KISSD: Ketamine Intramuscular Stepped System for Depression (eBook)

Chapter 1

The History of Ketamine for Depression

We are lonely and getting more so every day. According to a Time magazine special edition on mental illness, 20,000 American adults reported in a recent Ipsos survey that half of them are painfully lonely some or all the time, while one in four adults deny having friends or family members who really understand them.9 For many of these people, upon the TV has been bestowed the ultimate accolade of best friend. In Asia between 1992 and 2008 a study revealed that loneliness in older folks had doubled from 16% to 30%.

Statistics show that mortality goes up 26% with loneliness, making social isolation a death-enhancing health risk approximately equivalent to smoking and obesity. Loneliness probably exerts its health risk by way of inflammation, which contributes to heart disease, cancer, diabetes and many other diseases. We human beings are social creatures and living without regular contact with companions places us in a constant state of stress.

Our main social organ is the brain. When it is deprived of its fundamental sociality, its response is to go into a stress mode where it spews stress chemicals, alters signaling pathways and enters the stress-slide of anxiety that eventually triggers the black snake of the lateral habenula (LHb) to produce the defining lateral habenula burst mode (LHBM) that is a primary mechanism of depression. 10

Loneliness and its stress are not evenly distributed among peoples in each society. Loneliness seems to be associated with transitions, and as such adolescents and those at retirement age are seeing especially high rates of anxiety and depression. And where teens have smartphones and social media to greatly enhance their statistical numbers of depression and anxiety, old folks have fewer children to keep them engaged, leaving them with high rates of “kinlessness” in a new digital world designed around being alone.

The latest issue of Nature magazine catalogs a progression of anxiety in research graduates that shows that currently 50–75% are suffering significant anxiety. In a 2017 American College Health Association survey involving more than 63,000 students, 61% claimed “overwhelming anxiety,” while almost 41% claimed depression so great that it was difficult for them to function.11 In my own office I query every teen who passes through. I consistently get estimates of 50–90% of their fellow students as suffering from depression and anxiety manifested as the current typical reluctance to look someone in the eye, or the preference to text someone at the same table rather than speak to them, or the morbid preference for their bedroom over teen sociality.

Doctors hold no special answers and are an equal part of the medical problem. At least four hundred doctors a year commit suicide and, as is commonly acknowledged, that rate could be much larger owing to a kind of “cover-up of respect” that seems to attend physician suicide. Where doctors enter medical school with a depression rate reflecting the normal population at 4%, during internship the rate shoots up to 25%, and doctors apparently afford themselves only minimal compassion or care; little treatment is available during the typical medical residency. “Half of all docs are burned out,” says the Time magazine article. 12

There is even a “secret sorrow” suggested at the core of celebrity life, as evidenced by the recent Anthony Bourdain and Kate Spade suicides. Googling recent celebrity suicides resulted in a pages long alphabetized list; narrowing the selection to Anthony’s “B” still gave me twenty-eight other self-inflicted deaths, the first a double death where an actor jumped from a many-storied building while holding her child. Perhaps no place is safe from whatever fundamental menace currently afflicts us. If this is a valid reflection of the disease—and most caregivers I have spoken to think it is—we have a World War II level of concern here and we do not even know who the enemy is.

The October 2019 issue of the New England Journal of Medicine, in an article entitled “Medicine and the Mind: The Consequences of Psychiatry’s Identity Crisis,” reveals that psychiatry has significantly and dangerously departed from the practice of practical psychiatry.

“Psychiatry finds itself plagued by over-prescription of psychiatric medication for a large segment of the population; abandonment and incarceration of people with chronic, severe mental illness; and an increasingly unwieldy diagnostic system of overlapping symptom checklists. Psychiatry should be uniquely positioned to help with this crisis through example, scholarship, and consultation, yet the field seems to have largely abandoned its social, interpersonal, and psychodynamic foundations, with little to show for the sacrifices. There is substantial unmet need for psychiatric treatments and care for children and adolescents, and the emergence of mental health as a priority in the global health arena has increased the role of psychiatry in both international settings and the poorest populations in the United States.” 13

In the article historian Anne Harrington suggests “that psychiatry limit its scope to severe, mostly psychotic disorders.”

What? Limit your scope in the middle of an epidemic? Well, if you are not doing any good, perhaps it is best not to participate. Few professionals believe SSRIs are any kind of valid answer to mild to moderate depression, anxiety or PTSD—SSRIs are clinically effective only in the upper limits of severity. The Star*D trial is often quoted as an example of SSRI antidepressant efficacy and, as such, it is rich testimony to SSRIs’ lack of effectiveness.

For the past 15–20 years of ketamine’s presence on the depression therapy stage, psychiatry has held to a self-serving rule that ketamine should be recognized as a potential treatment only after two or more SSRIs have failed. This rule has always been fraught with self-interest and has kept tens of thousands of suffering patients from a reasonable expectation of relief from their depression treatment with ketamine. Now, evidence has never really been at the core of the constraints placed on ketamine; the problem has always been first the temptation to the money—then the addiction to the billions—that Big Pharma takes in yearly from SSRIs that are doing more damage than good.

With Esketamine’s donation of genuine respectability to generic ketamine, psychiatry’s Hippocratic oath–defying barrier to routine ketamine treatment should be changed.

New rule: no SSRI should ever be initiated for treatment of depression without first failing a trial of the far superior and safer ketamine.

With suicide, anxiety, depression and PTSD all at record levels and increasing in ways we simply do not understand, ketamine is a miracle drug perched at a perfect moment in history to make a difference.

Remaining attached to SSRIs is aptly described by Upton Sinclair’s most famous quote: “It is difficult to get a man to understand something when his salary depends on his not understanding it.” 14

On this note, I would assert that administration of an SSRI before ketamine constitutes a fundamental violation of a physician’s Hippocratic oath if that physician is fully knowledgeable of the actions of these drugs. Reading the quoted Nature article, “Ketamine blocks bursting in the lateral habenula to rapidly relieve bursting,” ought to direct any physician to a proper mode of action. 15 But I am not here to get lost in pointing fingers at vulnerabilities in others’ adherence to their Hippocratic oaths; there’s just not enough time. People are suffering and dying every day from this failing.

Ketamine can make an enormous difference—and is making a difference—for the few who are able to experience its benefits. Less than 1% of the population who could benefit from ketamine has come to know its joys, but its acceptance is growing and its potential for making a difference on the planet is enormous.

Amid this unique, depersonalized loneliness of our modern over digitalized times, John Della Volpe— director of polling for Harvard University Institute of politics— presented disturbing results from polls of 18 to 24-year-old women on the September 20, 2021’s Morning Joe on MSNBC. In the poll, regular Instagram users were noted to suffer relative to nonusers in the categories of self-image—personal and social relationships—depression and hopelessness, and in suicidality-willingness to commit self-harm. Additionally, 10 to 24-year-old females were noted to have suffered an increase in suicidality among less than 25-year-olds of 50% in the years from 2006 until 2018, which amounts to seven thousand suicides a year.

This data—though certainly disturbing—was known; we have noted an increase in disturbed teens for at least the past decade. What was concerning about this event was that recent internal polling from Facebook, recently leaked to the public, allegedly duplicated the results, but had been reported by Facebook as having been positive and healthful. 16

Within the world of depression there is much variation in the administration and accessibility to the drug, which in turn defines its societal effectiveness. Money has been a crucial factor in...