What was insulin coma therapy? Dr. Max Fink, the head of the insulin coma unit at the Hillside Hospital in Glen Oaks, Queens, New York from 1952 to 1958, describes the treatment.
Insulin coma therapy (ICT) came to the U.S. from central Europe at the end of the 1930s. It was introduced at the same time as convulsive therapy (ECT, electroshock). These were the first successful treatments for schizophrenia (dementia praecox) at a time when that diagnosis was associated with persistent psychosis, prolonged asylum incarceration, aggressive outbursts, suicide, and dementia.
The treatments were unpleasant and dangerous. They were given without anesthesia. The ICT mortality rate varied from 1% to 10% of patients treated. Prolonged coma, in which the patient did not respond to the administration of glucose, was a constant threat. ECT was safer, with lower mortality rates, but patients suffered fractures, severe memory loss, and spontaneous seizures.
Why did patients and families allow these dangerous treatments to be administered? Indeed, why did families plead for family members to be enrolled in the treatment, even impoverishing themselves to assure ICT at a prestigious hospital? At the time, ICT and ECT were the only treatments that offered the possibility of successful resolution of a dreaded disorder, especially when time alone did not bring about a spontaneous remission.
By comparing these treatments to the treatment of cancer, we can understand their role. For cancer today, the diseased tissue is surgically removed, but if a trace remains, prolonged chemical and radiation therapies become facets of the patient's life. These 'treatments' are life-threatening and debilitating. Nausea, vomiting, hair loss, fatigue, and depression mar daily life. The success rates are poor -- a 5-year remission rate is considered success. Even in the absence of assured success, patients willingly undergo horrendous life courses. So it was with ICT in the treatment of schizophrenia. It was prescribed and accepted when other treatment options had failed.
What is Insulin Coma Therapy (ICT)?
The hormone insulin was discovered in 1922. It was quickly tested in patients suffering with illnesses for which no treatment was known. In Berlin, between 1928 and 1931, Dr. Manfred Sakel used insulin to reduce the anxiety, nervousness, tremors, vomiting, weight loss, and agitation of patients undergoing opiate withdrawal. With insulin, they became calm, gained weight, and were much more cooperative. At times, when the dose of insulin was high, the patient went into stupor. After such events, the patients were less argumentative, less hostile, and less aggressive.
Sakel moved to the University of Vienna, and was assigned to treat patients with schizophrenia, an illness for which no effective treatment was known. He tested the benefits of insulin, reporting that when the patients developed stupor or coma, they lost their psychotic thoughts. His experience was reported to the Vienna Medical Society in January 1933, and by May 1936, favorable reports of the benefits of ICT in schizophrenia from 22 countries were presented at a major meeting of the Swiss Psychiatric Society.
By the 1940s, specialized treatment units were established at the most prestigious private and academic hospitals in America. During the Second World War, both ICT and ECT were approved treatments for patients in the U.S. armed forces.
A standardized treatment protocol was developed. Insulin injections led to two to three hours of low blood sugar levels. (Insulin is a hormone that drives sugars from the blood to storage in the liver.) When blood sugar levels fall precipitously, the brain cannot sustain consciousness and the patients become stuporous. (The sequence of confusion, weakness, awkward walking, slurred speech, and stupor are occasionally seen when diabetic patients have an "insulin reaction," a sharp fall in blood glucose in response to too large a dose of insulin.)
Why the names "Insulin Shock", "Shocks", and "Shock Therapy"?
The German name for the treatment was Insulin-shock-behandlung. Translated into English, the phrase became "insulin-shock-treatment." Sakel interpolated the word "shock" to emphasize his belief that the essential element of ICT was the lowered blood pressure, sweating, increased heart rate, and increased breathing rate that resulted from the stresses produced during the treatment. Extreme stress called forth the body's defenses and he sought to focus interest on the 'shock' aspects as being the therapeutic.
We soon understood, however, that the surgical shock aspects were not important to the treatment results, and emphasis was increasingly given to the coma aspects. The preferred name has been "insulin coma treatment." Reference to the treatment as "shocks" is pejorative, inaccurate, and confusing, and should be avoided.
What is the relation of ICT to ECT, lobotomy, and modern drug treatments?
Convulsive therapy -- the medical induction of seizures for therapeutic purposes -- was first used to treat schizophrenic patients in January 1934 in Budapest. An antagonism between epilepsy and schizophrenia was discerned by the Hungarian neuropathologist, Ladislas Meduna, who found different concentrations of specialized brain cells (glia) in the brains of patients who died with these illnesses. Inducing seizures led to quick improvement, encouraging the widespread use of convulsive treatment. The first seizures were induced with chemicals (camphor, Metrazol). In 1938, the Italians Ugo Cerletti and Lucio Bini showed that seizures could more easily be induced by electricity. Thereafter, electrically- induced seizures, known as ECT, became the main treatment of schizophrenic patients.
Most schizophrenic patients were confined to hospitals, and treated with milieu- and psycho-therapies. Favorable responses were few. When the symptoms became severe, especially when the patients were psychotic, manic, suicidal, or dangerous to others, ECT was given two to three times a week over six to ten weeks. Remission rates varied from 30% to 80% of the patients treated. When ECT failed, ICT was considered. ICT remission rates, in patients who had failed ECT alone, were lower, usually reported as from 20% to 40%. When patients were not improving with ICT, ECT seizures were also induced during the insulin comas.
Lobotomy, a treatment that is often confused with ECT and ICT, is the surgical undercutting of the frontal lobe of the brain. It was developed by Egas Moniz in 1935 for the relief of severe agitation and obsessive-compulsive behavior. It was soon directed to patients with schizophrenia. During the 1940s and 1950s, the three treatments were widely used.
In 1953, an Indian herbal remedy containing reserpine was reported to reduce the agitation and excitement of schizophrenia. In 1954, the synthetic chemical chlorpromazine (Thorazine, CPZ) came to the U.S. from France with observations that it produced a serenity and calmness in psychotic patients that was similar to that achieved with lobotomy. It was quickly hailed as an effective treatment of schizophrenia.
As we had no criteria to decide which treatment, CPZ or ICT, would be best for an individual patient, we sought to answer that research question at Hillside Hospital by randomly assigning patients referred for ICT to either treatment. After treating 60 patients, half with ICT and half with CPZ, we reported that CPZ was as effective in reducing the signs of schizophrenia as ICT, considerably safer, and much less expensive. Our report in the Journal of the American Medical Association in 1958 quickly led to the closing of the Hillside Hospital ICT unit. By 1962, ICT units had closed throughout the U.S.
Dr. Nash's Illness and Treatment Experience
In her book A Beautiful Mind, Sylvia Nasar reports that Dr. Nash first showed the overt signs of schizophrenia in 1959 when he began to see encrypted messages in newspaper stories. He was teaching at the Massachusetts Institute of Technology and after a poorly presented lecture in March, he was involuntarily committed to the McLean Hospital, a private hospital for wealthy patients affiliated with the Harvard Medical School in Boston. He received injections of chlorpromazine but the principal treatments offered were psychotherapy, group therapy, and counseling. After a stay of 50 days, he was released. In May, his wife gave birth to a son. He was not able to return to work, and for the next two years, in the grip of a persistent psychosis, he roamed Europe. Recognizing his brilliance as a scientist, friends arranged a teaching appointment at Princeton University in April 1960. His illness became worse, and in January 1961 he was admitted to Trenton State Hospital, a publicly funded psychiatric hospital.
He underwent 6 weeks of insulin coma treatment. When he was released from the hospital, he was much improved. His thoughts were under control and he was able to once again work on a scientific paper. From July of 1961 to August 1962, he worked at Princeton.
His illness recurred and sadly, further treatment was refused. He spent the next decades as a shadowy figure on the Princeton University campus.
Why was Dr. Nash treated with ICT?
In 1961, the options available for patients with schizophrenia were antipsychotic drugs, ECT, insulin coma, and lobotomy. The optimal treatment was believed to be chlorpromazine, although many psychiatrists still looked to ECT for its benefits. When chlorpromazine failed, ECT was the realistic option. While most psychiatric hospitals had abandoned ICT, it had persisted at Trenton State Hospital, and it was a logical offering when these other treatments were refused. (Lobotomy was no longer a realistic option, having been replaced by antipsychotic drugs.)
If Dr. Nash was offered ECT he may have refused in the belief that it would permanently impair his memory. Medications were offered and either he refused them or he did not respond well. I can easily understand that he might have been turned off by the treatment's restrictions on motor movements, slurred speech, dry mouth, slowing of thoughts, and difficulties in reading. I can easily imagine a man of Dr. Nash's energy and racing mind finding the slowing of his thoughts intolerable.
From the decision to recommend ICT, I infer that Dr. Nash was neither manic nor depressed, refused medications, and was offered ICT because it was the best that was available for his illness. Referral for ICT was a positive development -- he had persistent advocates among the faculty of Princeton for the treatment, as only a few patients could be accommodated.
None of the treatments for schizophrenia, then or today, offer a "cure," in the sense that antibiotics cure an infection or surgery removes a diseased organ; the treatments for psychosis, then and now, are more like insulin for diabetes, a useful management method that is successful so long as the patient continues to take the prescribed medicines. When continued treatments with antipsychotic drugs, ICT, or ECT were refused, Dr. Nash reverted to his psychotic condition.
My Experience with ICT
In January, 1952 I arrived (as a psychiatric resident-in-training) at Hillside Hospital, a free-standing 180-bed psychiatric hospital at the outskirts of New York City. A specialized 22-bed insulin coma (ICT) and electroconvulsive treatment (ECT) unit served about 50 patients with ICT and 130 with ECT each year. At a time when air-conditioning was expensive and rare, the treatment unit was well lit and air conditioned.
The beds were in two rows. Between the beds were stands for equipment and supplies. The beds and bed-stands were metal coated in white ceramic. The beds were framed with side-rails. Two physicians (sometimes three), four nurses, and an equal number of aides were in attendance. Treatments were given every week-day morning. Nurses wore white, well-starched uniforms, and doctors wore white coats, white shirts, and ties. (Since long ties occasionally became soiled by blood, I took to wearing bow ties -- a habit that persists until today.)
Like McLean Hospital, Hillside Hospital prided itself on the use of psychoanalytic, group, and milieu therapies, and was considered a premier treatment and training center. It had an active and well-regarded residency training program. In 1954, it developed a research department that flourishes to this day. ICT and ECT were the secondary treatments offered patients when they were not amenable to psychotherapy. In the hierarchy of treatments, ICT was the last resort.
What did a patient experience in ICT?
He was awakened at 0600, dressed in cotton shirt with short sleeves, and long drawers. No food was given. Taken to the ICT unit and assigned to a bed.
Temperature, blood pressure, and heart rate were recorded. An intramuscular or (occasionally a subcutaneous) injection of insulin was given (usually in a shoulder or buttock, in rotation). Insulin was withdrawn from a vial with a rubber top. Dosage had been assigned the day before.
Stages of Coma
Patient went gradually to sleep and then to coma. Two forms of coma were recognized, a "wet" and a "dry." In the "wet" form, sweating was profuse and was accompanied by "goose-bumps" in the skin. Salivation increased, so much so that nurses sopped it up with gauze sponges. In the "dry" form, the skin was hot and dry, muscles twitched, in a sequence that began in the face, arms, and then in the legs. These were often small twitches, but from time to time, patients would move and jerk an arm or a leg. Occasionally, a grand mal seizure supervened.
Patients sometimes complained of being chilled, and blankets were usually placed as covers.
While most patients were sedated, some became excited. Restraints were applied (usually a bed sheet folded in quarters and tucked under the mattress).
0715-0745: Stage-1 coma.
Patients no longer responded to voice or to touch. The Babinski test, an abnormal neurological sign, became positive. (The doctor would stroke the outer part of the sole of the foot, from heel to outer two toes, and look at the movement of the big toe. A "normal" movement of the toe is downward. A "positive Babinski sign" is an upward movement of the big toe. This indicates that the "higher" brain functions are impaired.)
0745-0830: Stage-2 and Stage-3 coma.
Breathing became slow and stertorous. Eye movements wandered. The pupillary response to light was still present. Occasional spasms of the main body muscles were seen. Sweating was severe, and temperature rose.
In time, breathing became irregular, pulse rapid, and corneal and pupillary reflexes absent. Deep tendon reflexes were lost (striking knee gets no knee-jerk and shining a light gets no pupillary reaction).
Coma stages were checked every 10 minutes. The time of stage-2 coma was noted. The coma was ended from 30 to 60 minutes later, according to the doctor's prescription.
How was the coma ended?
Administering glucose ended the coma. Most often, a "gavage" tube (a thin rubber tube) was placed through the nose into the stomach. The nurse would then administer between 200 cc. and 300 cc. of 50% glucose solution.
A second method was the intravenous administration of 25 cc to 50 cc of a 10% glucose solution. In both methods, patients would awaken quickly.
What was the patient's experience on awakening?
When a patient became conscious, his responses would be slow, with a thick (drunken) speech. Within 15 minutes, he recognized the nurse and doctor, knew where he was, and asked for breakfast. He was very wet; often the bed was soiled. He was taken to a recovery room, showered, and allowed to dress in ward clothes.
Patients were fed their breakfast either in the treatment room or on the ward. Patients ate avidly. It was commonplace for patients to gain considerable weight during the months of a treatment course.
Recollections of thoughts and anxieties were reduced. Patients became calm, less concerned about delusions and hallucinations (these disappeared in successful treatments), and approached their families in a more friendly manner. Those who had been excited and needed restraints, no longer required them.
Patients spent their days reading, meeting with family, or taking part in the hospital routines. Some patients exhibited a silly laughing or crying, without regard to the immediate experience. Transient neurological signs -- weakness of an extremity or errors in speech (aphasia) -- were common. Memory of the illness and recent public events became less clear, but patients retained good recollections of personal memories.
Recovered patients returned home to their work and to their families. For those who had minimal to moderate relief, further treatment with antipsychotic drugs or ECT was prescribed.
The response of Dr. Nash -- immediate relief with the treatment, return to work after an illness of three years, and then gradual relapse followed a common pattern. For a few lucky patients, the treatment worked well and patients returned to a normal life.
Insulin Coma and Seizures
For insulin coma, Sakel rejected spontaneous grand mal seizures as unwanted, unpleasant, and unnecessary. Seizures did occur during ICT, appearing in the second and third stages of coma, especially during periods of "dry coma." Two schools of thought developed -- those who saw seizures as comparable to the seizures of ECT and therefore favorable for a better outcome, and those who considered seizures as unwanted side-effects.
A spontaneous seizure called for protection of the patient's tongue and mouth, as well as restraint. (Every bed-stand had special tongue guards available to be used when a spontaneous seizure developed. These were wooden tongue depressors, about pen-length, 1/2" wide, covered at one end by gauze, or cotton and gauze, to make a soft mouthguard. Or, rubber-tubing doubled and covered by gauze to make a mouthguard.)
By the 1950s, when a patient in ICT was not improving by 20-25 comas, some physicians augmented ICT by ECT given during the deep coma period, usually at three times a week. (I was taught, and taught others, and still believe, that seizures augmented the benefits of ICT. A spontaneous seizure in ICT was welcomed, and not seen as a bad sign.)
Spontaneous grand mal seizures were infrequent. Muscular twitching, jerking of the extremities, grimacing of the facial muscles, and tortuous twisting movements of the limbs and body were frequent. These occurred in the early stages of the treatment.
How do we understand the mechanism of action of ICT compared to modern treatments for schizophrenia?
The immediate benefits of ICT were increased feelings of well-being and less preoccupation with obsessive thoughts. Weight increased and agitation decreased. For many patients, these benefits were sufficient to allow them to return to home and community. It was unclear then, and remains so today, what mechanism could explain the relief of psychosis.
We do not know why schizophrenia develops in adolescence, why it persists, nor what is the pathology in the brain that has gone awry. In animal studies, modern medicines affect the brain's neurohumors (such as serotonin, dopamine, and adrenaline). Many scientists believe that aberrations in these systems are the cause of schizophrenia, and see the medicines as redressing hypothesized abnormalities. Such theories are not supported by human research.
When ECT and ICT were introduced, much academic interest was focused on the brain's electrical activity as measured by the electroencephalogram (developed in 1929). Measurement of the brain's electrical activity during courses of ICT showed dramatic and persistent changes. Amplitudes of the brain rhythms increased, frequencies slowed, and new patterns of spike and slow burst activity appeared. When these brain changes did not develop, the patients did not improve. The benefits of ICT were best assured when the brain's electrical activity changed, and this occurred most often after a prolonged coma. The benefits in ICT were seen to be in developing new (different) brain rhythms of electrical activity that did not encourage psychotic thoughts. Similar observations were made in support of a neurophysiologic theory for ECT.
Different ideas of the mechanisms of action of these treatments come from the roles of the brain's neuroendocrine processes. The body's functions are monitored by chemical substances (hormones) discharged from such specialized glands in the body as the adrenal, thyroid, parathyroid, pituitary, ovary, and testis. These glands are controlled by the brain's neuroendocrine glands, the hypothalamus and the pituitary. The substances are discharged in cyclic fashion, with cycles that are a day, month, and lifelong in duration. The substances determine the diurnal cycles of waking, sleeping, and eating; periodic cycles in sex; and life.
In patients with psychiatric disorders, the hormonal regulations have gone awry. The best example is in major depression where the hypothalamic-pituitary-thyroid-adrenal interactions are grossly abnormal. With effective treatment, as with ECT, these imbalances are normalized. (And when the illness recurs, the imbalances have returned.)
Insulin is a very powerful stimulant of the endocrine and the neuroendocrine systems, as is the coma produced by it. It is probable that insulin coma's benefits may have been achieved by redressing hormonal imbalances, in a fashion similar to that of ECT. (During the ICT era, we did not have the knowledge of neuroendocrine interactions nor the methods of study that we have today.) Such actions would also explain the benefits achieved when ECT was added to ICT.
Many forms of schizophrenia are identified, labeled as the paranoid, catatonic, hebephrenic, simple, etc. ICT was most effective in patients with the catatonic form, less so with the paranoid, and least with the other forms. Interestingly, the hormonal imbalances are most prominent in patients with catatonic schizophrenia, and less so in the other forms.
These Treatments Today
Today's main treatment of patients with schizophrenia is the prescription of antipsychotic drugs. These offer control of symptoms but rarely offer a cure.
ICT is no longer practiced in the West. Reports of its continued use in the former Soviet Union and in China occasionally appear.
Lobotomy, sometimes called leucotomy or psychosurgery, is occasionally used to relieve patients of agitation and severe obsessive-compulsive rituals -- the patients for which it was first advocated.
ECT is now widely prescribed for the relief of severe psychiatric illnesses. We have learned, to our disappointment, that none of the medications used for the treatment of psychiatric illnesses provide "cures." A percentage of patients quickly become "therapy resistant." The medications fail to control their psychosis, and it is at such times that ECT is widely employed today.
Max Fink, M.D.
William Karliner, M.D.
Dr. Fink was in charge of the insulin coma unit at the Hillside Hospital in Glen Oaks, Queens from 1952 to 1958. He has had an academic career in research and teaching of neuropsychiatry with more than 600 scientific publications and numerous books. The latest is Catatonia: A Clinician's Guide to Diagnosis, Treatment and Neurology (Cambridge University Press, 2002). He is an emeritus professor of Psychiatry and Neurology at the State University of New York at Stony Brook.
To assure accuracy, this draft was edited by Dr. William Karliner, a neuropsychiatrist who introduced insulin coma therapy to the U.S. Dr. Karliner is an emeritus faculty member of the Albert Einstein College of Medicine.