None listed
Conditions
Brief summary
Major Depressive Disorder (MDD) is a common and debilitating condition with high rates of treatment resistance. Repetitive Transcranial Magnetic Stimulation (rTMS) is an established treatment for TRD with few adverse effects. Intermittent theta burst stimulation (iTBS) is a novel and time-efficient form of rTMS with evidence base in the treatment of treatment-resistant depression. The drug D-cycloserine (DCS) is a has demonstrable impact on rTMS and iTBS’s neuromodulatory effects. This study protocol proposes the conduct of a prospective multi-site, parallel-arm design, randomized, double-blinded, placebo-controlled clinical trial to investigate DCS augmentation of iTBS in MDD. We will investigate if adjuvant DCS 50mg or 100mg/day might have superior iTBS antidepressant effects. We hypothesise that iTBS administered 2-hours after ingestion of DCS 50mg or 100mg will be more effective in treating depressive symptoms compared with iTBS administered 2-hour after ingestion of placebo.
Interventions
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 cortex (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
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 cortex (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.
Sponsors
Alfred Health
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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.
Exclusion criteria
1. Inability to provide informed consent. 2. Medically unstable patients at the discretion of the investigator. 3. Concomitant neurological disorder or a history of a seizure disorder. 4. Participants who are pregnant. 5. Current substance use meeting DSM-5 criteria for substance use disorder. 6. Per DSM-5, had ever met diagnostic criteria for schizophrenia, schizoaffective disorder, schizophreniform disorder or delusional disorder as assessed by the MINI at the time of screening. 7. Diagnosis with antisocial, paranoid, schizoid or schizotypal personality disorder as per DSM-5 criteria and any other personality disorder at screening that significantly affects current psychiatric status and assessed as likely to impact trial participation, in the clinical judgement of investigator. 8. Diagnosis of any other mental disorder (in addition to those as described in Exclusion Criteria 5, 6 and 7) that is the participant’s primary diagnosis at the time of screening, in the clinical judgement of the investigator.
Outcome results
None listed