A Critical Review and Synthesis of Clinical and Neurocognitive Effects of Noninvasive Neuromodulation Antidepressant Therapies

There is a plethora of current and emerging antidepressant therapies in the psychiatric armamentarium for the treatment of major depressive disorder. Noninvasive neuromodulation therapies are one such therapeutic category; they typically involve the transcranial application of electrical or magnetic stimulation to modulate cortical and subcortical brain activity. Although electroconvulsive therapy (ECT) has been used since the 1930s, with the prevalence of major depressive disorder and treatment-resistant depression (TRD), the past three decades have seen a proliferation of noninvasive neuromodulation antidepressant therapeutic development. The purpose of this critical review was to synthesize information regarding the clinical effects, neurocognitive effects, and possible mechanisms of action of noninvasive neuromodulation therapies, including ECT, transcranial magnetic stimulation, magnetic seizure therapy, and transcranial direct current stimulation. Considerable research has provided substantial information regarding their antidepressant and neurocognitive effects, but their mechanisms of action remain unknown. Although the four therapies vary in how they modulate neurocircuitry and their resultant antidepressant and neurocognitive effects, they are nonetheless useful for patients with acute and chronic major depressive disorder and TRD. Continued research is warranted to inform dosimetry, algorithm for administration, and integration among the noninvasive neuromodulation therapies and with other antidepressant strategies to continue to maximize their safety and antidepressant benefit.