The High-Voltage Quest to Fix the Errant Mind

Major depressive disorder (MDD) affects over 280 million people worldwide and represents a leading cause of disability. Due to the advance of a wide range of psychiatric drugs and psychotherapies, about 60 to 70 percent of patients improve.

The remaining 30 percent of patients do not respond to several trials of drugs and psychotherapy. Their illnesses drag on like long Covid. They are said to suffer from treatment-resistant depressions (TRD) and treatment-resistant schizophrenias (TRS). It is to treat these refractory diseases that psychiatrists, neurosurgeons, and other professionals have come to explore alternative avenues of treatment. Presently, their therapeutic choices consist of anesthetics like ketamine, psychedelics like psilocybin, or various forms of electrical brain stimulation. So, “let’s take a deep dive,” as my grandchildren would say, into this variety of treatments.

Ketamine

Ketamine as an anesthetic was introduced in the 1970s, both in Canada and the U.S. Since then, driven by research into ketamine's effectiveness for treatment-resistant depression and other mental health conditions, ketamine clinics have been rapidly expanding across the U.S. and Canada.

Ketamine may be administered intravenously, intranasally (esketamine), or orally. Multiple recent randomized controlled trials (RCTs) and observational studies confirmed rapid antidepressant and antisuicidal effects (hours to days) of all forms of ketamine, while adverse events were mild and transient. In one study from the University Health Network, Toronto, depression and suicidality scores were significantly decreased after an acute course of ketamine infusions, with improvements persisting while patients continued to receive maintenance infusions over several weeks and months. The authors opined that these results provide preliminary support for the long-term clinical utility of maintenance ketamine infusions.

Psilocybin

A potential paradigm shift for treating a wide variety of mental disorders is the revival of interest in psilocybin in psychopharmacological research.

Psilocybin holds promise for psychiatry, but its successful translation from research to clinical practice demands more robust evidence on efficacy, safety, and methodological rigor. Other factors, such as legal and ethical issues, need to be successfully addressed to facilitate psilocybin’s implementation in healthcare systems.

Electroconvulsive Therapy

ECT, electroconvulsive therapy, first introduced in 1939 in Italy, is still widely used. It is considered one of the most effective therapies for treatment-resistant depression (TRD), with many studies reporting high response/remission rates in 60 to 80 percent of severely depressed patients. Large studies have also demonstrated that ECT reduces suicidal ideation and is associated with lower suicide/mortality.

In each ECT treatment, the patient is given a muscle relaxant and a general anesthetic. When they fall asleep, two metal discs (electrodes) are fastened to their temple. Then a small electric current is passed between the electrodes and through part of the brain that causes a controlled therapeutic seizure, usually lasting 20 to 90 seconds.

Effectiveness varies by technique. Right-unilateral ultra-brief-pulse ECT produces lower remission rates, while conventional bilateral ECT produces higher remission rates.

Unfortunately, absent maintenance medication or maintenance ECT, relapse rates in some centers are up to 50 percent in the first year. Also, a good number of patients complain of minor side effects such as headache, nausea, and muscle stiffness. More troubling is the persistence of confusion, loss of autobiographical memory, and short-term reduction in new learning.

Electrical Brain Stimulation

Now let us switch our attention to electrical brain stimulation (EBS), which, like ECT, entails the application of electrical current directly to the brain by fastening electrodes to the head. The most prominent of these noninvasive methods are transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial random noise stimulation t(RNS), transcranial magnetic stimulation (TMS), and repetitive transcranial magnetic stimulation (rTMS).

An example of a noninvasive EBS technique is repetitive transcranial magnetic stimulation (rTMS), also referred to as magnetic seizure therapy (MST), an approved treatment for adults with depression in many parts of the world. TMS uses a highly focused magnetic coil placed on the scalp to trigger a short, controlled seizure while the patient is under general anesthesia. It aims to produce antidepressant effects comparable to ECT but with greater precision and fewer cognitive adverse effects, as its stronger, targeted magnetic pulses are directed at a part of the brain called the dorsolateral prefrontal cortex, which is commonly implicated in depression. Modern TMS does not require an anesthetic and can be administered in a doctor's office or clinic setting.

An alternative method is transcranial direct current stimulation (tDCS), which has also demonstrated antidepressant efficacy. As with all EBSs, it presents adherence and logistical challenges. To remedy this situation, home-based tDCS, requiring only a flexible cap or band with electrodes worn over the forehead, has been introduced. Evidence suggests that tDCS can be safely administered under remote medical supervision in the home. So, that may be another option where these devices are available.

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The abovementioned methods are all noninvasive. In contrast, the following are invasive in the sense that they require surgical instruments that enter or penetrate the body, often by cutting the skin, bones, and neural tissues. Invasive methods involve direct cortical stimulation (DCS), deep brain stimulation (DBS), and microstimulation.

DBS requires burr holes to be drilled through the cranium, then tiny tubes are inserted through which 1 mm electrodes are passed. These are connected to a very small stimulating device placed under the person’s collarbone, like a heart pacemaker. When successful, DBS may interrupt irregular brain signals that cause depression. The procedure, like every other surgical intervention, carries certain risks: infection, bleed, and hardware problems, plus possible neuropsychiatric effects.

If I were faced with a choice between invasive and noninvasive electrotherapeutics, I would opt for the least invasive.

And one more piece of advice. When looking for a treatment for what ails you, keep in mind that we are all different and that what worked for a friend of yours may not work for you, and vice versa.

This blog is an abbreviated version of an article published in The Globe and Mail, Dec. 26, 2025.