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Neurostimulation Therapeutics in Psychiatry —The Promise and Potential Pitfalls

Neurostimulation Therapeutics in Psychiatry —The Promise and Potential Pitfalls

A 14th century approach to neurostimulation? © EVERETT HISTORICAL/SHUTTERSTOCK© Everett Historical/Shutterstock.com
TABLE. Characteristics of neurostimulation approachesTABLE. Characteristics of neurostimulation approaches

The potential for therapeutic applications of electromagnetic energy to the brain has long been recognized. The earliest recorded report of neurostimulation was that of Mesopotamian physician Scribonius Largus who applied a live torpedo fish on the scalp to treat headache. The modern era has seen an exciting emergence of research and clinical applications in neurostimulation-based therapeutics for psychiatric disorders. Such therapeutics offer a set of alternatives that are mechanistically distinct from and fundamentally different in mode of delivery and adverse-effect profile from pharmacologic interventions.

Neurostimulation is often referred to as “neuromodulation,” which the International Neuromodulation Society more broadly defines as “the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body.” Thus, electrical or magnetic neurostimulation is one method of altering nerve activity in a targeted fashion and represents a paradigm shift in the conceptualization and development of therapeutics for brain disorders. Accordingly, it confers some unique therapeutic advantages over medications but may also elicit different kinds of potential adverse effects that need to be thoughtfully studied and mitigated.

Neurostimulation approaches

“Targeted fashion” is perhaps the most critical aspect of neurostimulation that distinguishes it from medications, which generally have no substantive neuroanatomic specificity in their application. In contrast, neurostimulation approaches have much better spatial resolution. At a minimum, all brain stimulation methods have limited or no effects “below the neck.”

Some approaches such as standard applications of transcranial direct current stimulation (tDCS) have poor spatial selectivity (centimeters), but the most selective approach in the form of deep brain stimulation (DBS) can have a spatial resolution of approximately 1 mm. Most other neurostimulation approaches have spatial resolutions intermediate to these 2 extremes, with the exception of convulsive approaches (ECT and magnetic seizure therapy).

One of the great advantages of neurostimulation as a therapeutic is the focality of application, which spares other brain regions as well as other organ systems of the body from exposure to the treatment. In addition to differences in spatial resolution, neurostimulation approaches vary in other aspects including their depth of penetration, whether they are invasive or non-invasive, convulsive or non-convulsive, and whether energy is delivered in electric or magnetic form (Table).

While this mechanistically novel and spatially selective array of therapeutics offers a beacon of hope against a backdrop of a relatively poor track record in the development of novel pharmacologic interventions, we should be clear about the underlying assumptions regarding the mode of action. Such clarity will help us in demarcating the potential theoretical limits of therapeutic efficacy, in pointing to potential adverse effects, and in refining treatment parameters as advances in basic and clinical science prompt updating of these assumptions.

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