Adjunctive D-Cycloserine in Major Depressive Disorder

• Status: Active, not recruiting
• Trial end date: 2021-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Transcranial magnetic stimulation (rTMS) is an approved treatment for depression. The purpose of this study is to test an adjunctive medication, D-cycloserine, in rTMS for depression using a placebo-controlled design. D-Cycloserine is a partial N-Methyl-D-Aspartate receptor (NMDAr) agonist, and therefore may enhance the effects of rTMS, however there is data to support and refute this hypothesis. Using a double-blind design, the investigators will randomize patients with Major Depressive Disorder to receive either daily low dose D-cycloserine or placebo in conjunction with rTMS to the left dorsolateral prefrontal cortex. After 10 treatments (2 weeks), this double-blind period will conclude and all participants will receive an additional 10 treatments (2 weeks) of rTMS without any adjuncts. The primary outcome will be improvement in clinician rated depressive symptoms at the conclusion of the study.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Calgary
• Treatments: Cycloserine

Criteria

Inclusion Criteria:

• are competent to consent to treatment

• have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of DSM-5 criteria Major Depressive Disorder with a current episode of at least moderate severity of depression, single or recurrent

• have failed to achieve a clinical response to one adequate trial of antidepressant medication within the current episode, or been unable to tolerate antidepressant medications.

• have a score ≥ 18 on the Hamilton Depression Rating Scale 17-item

• have a Young Mania Rating Scale Score of ≤ 8

• have had no change in dose, or initiation of any psychotropic medication in the 4 weeks prior to randomization

• are able to adhere to the treatment schedule

• pass the TMS adult safety screening (TASS) questionnaire

Exclusion Criteria:

• Allergy to Cycloserine

• Have failed adequate trials of ≥4 antidepressant treatments in the current episode.

• have an alcohol or substance use disorder within the last 3 months

• have suicidal ideation (score of 4 ≥ on item 10 of MADRS)

• are at a significant risk of harm to themselves or others

• history of psychosis

• are currently pregnant , breast feeding or plan to become pregnant

• have a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of other primary psychiatric diagnoses as assessed by a study investigator to be primary and causing greater impairment than Major Depressive Disorder.

• have failed a course of electroconvulsive therapy (ECT) in the current episode. Previous ECT treatment outside of the current episode does not influence inclusion.

• history of non-response to rTMS treatment.

• have any significant neurological disorder or insult including, but not limited to:

any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of epilepsy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than or equal to 5 minutes

• have concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump

• 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

• If participating in psychotherapy, must have been in stable treatment for at least 3 months 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

• are currently (or in the last 4 weeks) taking lorazepam or any other benzodiazepine due to the potential to limit rTMS efficacy

• have an exclusion criteria for MRI: Those with a history of cranial, thoracic or abdominal surgery, with pacemakers, artificial joints or other metallic implants will be excluded from the MRI scan. Subjects that have agreed to participate in the MRI portion of the study will be pre-screened for any potential metal fragments in the body (particularly in the orbits) if they have had any history of doing metal work or have been involved in use/deployment of ammunitions/explosives, welding, piping etc).