Dmitry M. Arbuck, MD President and Medical Director Indiana Polyclinic Carmel, Indiana
Ali A. Farooqui, MD Integrative Psychiatry, PLLC Clinical Faculty Department of Psychiatry University of Louisville School of Medicine Louisville, Kentucky
Rif S. El-Mallakh, MD Professor and Director, Mood Disorders Research Program Department of Psychiatry and Behavioral Sciences University of Louisville School of Medicine Louisville, Kentucky
Disclosures Dr. Farooqui is a speaker for AbbVie and BioXcel. Dr. El-Mallakh is a speaker for Axsome, Idorsia, Intra-Cellular Therapies, Janssen, Lundbeck, Myriad, Noven, Otsuka, and Teva, and has received research support from Sunovion. Dr. El-Mallakh is Current Psychiatry’s Section Editor, Clinical Neuroscience. Dr. Arbuck reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers or competing products.
Neuromodulation may be an effective option for some patients with difficult-to-treat conditions.
While most psychiatric treatments have traditionally consisted of pharmacotherapy with oral medications, a better understanding of the pathophysiology underlying many mental illnesses has led to the recent increased use of treatments that require specialized administration and the creation of a subspecialty called interventional psychiatry. In Part 1 of this 2-part article (“Interventional psychiatry [Part 1]," Current Psychiatry, May 2023, p. 24-35, doi:10.12788/cp.0356), we highlighted parenteral medications used in psychiatry, as well as stellate ganglion blocks, glabellar botulinum toxin injections, and trigger point injections. In Part 2, we review interventional approaches that involve therapeutic neuromodulation and acupuncture.
Neuromodulation treatments
Neuromodulation—the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation, to specific neurologic sites—is an increasingly common approach to treating a variety of psychiatric conditions. The use of some form of neuromodulation as a medical treatment has a long history (Box1-6). Modern electric neuromodulation began in the 1930s with electroconvulsive therapy (ECT). The 1960s saw the introduction of deep brain stimulation (DBS), spinal cord stimulation, and later, vagus nerve stimulation (VNS). Target-specific noninvasive brain stimulation became possible with transcranial magnetic stimulation (TMS). These approaches are used for treating major depressive disorder (MDD), obsessive-compulsive disorder (OCD), anxiety disorders, and insomnia. Nearly all these neuromodulatory approaches require clinicians to undergo special training and patients to participate in an invasive procedure. These factors also increase cost. Nonetheless, the high rates of success of some of these approaches have led to relatively rapid and widespread acceptance.
Box
The origins of neuromodulation
The depth and breadth of human anatomical knowledge has evolved over millennia. The time frame “thousands of years” may appear to be an overstatement, but evidence exists for successful therapeutic limb amputation as early as 31,000 years ago.1 This suggests that human knowledge of bone, muscle, and blood supply was developed much earlier than initially believed. Early Homo sapiens were altering the body—regulating or adjusting it— to serve a purpose; in this case, the purpose was survival.
In 46 AD, electrical modulation was introduced by Scribonius Largus, a physician in court of the emperor Tiberius, who used “torpedoes” (most likely electric eels) to treat headaches and pain from arthritis. Loosely, these early clinicians were modulating human function.
In the late 1800s, electrotherapeutics was a growing branch of medicine, with its own national organization—the American ElectroTherapeutic Association.2 In that era, electricity was novel, powerful, and seen as “the future.” Because such novel therapeutics were offered by both mainstream and dubious sources,3 “many of these products were marketed with the promise of curing everything from cancer to headaches.”4
Modern electric neuromodulation began in the 1930s with electroconvulsive therapy,5 followed by deep brain stimulation and spinal cord stimulation in the 1960s. Target-specific noninvasive brain stimulation became possible when Anthony Barker’s team developed the first device that permitted transcranial magnetic stimulation in 1985.6
Electroconvulsive therapy
In ECT, electric current is applied to the brain to induce a self-limiting seizure. It is the oldest and best-known interventional psychiatric treatment. ECT can also be considered one of the first treatments specifically developed to address pathophysiologic changes. In 1934, Ladislas J. Meduna, who had observed in neuropathologic studies that microglia were more numerous in patients with epilepsy compared with patients with schizophrenia, injected a patient who had been hospitalized with catatonia for 4 years with camphor, a proconvulsant.7 After 5 seizures, the patient began to recover. The therapeutic use of electricity was subsequently developed and optimized in animal models, and first used on human patients in Italy in 1939 and in the United States in 1940.8 The link between psychiatric illness and microglia, which was initially observed nearly a century ago, is making a comeback, as excessive microglial activation has been demonstrated in animal and human models of depression.9
Administering ECT requires specialized equipment, anesthesia, physician training, and nursing observation. ECT also has a negative public image.10 All of these factors conspire to reduce the availability of ECT. Despite this, approximately 100,000 patients in the United States and >1 million worldwide receive ECT each year.10 Patients generally require 6 to 12 ECT treatments11 to achieve sufficient response and may require additional maintenance treatments.12
Although ECT is used to treat psychiatric illnesses ranging from mood disorders to psychotic disorders and catatonia, it is mainly employed to treat people with severe treatment-resistant depression (TRD).13 ECT is associated with significant improvements in depressive symptoms and improvements in quality of life.14 It is superior to other treatments for TRD, such as ketamine,15 though a recent study did not show IV ketamine inferiority.16 ECT is also used to treat other neuropsychiatric disorders, such as Parkinson disease.17
Clinicians have explored alternate methods of inducing therapeutic seizures. Magnetic seizure therapy (MST) utilizes a modified magnetic stimulation device to deliver a higher energy in such a way to induce a generalized seizure under anesthesia.18 While patients receiving MST generally experience fewer adverse effects than with ECT, the procedure may be equal to19 or less effective than ECT.20
Transcranial magnetic stimulation
In neuroimaging research, certain aberrant brain circuits have been implicated in the pathogenesis of depression.21 Specifically, anatomical and functional imaging suggests connections in the prefrontal cortex are involved in the depression process. In TMS, a series of magnetic pulses are administered via the scalp to stimulate neurons in areas of the brain associated with MDD. Early case reports on using TMS to stimulate the prefrontal cortex found significant improvement of symptoms in patients with depression.22 These promising results spurred great interest in the procedure. Over time, the dose and duration of stimulation has increased, along with FDA-approved indications. TMS was first FDA-approved for TRD.23 Although the primary endpoint of the initial clinical trial did not meet criteria for FDA approval, TMS did result in improvement across multiple other measures of depression.23 After the FDA approved the first TMS device, numerous companies began to produce TMS technology. Most of these companies manufacture devices with the figure-of-eight coil, with 1 company producing the Hesed-coil helmet.24
