Accelerated TMS for Perinatal Depression

Perinatal depression is underdiagnosed, undertreated, and understudied. Approximately one in five individuals will experience perinatal depression, which spans from conception to one year after birth. Untreated perinatal depression increases the risk of stillbirth, preterm birth, substance abuse, parental suicide, and developmental delay. There are limited empirical data to guide treatment of perinatal depression. Psychotherapy can be effective for mild-to-moderate depression, but it is slow acting and difficult to access. Antidepressants show inconsistent benefits and safety; moreover, patients report feeling anxious or guilty about taking them. Transcranial magnetic stimulation (TMS) is FDA cleared treatment for major depressive disorder, adolescent depression, late life depression, and anxious depression. It has also shown promise as a safe and effective biological intervention for perinatal depression for both the mother and fetus. One of the most exciting new developments in neurostimulation is accelerated intermittent theta burst stimulation (iTBS), a TMS protocol that involves multiple daily treatments rather than once daily treatment. A specific accelerated TMS protocol called Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) was FDA cleared in September 2022 because of its rapid and robust antidepressant effects. In an open-label study (n=21), SNT significantly reduced depression in one day and yielded 90.5% remission after five days. Importantly, there is no evidence that accelerated TMS protocols pose more risk than conventional TMS protocols that have a strong safety profile. While SNT is a potential breakthrough treatment, it has not been tested in peripartum individuals. Accelerated iTBS may expedite depressive symptom improvement and reduce the need for pharmacotherapy for individuals struggling with perinatal depression. If tolerable and efficacious, this treatment modality may increase the viable treatment options available to peripartum women with depressive symptoms. In this pilot trial, patients who are currently pregnant or postpartum with treatment-resistant depression (n=12) will receive a modified SNT with neuronavigation. Treatment site location will be guided by MRI when possible given the promising internal findings highlighted above. However, if neuroimaging is not chosen by the patient, unsafe for the patient for any reason, or not tolerable for the patient, we will offer treatment with scalp-based measurement (i.e., TMS targeting based on Beam F3 method). Overall, this study is critically important for informing the viability of future accelerated iTBS trials in a peripartum population and may shape the future of affective treatment options in this patient group.