rTMS for Peripartum Depression

Repetitive Transcranial Magnetic Stimulation (rTMS) is a neuromodulatory technique that is effective in major depression. There is preliminary evidence suggesting that rTMS is effective in peripartum depression as well, however this comes from a number of very small studies.

The objective is to study the effectiveness of rTMS in peripartum depression. The investigators will do so using an open label design in which participants will receive rTMS for four weeks. The focus is on clinical improvement in depressive symptoms; however the investigators will also look at other aspects such as perinatal anxiety and maternal-infant bonding as measured by self-report questionnaires.

Peripartum Depression (PPD) is common and severely disabling. Pharmacological intervention remains the first line of treatment, however many patients do not experience any benefits from them. Furthermore, many women are hesitant about pharmaceutical interventions due to the unknown effects on foetal health and lactation. Hence novel treatment approaches are required for such patients. Neuromodulation techniques involve selective targeting of brain areas which are promising avenues for such depressed patients.

Transcranial magnetic stimulation (rTMS) is an investigational and therapeutic modality that impacts neurons by delivering patterned energy safely and noninvasively. In response to this patterned energy, neurons fire, and adapt by changing their connection strengths. This change in connection strength is believed to be the underlying mechanism whereby rTMS has therapeutic benefit in conditions such as Major Depressive Disorder (MDD). There are preliminary evidences suggesting that it is effective in PPD as well, however this comes from a number of very small studies and is therefore unclear.

Given the promising preliminary evidence, the investigators propose to study the effectiveness of intermittent Theta-Burst Stimulation rTMS (iTBS) to the left dorsolateral prefrontal cortex (DLPFC) in treating PPD. Participants with PPD will receive iTBS rTMS for four weeks (20 sessions) in an open label manner. The primary measure will be clinical improvement in depressive symptoms as measured by change in the Montgomery-Asberg Depression Rating Scale (MADRS) with iTBS-rTMS. In addition, the investigators will look at other aspects such as peripartum anxiety and maternal attachment during treatment and 8 weeks postpartum.

Eligibility Criteria:
Inclusion Criteria:

* Women currently experiencing peripartum depression as determined by the MINI-International Neuropsychiatric Interview
* Depressive episode of at least moderate severity, as indicated by a score of ≥15 (ante-partum) or ≥12 (post-partum) on the Edinburgh Post-Natal Depression Scale (EPNDS).
* Are currently pregnant or 1 month post-delivery
* Refuse antidepressant therapy, or have depression that has not improved with psychotropics and/or psychotherapy
* Be willing to remain on a stable medication regimen for 2 weeks prior the study and during the study
* Aged 18-40 years

Exclusion Criteria:

* Epilepsy, history of seizures or pre-eclampsia
* Previous Stroke
* Current Alcohol Use Disorder
* History of psychosis
* Bipolar Disorder
* Current suicidal ideation
* Intracranial metallic objects (dental hardware is not an exclusionary criteria)
* Unstable medical condition
* have failed a course of 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 any significant obstetrical complications
* 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
* have a clinically significant laboratory abnormality, in the opinion of study physician
* are currently (or in the last 4 weeks) taking lorazepam greater than 2 mg daily (or equivalent) due to the potential to limit rTMS efficacy
* are currently (or in the last 4 weeks) taking lorazepam greater than or equal to 2 mg daily