From Fever Cure to Coma Therapy: Psychiatric Treatments Through Time

The following is excerpted from Shrinks: The Untold Story of Psychiatry, by Jeffrey A. Lieberman. Listen to SciFri on Friday, May 1, to hear Lieberman talk about the history of psychiatry.

In the early decades of the twentieth century, asylums were filled with inmates suffering from a peculiar form of psychosis known as “general paresis of the insane,” or GPI. It was caused by advanced syphilis. Left untreated, the spiral-shaped microorganism that caused this venereal disease would burrow into the brain and produce symptoms often indistinguishable from schizophrenia or bipolar disorder. Since syphilis remained untreatable in the early twentieth century, psychiatrists searched frantically for any way to reduce the symptoms experienced by a flood of GPI-demented patients, which included mobster Al Capone and composer Robert Schumann.

In 1917, as Freud was publishing Introductory Lectures on Psychoanalysis, another Viennese physician was about to make an equally astonishing discovery. Julius Wagner-Jauregg was the scion of a noble Austrian family. He studied pathology in medical school and then went to work in a psychiatry clinic, where he cared for psychotic patients. One day, he observed something surprising in a GPI patient named Hilda.

Hilda had been lost to the turbulent madness of the disease for more than a year when she came down with a fever entirely unrelated to her syphilis, a symptom of a respiratory infection. When the fever subsided, Hilda awoke clear-headed and lucid. Her psychosis had vanished.

Since the symptoms of GPI typically progressed in only one direction—worse—the remission of Hilda’s psychotic symptoms piqued Wagner-Jauregg’s interest. What had happened? Since her sanity had been restored immediately after her fever subsided, he surmised that something about the fever itself must be responsible. Perhaps her elevated body temperature had stunned or even killed the syphilis spirochetes in her brain?

Today, we know that fevers are one of the body’s oldest and most primitive mechanisms for fighting infection — part of what is known as the “innate immune system.” The heat of a fever damages both host and invader, but it is often more damaging to the invader since many pathogens are sensitive to high temperatures. (Our more evolutionarily recent “adaptive immune system” produces the familiar antibodies that target specific invaders.) Lacking any meaningful understanding of the mechanics of fever, Wagner-Jauregg conceived a bold experiment to test the effects of high temperatures on psychosis. How? By infecting GPI patients with fever-producing diseases.

He started out by serving his psychotic patients water containing streptococcal bacteria (the source of strep throat). Next he tried tuberculin, an extract from the bacteria that cause tuberculosis, and eventually malaria, probably because there was a ready supply of malaria-infected blood from soldiers returning from World War I. After Wagner-Jauregg injected his GPI patients with the Plasmodium parasites that cause malaria, the patients succumbed to the characteristic fever of malaria . . . and shortly afterward, exhibited dramatic improvements in their mental state.

Patients who previously behaved bizarrely and talked incoherently now were composed and conversed normally with Dr. Wagner-Jauregg. Some patients even appeared cured of their syphilis entirely. Here in the twenty-first century it may not seem like a favorable bargain to trade one awful disease for another, but at least malaria was treatable with quinine, a cheap and abundant extract of tree bark.

Wagner-Jauregg’s new method, dubbed pyrotherapy, quickly became the standard treatment for GPI. Even though the idea of intentionally infecting mentally ill patients with malaria parasites raises the hair on the backs of our necks — and indeed, about 15 percent of patients treated with Wagner-Jauregg’s fever cure died from the procedure—pyrotherapy represented the very first effective treatment for severe mental illness. Think about that for a moment. Never before in history had any medical procedure been shown to alleviate psychosis, the most forbidding and relentless of psychiatric maladies. GPI had always been a one-way ticket to permanent institutionalization or death. Now, those afflicted with the mind-ravaging disease had a reasonable chance of returning to sanity—and possibly returning home. For this stunning achievement, Wagner-Jauregg was awarded the Nobel Prize in Medicine in 1927, the first ever for the field of psychiatry.

Wagner-Jauregg’s fever cure instilled hope that there might be other practical ways to treat mental illness. With the benefit of modern hindsight, we might point out that compared to other mental illnesses GPI was highly unusual, since it was caused by an external pathogen infecting the brain. We would hardly expect that a germ-killing procedure would have any effect on other mental illnesses after legions of biological psychiatrists had failed to detect the presence of any foreign agent in patients’ brains. Nevertheless, inspired by Wagner-Jauregg’s success, many psychiatrists in the 1920s attempted to apply pyrotherapy to other disorders.

In asylums around the country, patients with schizophrenia, depression, mania, and hysteria were soon infected with a wide variety of fever-producing diseases. Some alienists even went so far as to inject malaria-infected blood through the skulls of schizophrenic patients directly into their brains. Alas, pyrotherapy did not turn out to be the panacea that so many had hoped for. Though the fever cure mitigated the psychotic symptoms of GPI, it proved impotent against all other forms of mental illness. Since other disorders were not caused by pathogens, there was nothing for the fever to kill, except, occasionally, the patient.

Even so, the unprecedented effectiveness of pyrotherapy in treating GPI shined the first glimmer of light into the darkness that had dominated asylum psychiatry for over a century. Spurred by Wagner-Jauregg’s success, another Austrian psychiatrist, Manfred Sakel, experimented with a physiological technique even more unsettling than malaria therapy. Sakel had been treating drug addicts with low doses of insulin as a way of combatting opiate addiction. Often, heavy users of morphine and opium would exhibit extreme behaviors similar to mental illness, such as relentless pacing, frenetic movement, and disorganized thought. Sakel noticed that when addicts were accidentally given higher doses of insulin, their blood sugar would drop precipitously, inducing a hypoglycemic coma that could last for hours at a time—but after they awoke, they were much calmer, and their extreme behavior had abated. Sakel wondered: Might comas also relieve the symptoms of mental illness?

Sakel began to experiment with artificially induced comas. He overdosed schizophrenic patients with insulin, which had recently been developed as a treatment for diabetes. The insulin overdose put them into a coma, which Sakel ended by administering intravenous glucose. After the patients regained consciousness, Sakel would wait a short while, then repeat the procedure. He would sometimes induce a coma in a patient six days in a row. To his delight, his patients’ psychotic symptoms diminished and they showed apparent signs of improvement.

As you might imagine, there were significant risks to Sakel’s technique. One side effect was that patients invariably became grossly obese, since insulin pushes glucose into cells. A far more permanent side effect was that a small number of patients never woke from the coma and died outright. The most salient risk was permanent brain damage. The brain consumes a disproportionate share of the body’s total glucose (70 percent) despite the fact that it accounts for only 2 percent of the body’s weight. Consequently, our organ of consciousness is acutely sensitive to fluctuations in blood glucose levels and easily incurs damage if the levels are low for any stretch of time.

Rather than viewing brain damage as a liability, advocates of Sakel’s method claimed it was actually a benefit: If brain damage did occur it produced a desirable “loss of tension and hostility,” or so Sakel’s proponents rationalized.

Like fever therapy, coma therapy became widely adopted by alienists throughout the United States and Europe. It was used at almost every major mental hospital in the 1940s and ’50s, with each institution developing its own protocol for administering coma therapy. In some cases, patients were placed into a coma fifty or sixty times during the course of treatment. Despite the manifest risks, psychiatrists marveled at the fact that finally, finally, there was something they could do to ease the suffering of their patients, even if temporarily.

Excerpted from the book Shrinks: The Untold Story of Psychiatry by Jeffrey A. Lieberman, MD. Copyright (c) 2015 by Jeffrey A. Lieberman, MD. Reprinted with permission of Little, Brown and Company.

About the author

Jeffrey A. Lieberman, MD, is the Lawrence C. Kolb Professor and Chairman of Psychiatry at the Columbia University College of Physicians and Surgeons, director of the New York State Psychiatric Institute, and psychiatrist in chief of New York Presbyterian Hospital-Columbia University Medical Center. Formerly the president of the American Psychiatric Association, in 2000 he was elected to the National Academy of Sciences Institute of Medicine. He lives with his wife in New York City.

Author photo by Eve Vagg of NY State Psychiatric Institute