During a presentation at Psych Congress 2023 (September 6-10, 2023; Nashville, TN), William McCall, MD, MS, gave a thorough synopsis of neuromodulation and neurostimulation techniques, detailing the circumstances that may warrant their use within the treatment plan for individuals suffering from major depressive disorder (MDD).

In most cases, there are three primary reasons to justify neurostimulation as a method of treatment for patients. These include patient preference, the need for an urgent response, and patients with treatment-resistant conditions, such as treatment-resistant depression (TRD) or even psychosis. The well-known Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study established that a significant percentage of patients may fail to respond to multiple, successive treatment strategies. Some proposed explanations for this are the heterogeneity of MDD, the lack of inter-rater reliability on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, or misdiagnoses. Dr McCall highlighted several examples where depressive symptoms can be better attributed to other diagnoses like bipolar disorder, substance abuse, anxiety disorders, or personality disorders. Physicians must proactively use the tools and screening instruments available to perform a thorough analysis to reach an appropriate diagnosis.

Once confident in their diagnosis, physicians may turn to methods of neurostimulation or neuromodulation to provide rapid relief for their patients, especially in cases where previous approaches have failed. Dr McCall reviewed the currently approved neuromodulating treatments and their respective indications, which vary according to a patient’s diagnosis, age, and medical history. Electroconvulsive therapy (ECT) is indicated for severe TRD, for patients needing a rapid response, and for patients with bipolar depression or catatonia. ECT is also indicated for adolescents. Repetitive transcranial magnetic stimulation (rTMS) is indicated for all TRD with at least one past antidepressant failure. Vagus nerve stimulation (VNS) is indicated for all TRD with a minimum of four previous antidepressant failures, as well as for bipolar depression. Finally, esketamine is approved for all TRD, including patients with suicidal ideations or behavior. Esketamine regulations do not specify a number required for previous antidepressant failures.

Each of these techniques offers a unique combination of benefits and advantages. For example, ECT shows promising results for low risk of cognitive side effects, efficacy in prolonging remission in elderly patients, and preventing depressive relapse; however, it is not specifically approved for this purpose. Perhaps most notably, ECT demonstrates remarkable anti-suicide effects. However, head-to-head comparisons with an appropriate sham ECT procedure are lacking, and no specific mechanism has been defined for this effect. Furthermore, driving is restricted for a day following this procedure. Transcranial magnetic stimulation (TMS), including rTMS, does not require any anesthesia or cause any impairments in a patient’s ability to drive. However, insurance coverage for this treatment is often variable. It involves a lengthy treatment course, and the onset of the antidepressant effects is typically gradual over a period of 6 weeks.  Accelerated TMS programs, such as the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol, are currently under investigation. VNS studies show impressive response and remission rates, but this treatment does involve invasive surgery, the effects can take months to manifest, and insurance approval can be slow.

Some unmet needs remain with the currently available neuromodulating techniques. Fortunately, novel treatments are emerging for the treatment of MDD. Dr McCall outlined several emergent modes of treatment that may provide relief for psychiatric patients in the future. Deep brain stimulation (DBS) is already approved for obsessive-compulsive disorder and offers potential to use depth monitoring electrodes to detect depressive electroencephalogram (EEG) signatures. Transcranial direct current stimulation (tDCS), an instrument often used for ionophoresis, uses a simple 9-volt battery to produce depolarization of large populations of cortical neurons. tDCS shows minimal side effects, and patients can self-administer this treatment at home; however, it is not currently approved for psychiatric disorders, as it is still under investigation.

Overall, neurostimulation modalities offer valuable options for patients with TRD. However, their differing indications, onsets of action, and various disadvantages require additional options. The future is sure to bring some exciting new modes of neuromodulation and neurostimulation, leading to improved outcomes for patients.

Reference:
 McCall W. Advances in neuromodulation and stimulation for the treatment of major depressive disorder. Presented at: Psych Congress; September 6-10, 2023; Nashville, TN