (MADRS)[Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment] SECONDARY OUTCOME: Beck’s Anxiety Inventory (BAI)[Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment] Beck’s Scale for Suicide Ideation (BSS)[Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment] Clinical Global Impression (CGI)[Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment] Quick Inventory of Depressive Symptomatology – Self Report (QIDS‐SR)[Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment] The International Trauma Questionnaire (ITQ)[Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment] World Health Organization Quality of Life (WHOQOL‐BREF)[Baseline and at the ends of weeks 1, 2, 3 and 4 of treatment] INCLUSION CRITERIA: 1. Diagnosis of major depressive episode (MDE), in accordance with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM‐5), in the context of unipolar major depressive disorder or bipolar affective disorder. 2. 18 years or older in age. 3. Treatment resistant depression at Stage II of the Thase and Rush classification. 4. Baseline Montgomery Åsberg Depression Rating Scale score of greater than or equal to 20 (moderate‐to‐severe depression severity). 5. No increase or initiation of new antidepressant therapy in the four weeks prior to screening. 6. Demonstrated capacity to give informed consent.