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 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

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