ONE-P TMS First Responders

One-day rTMS + D-cycloserine to Treat PTSD in First Responders

The aim of this study is to examine the feasibility and tolerability of a one-day protocol of repetitive transcranial magnetic stimulation with D-cycloserine (DCS) as an augmentation strategy in first responders who have PTSD.

In this feasibility and tolerability trail, 50 patients with PTSD will be recruited at UBC. Patients will be randomised to receive either aiTBS plus DCS or aiTBS plus placebo DCS. The primary outcome is to evaluate the feasibility and tolerability of active aiTBS plus D-Cycloserine (DCS) versus active aiTBS plus placebo-DCS, using a one-day regimen of 15 treatment sessions, in active military personnel or veterans who suffer PTSD. A secondary aim is to explore preliminary signal of clinical efficacy of active aiTBS plus D-Cycloserine (DCS) on the primary outcome to inform sample size calculation for a definitive trial.

Inclusion Criteria:

• are outpatients between the ages of 19-60;
• are voluntary and competent to consent;
• are first responders (active, on leave or retired);
• have DSM-5 diagnosis of PTSD with a CAPS for DSM-5 (CAPS-5) score ≥ 25;
• 17-item Hamilton Depression Rating Scale score ≤ 23;
• have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening;
• if participating in psychotherapy, must have been in stable treatment for at least 1 month prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study;
• able to adhere to the treatment schedule;
• Pass the TMS adult safety screening (TASS) questionnaire, and the MRI safety screening.

Exclusion Criteria:

• have a Severe Substance Use Disorder (except tobacco) within the last three (3) months;
• have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump;
• have active suicidal intent;
• are pregnant;
• have a lifetime MINI diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms;
• have a MINI diagnosis of OCD, or mood disorder that is assessed by a study investigator to be primary and causing greater impairment than PTSD;
• have a diagnosis of any personality disorder, assessed by a study investigator to be primary and causing greater impairment than MDD;
• have failed a course of ECT in the current episode or previous episode;
• have received rTMS for any previous indication;
• have any significant neurological disorder, history of seizure disorder (except those therapeutically induced by ECT), or any significant head trauma with clear radiological evidence of cerebrovascular injury on imaging;
• have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed;
• clinically significant laboratory abnormality, in the opinion of the one of the principal investigators or study physicians (including but not limited to abnormal blood urea nitrogen (BUN), creatinine, estimated glomerular filtration rate (eGFR));
• currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy;
• currently take dicumarol, gingko biloba, isoniazid, ethionamide, fluphenazine, metrizamide, tramadol, warfarin due to potential interactions with D-Cycloserine;
• planned vaccination with Bacille Calmette-Guérin, cholera or typhoid or planned imaging procedure with an injectable die, within one week following the treatment days, due to potential interactions with DCS.
• allergy to DCS