Neurotherapeutic Interventions for Psychiatric Illness

Abstract

Many patients with mental illness do not respond to common evidence-based treatments such as psychopharmacology and psychotherapy. We increasingly understand these illnesses as disorders of brain circuits, suggesting that otherwise treatment-refractory patients might be helped by direct intervention in those circuits. Non-invasive techniques for circuit intervention include electro-convulsive therapy (ECT) and transcranial magnetic stimulation (TMS). Circuits can also be targeted more directly and focally through neurosurgical intervention, including through vagus nerve stimulation (VNS), ablative neurosurgery (cingulotomy and capsulotomy), cortical brain stimulation (EpCS), or deep brain stimulation (DBS). Each of these approaches has evidence supporting its use in a major psychiatric disorder, although many have yet to demonstrate a strong clinical signal in a randomized controlled trial. New technologies that may aid in that demonstration include non-invasive techniques that can focus energy more precisely in the deep brain and invasive devices that respond in real time to changes in brain activity (closed-loop stimulation). In this article, we review the modalities and evidence base for these neurotherapeutics, with an emphasis on their clinical readiness and relative advantages.

Anti-Suicidal Efficacy of Repetitive Transcranial Magnetic Stimulation in Depressive Patients: A Retrospective Analysis of a Large Sample

“…In comparison to ECT, although the latter seem to have higher response rates in treatment-resistant depression (41), rTMS does not require anesthesia or muscle relaxation (does not require induction of a seizure). Moreover, the magnetic stimulation is delivered in a focal manner at a chosen cortical target rather than affecting the entire brain as with ECT (42), which significantly reduces side effects (43). Furthermore, there is no evidence of cognitive impairment connected to TMS, also most adverse events of TMS are mild to moderate in intensity, which leads to a low discontinuation rate due to adverse events during the treatment course (40).…”

Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression

“…Mood and anxiety symptoms are also linked to deep brain structures (Williams, 2016 ), raising the possibility that DBS may be more effective than non-invasive stimulation that affects only the cortical mantle. The history of successful stereotactic lesioning for severe depression and obsessive-compulsive disorder (OCD) patients further supports that theory (Park et al, 2006 ; Dougherty and Widge, 2017 ). DBS has thus been tested in multiple brain areas for severe depressive symptoms, with strong open-label responses and a mixed picture in randomized controlled trials.…”

Closing the Loop on Deep Brain Stimulation for Treatment-Resistant Depression

“…Mood and anxiety symptoms are also linked to deep brain structures (Williams, 2016), raising the possibility that DBS may be more effective than non-invasive stimulation that affects only the cortical mantle. The history of successful stereotactic lesioning for severe depression and obsessive-compulsive disorder (OCD) patients further supports that theory (Park et al, 2006;Dougherty and Widge, 2017). DBS has thus been tested in multiple brain areas for severe depressive symptoms, with strong open-label responses and a mixed picture in randomized controlled trials.…”