[we come to] learn the incomparable lesson of calm and scientific intelligence, of its systematic application to the improvement of the social conditions and to the refinement of the beauty of the soul and the body. In the harmony of lines and attitudes, the rhythmic grace of gestures, and the balance of thoughts, one would recognize the god of Delos, passing in his chariot, joyful and full of promises.
—Antonio Egas Moniz, Nobel Prize Winner in Medicine for the Lobotomy, on his Journey.
In psychiatry, we spend much time focusing on the side effect profiles because most medicines don't work very well. Unfortunately, that's just the truth.
The unfortunate side effect of this educational and informational approach is that we spend much more time communicating the risks of treatment than the benefits of being well.
We underemphasize the risks of being crippled by a psychiatric illness. We avoid difficult conversations about trade-offs to avoid confrontation with the dangers of a life that sucks. We didn’t start that way.
The Nobel Prize in Medicine has been given to two psychiatric interventions.
The first was awarded to Austrian psychiatrist Julius Wagner-Jauregg in 1927 for his discovery of malaria treatment for neurosyphilis or general paresis of the insane (GPI). The second was awarded to Egas Moniz, the inventor of the controversial lobotomy procedure, in 1949.
The malarial cure for insanity was biohacking at its finest. Treponema Pallium, the spirochete behind the disease syphilis, is a very complex bug. It starts as a sexually transmitted infection but rapidly disseminates throughout the body…and after 20 years or so, it’s drilled enough holes in your brain that you go mad. This is an obvious simplification of a complex host/parasite relationship, but the essential feature about the lil’ Treponema is that they don’t love a sauna. They die above 104 Degrees Fahrenheit. And malaria, well, that causes fevers up to 105.
And 105, well, that’s an autoclave for your neurosyphilis. So by giving people one of the leading causes of “insanity” at the turn of the century, malaria, you equipped them with the ability to generate fevers so high they cured their syphilis.
If this sounds like a horrible idea, it pales before the horrors of late-stage syphilis:
The incidence of neurosyphilis increased significantly during the 19th century and was one of the major factors in the increase of the asylum population during this time. Approximately 5 percent to 10 percent of all psychiatric admissions before 1945 were attributed to neurosyphilis; therefore, these individuals comprised a significant group within the asylum population [13]. In addition, the disease predominantly afflicted middle-class males, and the symptoms were obvious: paralysis in conjunction with dementia or psychosis. Once the patient became symptomatic, the end was near. Death, in most cases, was welcomed as the final respite from the horrifying symptoms of neurosyphilis. Consequently, malarial treatment played a role in the emptying of the asylums and provided a viable alternative for a previously hopeless disease.
It was a moment for biological psychiatry. The second Nobel in Psychiatry continued in this interventionist theme: The inventor of the Lobotomy was Portuguese neurosurgeon Antonio Egas Moniz. The doctor had this to say (translated from his native tongue to English) on the advent of his award with The Nobel:
Intelligence and creative power are always wonderful gifts, but when joined with the spirit of sacrifice and selfless dedication to human happiness, their superior beauty shines with divine light.
Men of science, especially medical scientists, know that truth is elusive and absolute happiness is unattainable, but they spread their wings of thought in an effort to alleviate human suffering. In the chaos of misery and sorrow, they pass like a glimmer of hope, tenacious, anxious, and persevering. For them, for their positive spirit, the general regime of nature is governed by an inflexible order, and no prayer can alter it. Only the perspicacity of their intelligence can reveal to them some partial truths. "They look upon the mystery of things as if they were God's spies."
These innovators were not barbarians, nor were they hucksters. We did not have better treatments. And we needed them. We need them still. There have been few innovations at the scale of “10% of patients cured.” We learned to settle for “half as sick," and the siren song of the provably improved became irresistible. Evidence-based medicine is excellent… until we start asking, “to what standard of evidence must we hold our healing?”
I regularly argue, relentlessly, so much that I should shut up already, that we need a higher standard for what treatment should accomplish for our patients.
The gold standard of “good enough” in scientific research in the treatment of depression has been a 50% reduction in symptoms as measured by a rating scale by a blinded rater to treatment condition, like the MADRS or the Hamilton-D. In schizophrenia, that standard is less still: it’s a 20% reduction in symptoms on the PANSS. Why is it less? Well, it turns out the guideline-making is maddeningly opaque. Without that lower bar, we’d rarely have an approved treatment. So, we lowered the standard. The soft bigotry of low expectations isn’t just a hit line from a Bush-era speech writer; it’s a professional ethos inadvertently.
The flip of a coin is an evidence-based treatment to pass the time. It improves winning a bet when you call “heads” in 2.5% of studies on the topic— if one was foolish enough to believe the statistical chance demonstrated a real difference.
The interventional approaches of the early biological psychiatrists were not effective in the most severely ill patients who have schizophrenia (from John Crilly’s brilliant paper on the history of clozapine):
A number of controversial pharmacologic (e.g., insulin shock therapy) and physiologic (e.g., prefrontal lobotomies) attempts were made to treat symptoms of schizophrenia, none with any notable success. Although the process and results of such interventions were often tragic, professionals working with the most seriously mentally ill during those times had virtually no treatments at their disposal. Pharmaceutical companies, too, had little success in developing medications to treat schizophrenia on a large scale.
We would do well to remember that helping those suffering is difficult—for those trying and failing to help.
To quote Tom Main from 1957, in the classic The Ailment:
“When a patient gets better it is a most reassuring event for his doctor or nurse…cured patients do great service to their attendants…we know that doctors…undertake the work of alleviating human suffering for deep personal reasons and that the practice of medicine, like all human activity, has abiding unconscious determents…we need not be surprised if hopeless human suffering tends to create in ardent therapists somewhat the same gamut of feeling.”
The challenges we set forth to confront with our patients are existential and horrifying at times. Our focus has long been on doing something. But what that something could accomplish needs to be clarified. That something might be a shared expression of the stuckness of a hopeless moment. Absent this, we often descend into the potential sadism of the next thing to do unto another. We do this more often than we might like. We avoid our powerlessness, and, in so doing, relinquish the power of bearing witness to the true.
—Owen Scott Muir, M.D.
Owen, brilliant as always! A couple of considerations. In our field, efficacy describes the potential of an intervention to work in the clinical population, i.e. it's capacity, whereas effectiveness is used to indicate the actual results in the sample of interest. I might suggest that psychiatry is enamored with efficacy actually, in opposition to your thesis, and as such has largely sacrificed a consideration of effectiveness in actual humans living lives of suffering and joy, sometimes at the exact same time. Perhaps if the field spent a bit more time talking to patients with lived experience, engaging in shared decision making around PROs/PREMs, etc that might change? I'd also ask you consider another noteworthy Nobel Prize in Medicine for neurobiology of behavior within psychiatry, that of Eric Kandel, who won in 2000 for work related to the storage of memory in neurons, and is a prolific researcher and writer across the neuropsychiatric spectrum.
It’s the challenge of partially effective treatments that come with serious risks... when dealing with treatment of serious & persistent mental illness, the situation is not unlike non-curative chemotherapy in oncology.