Zapping Depression

“Ultimately we’re trying to get into the brain and tickle neurons,” said Medical University of South Carolina neurologist Mark George about his specialty — using electricity-based treatments to modify brain function. For treating depression, neuromodulation has become increasingly mainstream—including ECT (electric shock therapy) and new protocols for TMS (transcranial magnetic stimulation).

Whatever kind of energy is used—magnetic pulses, ultrasound, infrared light—“brain cells translate it into electrical impulses [that] travel from cell to cell,” writes Rachel Gross in The New York Times. “Electricity is the brain’s lingua franca.”

Electrical methods may work better than medication, which focuses on altering the brain’s chemistry. Given the discovery that impaired neural connectivity plays a role in depression, Gross explains, neuromodulation could boost signals from those neurons that help “the depressed brain to work better overall.”

Compared to magnetic stimulation, electroconvulsive therapy (ECT) delivers high levels of direct electrical currents under anesthesia to induce brief seizures and is considered the most effective use of electricity for treatment-resistant depression (TRD). Side effects include memory loss, but refinements over the years have brought ECT a long way from the horrifying experiences recounted in literature and film. An alternative, direct transcranial stimulation (tDCS) employs very low amounts of electricity and has performed less successfully.

Ketamine, originally used as an anesthetic, has become another burgeoning treatment for depression, and is now available as an infusion or nasal spray. But these newer treatments remain out of reach for most people, due to high costs not yet covered by insurance and the need for repeat treatments. Also, many people have unpleasant physical and mental sensations both during and after TMS, ECT, and ketamine treatments, causing them to quit after their first try. While research has shown positive success rates, most sample sizes are small and improvement is hard to measure.

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Variations in how each person’s brain works help explain why depression often persists despite repeated attempts at treatment. Writes cognitive neuroscientist Mark Allen on Cognitivefx.com, “A reanalysis of the largest antidepressant study conducted revealed a remission rate of only 35% after patients had tried four different antidepressants. Also, antidepressant medications may take 6 to 8 weeks to show results, and patients often need to try multiple medications before finding an effective one.”

“I believe in electricity for the body,” retired international lawyer K.K., who struggles with debilitating TRD, wrote in an email. Inspired in part by The Body Electric: Electromagnetism and The Foundation of Life by New York orthopedic surgeon Robert O. Becker, K.K. wears electrical muscle stimulation (EMS) devices while exercising to boost muscle development, and uses infrared LED face masks for skin care several times a week.

After decades of failed treatment for her TRD, K.K. underwent a two-week psychiatric evaluation that led her team to suggest trying either ECT or a TMS five-day intensive protocol developed at Stanford University. Choosing SAINT (Stanford accelerated intelligent neuromodulation therapy), K.K. received bursts of theta waves—brain waves observed during meditation and some phases of sleep—every 10 minutes over 10 hours each day.

Before beginning treatment, functional MRI scans pinpointed the location of brain areas that appear under-active in depression, called the DLPFC (dorsolateral prefrontal cortex). “Downstream effects” occur in other brain structures, such as the amygdala. Said Stanford psychiatrist Alan Schatzberg, co-author of the original SAINT research, “It’s quite a dramatic effect, and it’s quite sustained.”

In the original Stanford study of 29 people with TRD, about half received placebos; of those who had the SAINT protocol, 78.6 % of patients were “no longer depressed.” According to a 2020 blog post from Harvard Medical School, “Around half of patients who have failed to benefit from multiple antidepressant medications experience a clinically meaningful response [with traditional TMS].” But “Only about one-third of these individuals experience a full remission, meaning that their symptoms go away completely. [Also] these results, while encouraging, are not permanent… there is a high recurrence rate.”

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Despite years of experience with TMS, uncertainties remain about which brain areas play a role in depression and is crucial to placing the coil that delivers magnetic pulses. “Clinicians must find the treatment target area consistently and reliably for every treatment session,” according to several neurosurgeons in a 2023 Frontiers overview article. “If the functional networks affected by these approaches were better understood, a theoretical basis for selection of interventions could be developed to guide psychiatric treatment pathways.”

In the weeks following her SAINT TMS treatment, K.K. observed no benefits. In a subsequent consultation, a different psychiatrist advocated talk therapy but also told K.K. about “encouraging” results with ketamine. For depression, ketamine treatment usually begins with a series of 3-6 IV infusions over several weeks, with the goal of disrupting negative thought patterns. MRI scans of patients’ brains following ketamine infusions have shown changes in cerebral blood flow linked to alterations in functional connectivity.

In a recent evaluation, Thomas Insel, past director of the National Institute of Mental Health, called ketamine, “The most important breakthrough in antidepressant treatment in decades.” Over the past 10 years, clinics offering ketamine infusions for mood disorders have multiplied around the U.S.; the FDA has also approved the use of ketamine in a nasal spray, called esketamine.

While aware of the challenges in treating any condition of the brain, I find the failure of depression treatment for so many people to itself be depressing. I despair for close friends struggling with debilitating depression and others who experience bouts of depression on a regular basis. I have taken antidepressants and tried different therapies, making me grateful to have many options to try — though uncertain what helped the most. Participating in a therapy group for about five years took me through a difficult transition, but the two new friendships that have lasted years might be its greatest gift.