Neurostimulation - An Effective Treatment for Depression?

(Stock photo.)

Neurostimulation broadly refers to using technological devices to deliver electrical pulses to the brain in order to treat patients for ailments such as depression, Parkinson’s, chronic pain and movement disorders, among many others.

Some people have a negative association with these treatments due to depictions in movies of patients being violently subjected to strong electrical shocks while fully conscious during electroconvulsive therapy (ECT) sessions. In reality, ECT actually requires that a patient be placed under general anesthesia, and the intervention can have side effects such as memory loss and headaches. However, it’s a therapy that’s still used today with positive results for patients with severe treatment-resistant depression or other mental or spinal cord disorders. Over the decades, advancements in technology and neuroscience have yielded some promising neurostimulation techniques beyond ECT that could become commonplace treatments for millions of people who suffer from depression or other disorders.

It’s estimated that over 300 million people suffer from depression globally across many demographics, and oftentimes these individuals don’t respond favorably to the standard interventions of medication and psychotherapy. Now, there’s a new form of neurostimulation that can help. 

Repetitive transcranial magnetic stimulation (rTMS) uses an electromagnetic coil to deliver magnetic pulses to a patient’s brain. The short pulses are designed to stimulate the part of the brain that regulates a person’s mood with the goal of relieving depression symptoms. To put it simply, rTMS stimulates the brain’s waves to get them back “in sync.” The sessions last about 30 minutes, don’t require anesthesia, and have side effects that tend to be milder than other forms of neurostimulation. 

Illustration of rTMS device. (Credit: National Institute of Mental Health.)

Transcranial magnetic stimulation (TMS) is an example of a noninvasive form of neurostimulation that differs from other methods such as deep brain stimulation and vagus nerve stimulation, which require devices to be implanted within a patient’s body. According to David McMullen, a neurostimulation researcher at the National Institute of Mental Health in the U.S., noninvasive approaches are being focused on in a number of studies because they have the potential to treat hundreds of thousands of patients as opposed to tens or hundreds of patients as is the case with deep brain stimulation. TMS is one of the most readily available stimulation methods and has clearance from the Federal Drug Administration. Portable TMS devices are currently being considered for approval by Health Canada and would provide patients with the ability to treat themselves at home. 

“There’s been an uptick in the availability of TMS for patients,” said McMullen. “It’s hopefully another tool in the clinician’s arsenal that they can use to help patients. It’s about providing patients with access so that they can get this treatment. Oftentimes patients are treatment-resistant and that might mean that they failed one, two or three medications and maybe psychotherapy doesn’t work. This is an alternative approach.”

A patient undergoes rTMS treatment. (Credit: National Institute of Mental Health.)

McMullen explained that the first generation of rTMS treatment involved delivering 10 Hertz of magnetic electrical stimulation to the dorsolateral prefrontal cortex, and while the treatment has shown some promise to relieve depression, he described it as rudimentary compared to an emerging method. A new version of the treatment offers a more tailored approach to each individual patient by taking into account a person’s unique neuroanatomy. Intermittent theta burst stimulation (iTBS) is a form of rTMS that delivers more rapid pulses to the brain and is thought to accomplish what the 10 Hertz could accomplish in just half the time. Researchers at Stanford University are currently studying the efficacy of theta burst stimulation as part of accelerated intelligent neuromodulation therapy clinical trials. iTBS has been shown to have stronger and faster positive results that rTMS. The Stanford researchers are now studying whether this treatment can induce antidepressant responses in as little as five days. 

“The goal of everything is to take this tool and to improve how the stimulation is specifically delivered,” said McMullen.

Part of the work to improve neurostimulation involves achieving a deeper understanding of how the brain works. A neuroscientist at the University of Ottawa is doing just that by using mathematics to discover how the brain works at the cellular level. The thought is that mathematical models of brain circuits could help illuminate how neurostimulation affects neurons and how those neurons synchronize in order to cooperate in their activities.

As institutions continue their neurostimulation research, some companies are working to push the technology forward to address treatments for a variety of different health conditions. Reports indicate that the market for neurostimulation devices is expected to increase to $11.2 billion by 2026. Last month Medtronic announced that the first patient was implanted with the company’s InterStim Micro system, a rechargeable sacral neurostimulation device to help with urinary disorders. Another medical technology company, Abbott, has a Proclaim system that delivers spinal cord stimulation to treat chronic pain. Salvia BioElectronics raised $31 million to help fund the development of a neurostimulation technology to target chronic migraines. It’s likely that advances in neurostimulation technology to target a particular disorder could spill over into progress on other illnesses.

According to a report from the Medical Device and Diagnostics Industry, over the next five years neurostimulation devices are expected to take a leap forward in efficacy. The idea is that sensors will be able to detect abnormal neurological rhythms, rely on algorithms to determine if stimulation is an appropriate therapeutic response, and if so, deliver the therapy. Such devices would rely on advanced sensing capabilities and enormous datasets of brain function. They would also have to be either implantable or wearable devices that patients could use outside of medical centers.

One of the many challenges to this level of advancement is designing a microelectronic component that can function with the necessary speed, processing power and reliability to enable accurate detection and safe stimulation. Another challenge is that these portable devices must be equipped with small batteries that can store adequate power for operation. One potential solution is to keep the device in “sleep” mode and rely on an algorithm to draw higher power only when needed for stimulation. While this technology may be more applicable to conditions such as epilepsy and Parkinson’s, the portable design could also be an effective method for frequent therapeutic sessions to treat depression or chronic pain. 

“For a patient that goes to a psychiatrist today, being prescribed a course of TMS is a very reasonable approach and has some chance of being helpful to the patient, the same way any medication or psychotherapy may be,” said McMullen. “But we’re always looking to improve that because say 30 percent of patients get better with any intervention, if we can improve that to 40 percent or 50 percent, we can help thousands if not millions of patients. Our goal at the National Institute of Mental Health (NIMH) is to optimize what we currently have and also help the research community and the engineering community develop the next generation of treatments.”

As far as why and how brain waves get out of sync in the first place, that’s still unknown. McMullen said that NIMH is funding and conducting research to better understand the circuit basis of brain disorders. The hope is that the brains of patients who’ve responded well to interventions can be compared to those who haven’t by using functional MRI and EEG. Through this, it’s envisioned that the next generation of therapies can more accurately and precisely stimulate brain regions to bring relief to patients.