Neuromodulation in Psychiatry: State-of-the-Art & Future Directions

Despite the best of the available psychopharmacological treatments & psychosocial interventions, about 20 – 30% of patients with psychiatric disorders show partial or no clinical improvement and persist in having symptoms that contribute to disability. Contextually, neuromodulatory techniques are increasingly being used to treat symptoms that are resistant to psychotropic treatments. These include non-invasive brain stimulation techniques (NIBS) [ such as Electroconvulsive therapy (ECT), Transcranial Magnetic Stimulation (TMS), and transcranial Direct Current Stimulation] and invasive techniques (like Deep Brain Stimulation).

Evidence for therapeutic efficacy and clinical applicability from NIBS studies has been mixed with inter-individual heterogeneity in response (Lefaucheur et al., 2014, Kuo et al., 2017). Research on the differential response of these treatment-resistant patients to one of these NIBS techniques requires face-to-face studies comparing respective neuromodulatory interventions with cross-over design; however, such studies are rare. Such studies are, however, relevant to explore the mechanistic foundation of these interventions and, on these grounds, to optimize respective approaches. Furthermore, such studies have the potential to reveal vital clues about the biology of complex psychiatric disorders (Polania et al., 2018).

There are ongoing efforts to implement such studies that address these nuanced aspects of brain stimulation in treating psychiatric disorders (Venkatasubramanian et al., 2020). Meanwhile, it is equally important to summarize and critically evaluate the existing evidence to understand the evidence status of brain stimulation in the treatment of psychiatric disorders.

Given the paucity of head-to-head comparison studies assessing the efficacy of different repetitive transcranial magnetic stimulation (rTMS) protocols in OCD, network meta-analysis facilitates simultaneous comparison of multiple treatments using statistical techniques involving a single analysis through conjoint evaluation of direct and indirect evidence within a network of available randomized controlled trials (Rouse et al., 2017). One such report appears in this issue, in which the authors have critically examined the comparative efficacy of different rTMS in the treatment of obsessive-compulsive disorders (Vinod et al. [in this issue]); this network meta-analysis suggested rTMS protocols that target dorsolateral prefrontal cortex and medial prefrontal cortex / anterior cingulate cortex are promising and higher ranked.

Yet another avenue to leverage the potential of brain stimulation techniques is to combine them with other interventions that have shown complementary therapeutic effects. One such novel application is combining deep brain stimulation with capsulotomy to treat Tourette’s syndrome; this combination approach is motivated by background evidence that deep brain stimulation benefits motor symptoms, whereas capsulotomy helps psychiatric symptoms. The study by Wang et al. (in this issue) reports that combined deep brain stimulation with capsulotomy has acceptable safety and is effective in amelioration of motor and psychiatric symptoms in the treatment of Tourette’s syndrome.

In this context, it is noteworthy that different forms of NIBS affect neural activity and neuroplasticity in distinct ways, which has important implications for their clinical efficacy (Sale et al., 2015). Aberrant neuroplasticity is a critical component of pathogenesis in several psychiatric disorders, including schizophrenia and depression (Mehta et al., 2019). Hence, concurrent assessment of neuroplasticity measures (for example, TMS experiments, neuroplasticity gene polymorphism) along with multi-level neurobiological parameters and clinical symptom scores will enable disease modeling; furthermore, combining these measures with carefully controlled NIBS experiments might unravel mechanistic basis & prognostic biomarkers of these neuromodulatory techniques (Venkatasubramanian et al., 2020).