a Crisalida, an undulating two-and-a-half-ton tunnel meant to symbolize the Miltown-aided passage to what the painter called “the nirvana of the human soul,” stood in the exhibition hall at the annual meeting of the American Medical Association in 1958, surely one of the more avant-garde exhibits ever to grace a medical convention.
b First synthesized as a blue dye in the 1880s, phenothiazine, chlorpromazine’s parent compound, was over the decades that followed discovered to have an unlikely array of medicinal properties: it worked as an antiseptic (reducing the risk of infection), an anthelmintic (expelling parasitic worms from the body), an antimalarial (combating malaria), and an antihistamine (preventing allergic reactions). Capitalizing on its bug-killing powers, DuPont started selling phenothiazine to farmers as an insecticide in 1935.
c This revolutionized psychiatry. Before 1955, both the acutely psychotic and the moderately neurotic were treated mainly by psychoanalysis or something like it; the working out of psychological issues or childhood traumas in talk therapy was the accepted route to mental health. “No one in their right mind in psychiatry was working on drugs,” Heinz Lehmann would later say of the field before the 1950s. “You used shock, or various psychotherapies.”
d My first glimpse of clinical depression came as I was sitting in class one Friday afternoon that year. I was experiencing my characteristic relief at the prospect of being sprung for the weekend when I had the thought But on Sunday night this starts all over again, and I was chilled by the infiniteness of my plight, by the notion that Sunday nights—and Monday mornings—eternally return, and that only death would put a stop to them, and that therefore there was nothing, ultimately, to look forward to that might help me transcend my dread about bad things to come.
e Yes, it is a mark of the intensity of my phobic preoccupations that I can today, some thirty years later, still remember the conversation almost verbatim.
f Imipramine did more to determine the modern conception of panic anxiety than any other drug. (More about that in the next chapter.)
g Compounding matters, my phobia of vomiting metastasized around this time into a fear of choking; I started having trouble swallowing. (Difficulty in swallowing has been a well-recognized symptom of anxiety since at least the late nineteenth century and is known clinically as dysphagia.) I became afraid to eat. My skinny adolescent frame, worn ever thinner by nervous fidgeting, became emaciated. I stopped eating lunch at school. The more trouble I had swallowing, the more I’d obsess about my trouble swallowing, and the worse the trouble would get. Soon I was having trouble swallowing even my saliva. I’d sit there in history class, my mouth full of spit, terrified that if I were called upon to speak, I would choke on my mouthful of saliva or spew it all over my desk—or both. I took to carrying wads of Kleenex around with me everywhere I went, discreetly drooling into them so that I wouldn’t have to swallow. By lunchtime each day, my pockets would be full of drenched tissues, which would leach into my pants and make them smell like saliva. Over the course of the day, the tissues would disintegrate, so by evening bits of slobbery Kleenex would be spilling out of my pockets.
Are you surprised to learn that I had but one date in all of middle school and high school?
h After trying many alternative remedies, including electroshock therapy, the novelist David Foster Wallace found Nardil to be the most effective treatment for his anxiety and depression. Going off Nardil, after experiencing what seems to have been a tyramine-induced side effect, may have precipitated Wallace’s downward spiral to suicide in 2008.
i Loewi famously claimed he conceived the experiment, which involved artificially raising and lowering the heart rate of frogs, in a dream he had on Easter Sunday 1923. Thrilled, he scribbled the experiment on a piece of paper by his bed—only to awake the next morning to find that he could neither remember his dream nor decipher his own handwriting. Fortunately, he dreamed the same experiment the following night. This time he remembered it, performed it, and demonstrated for the first time the chemical basis of nerve transmission—work for which he would later be awarded a Nobel Prize.
j Otto Loewi and others had found suggestive evidence of neurotransmitters such as norepinephrine in the bloodstream—but no one had yet isolated any in the brain.
k A brief history of early serotonin research: In 1933, the Italian researcher Vittorio Erspamer isolated a chemical compound in the stomach that he named enteramine because it seemed to promote the gut contraction involved in digestion. In 1947, two American physiologists studying hypertension at the Cleveland Clinic found enteramine in the platelets of the blood. Noticing that enteramine caused blood vessels to contract, they renamed the compound serotonin (sero for “blood,” from the Latin word serum, and tonin for muscle tone, from the Greek word tonikos, tonic). In 1953, when researchers for the first time found traces of serotonin in the brain, they still assumed it was merely the residue of what had been carried through the bloodstream from the stomach. Only in the ensuing years did serotonin’s role as a neurotransmitter become evident.
l Imipramine might never have made it to pharmacies—and the history of biological psychiatry might have been quite different—if not for another accident of history. Kuhn’s presentation to the International Congress of Psychiatry was met, as he put it, “with a great deal of skepticism” because “of the almost completely negative view of drug treatment of depression up to that time.” In fact, such was the lack of psychiatric interest in drugs that only twelve people attended Kuhn’s talk in Zurich. (His talk has since been referred to as the Gettysburg Address of pharmacology—little noted at the time but destined to become a classic.) Geigy, too, was unimpressed. The company shared psychiatry’s skepticism about a medicine that could treat an emotional disorder. It had no plans to market imipramine. But one day Kuhn happened to run into Robert Bohringer, a powerful Geigy shareholder, at a conference in Rome. When Bohringer mentioned that he had a deeply melancholic relative in Geneva, Kuhn handed him a bottle of imipramine. Within a few days of starting on it, Bohringer’s relative had recovered. “Kuhn is right,” Bohringer declared to Geigy executives. “Imipramine is an antidepressive.” Geigy executives relented and brought the drug to market.
CHAPTER 6
A Brief History of Panic; or, How Drugs Created a New Disorder
An anxiety attack may consist of a feeling of anxiety alone, without any associated ideas, or accompanied by the interpretation that is nearest to hand, such as the ideas of the extinction of life, or a stroke, or the threat of madness, or the feeling of anxiety may have linked to it a disturbance of one or more of the bodily functions—such as respiration, heart action, vasomotor innervation or glandular activity. From this combination the patient picks out in particular now one, now another, factor. He complains of “spasms of the heart,” “difficulty in breathing,” “outbreaks of sweating,” … and such like.
—SIGMUND FREUD, “ON THE GROUNDS FOR DETACHING
A PARTICULAR SYNDROME FROM NEURASTHENIA UNDER
THE DESCRIPTION OF ANXIETY NEUROSIS” (1895)
The bases of mental illness are chemical changes in the brain.… There’s no longer any justification for the distinction … between mind and body or mental and physical illness. Mental illnesses are physical illnesses.
—DAVID SATCHER, U.S. SURGEON GENERAL (1999)
One day I am sitting in my office reading e-mail when vaguely, at the edges of my awareness, I notice I am feeling slightly warm.
Is it getting hot in here? Suddenly awareness of the workings of my body moves to the center of my consciousness.
Do I have a fever? Am I getting sick? Will I pass out? Will I vomit? Will I, in one way or another, be incapacitated before I can escape or get help?
I am writing a book about anxiety. I am steeped in knowledge of the phenomenon of panic. I know as much as any layperson about the neuromechanics of an attack. I have had thousands of them. You would think that this knowledge and experience would help. And, to be sure, occasiona
lly it does. By recognizing the symptoms of a panic attack early on, I can sometimes head it off, or at least restrict it to what’s known as a limited-symptom panic attack. But too often my internal dialogue goes something like this:
You’re just having a panic attack. You’re fine. Relax.
But what if it’s not a panic attack? What if I’m really sick this time?
What if I’m having a heart attack or a stroke?
It’s always a panic attack. Do your breathing exercises. Stay calm. You’re fine.
But what if I’m not fine?
You’re fine. Every one of the last 782 times when you were having a panic attack and you thought it might not be a panic attack, it was a panic attack.
Okay. I’m relaxing. Breathing in and out. Thinking the calming thoughts the meditation tapes have taught me. But just because the last 782 instances were panic attacks, that doesn’t mean the 783rd one is too, right? My stomach hurts.
You’re right. Let’s get outta here.
Sitting in my office while something like this sequence of thoughts flows through my head, I go from feeling moderately warm to feeling hot. I begin to perspire. The left side of my face starts to tingle, then goes numb. (See, I say to myself, maybe I am having a stroke!) My chest tightens. I am suddenly aware that the fluorescent lights in my office have a strobelike quality and are flickering dizzyingly. I feel a terrible vertiginous teetering, like the furniture in my office is moving around, like I am about to topple forward onto the ground. I grip the sides of my chair for stability. As my dizziness increases and my office swirls around me, my physical surroundings no longer feel quite real; it’s as though a scrim has come between me and the world.
My thoughts race, but the three most prominent are: I’m going to vomit. I’m about to die. I’ve got to get out of here.
I bolt unsteadily from my chair, perspiring heavily now. All my focus is on escape: I need to get out—out of my office, out of the building, out of this situation. If I’m going to have a stroke or vomit or die, I want to be out of the building. I’m going to make a break for it.
Desperately hoping that I’m not accosted on my way to the stairs, I open the door and sprint-walk to the elevator vestibule. I push through the fire door to the stairwell and, with a small feeling of relief at having made it this far, begin to climb seven flights down. By the time I reach the third floor, my legs are quaking. If I were thinking rationally—if I could calm my amygdala and make better use of my neocortex—I would conclude, correctly, that this quaking is the natural result of an autonomic fight-or-flight response (which causes trembling in the skeletal muscles) combined with the effects of physical exertion. But too far gone into the catastrophizing logic of panic to access my rational brain, I conclude instead that my quaking legs are a symptom of complete physical breakdown and that I am indeed about to die. As I descend the final two flights, I am wondering whether I will be able to reach my wife from my cell phone to tell her I love her and to ask her to send help before I lose consciousness and possibly expire.
The door from the stairwell to the outside is kept locked. Motion detectors are supposed to sense you coming from the inside and automatically unlock it. For some reason, perhaps because I am going too fast, they fail to activate. I slam into the door at high speed and bounce off, falling backward onto my rear.
I have hit the door with sufficient force to dislodge the plastic frame around the exit sign glowing red above it. The frame falls onto my head with a thud and then clatters to the floor.
The lobby security guard, hearing the racket, pokes his head into the stairwell to find me sitting on the floor in a daze, the exit sign frame by my side. “What’s going on in here?” he says.
“I’m sick,” I say, and who would say that I am not?
The ancient Greeks believed that Pan, the god of nature, ruled over shepherds and their grazing flocks. Pan was not a noble god: he was short and ugly, ran on stubby goatlike legs, and liked to take naps in caves or bushes by the side of the road. When awakened by passersby, he would issue a bloodcurdling scream that made the hair of anyone who heard it stand on end. Pan’s scream, it was said, caused travelers to drop dead from fright. Pan induced terror even in his fellow gods. When the Titans assaulted Mount Olympus (as myth would have it), Pan assured their defeat by sowing fear and confusion in their ranks. The Greeks also credited Pan with their victory at the Battle of Marathon in 490 B.C., where he was said to have put anxiety in the hearts of the enemy Persians. The experience of sudden terror—especially in crowded places—became known as panic (from the Greek panikos, literally “of Pan”).
Anyone who has suffered the torments of a panic attack knows the turmoil it can unleash—physiological as well as emotional. The palpitations. The sweating. The shaking. The shortness of breath. The feeling of choking and tightness in the chest. The nausea and general gastric distress. The dizziness and blurring of vision. The tingling sensations in the extremities (“paresthesias” is the medical term). The chills and hot flashes. The feelings of doom and gaping existential awfulness.*
David Sheehan, a psychiatrist who has studied and treated anxiety for forty years, tells a story that captures how awful the experience of panic can feel. In the 1980s, a World War II veteran, one of the first infantrymen to land at Normandy on D-day, came to see Sheehan, seeking therapy for panic attacks. Wasn’t the experience of storming the beach at Normandy, Sheehan asked him, bullets and blood and bodies flying and falling all around him—with the prospect of his own injury or death quite real, even likely—more frightening and miserable than enduring a panic attack at the dinner table, however ravaged he might feel by the neurotic circuitry of his own mind? Not at all, the man said. “The anxiety he felt landing on the beaches was mild compared to the sheer terror of one of his bad panic attacks,” Sheehan reports. “Given the choice between the two, he would gladly again volunteer to land in Normandy.”
Today, panic attacks are a fixture of psychiatric medicine and of popular culture. As many as eleven million Americans today will, like me, at some point be formally diagnosed with panic disorder. Yet as recently as 1979, neither panic attacks nor panic disorder officially existed. Where did these concepts come from?
Imipramine.
In 1958, Donald Klein was a young psychiatrist at Hillside Hospital in New York. When imipramine became available, he and a colleague began administering it willy-nilly to most of the two hundred psychiatric patients in their care at Hillside. “We assumed it would be some sort of supercocaine, blasting the patients out of their rut,” Klein recalled. “Remarkably, these anhedonic, anorexic, insomniac patients began to sleep better, eat better, after several weeks … saying ‘the veil has lifted.’ ”
What most interested Klein was that fourteen of these patients—who had previously been suffering from intermittent acute episodes of anxiety characterized by “rapid breathing, palpitations, weakness, and a feeling of impending death” (symptoms of what was then called, in the Freudian tradition, anxiety neurosis)—experienced significant or complete remission of their anxiety. One patient in particular drew Klein’s attention. He would rush in a panic to the nurses’ station, saying he was afraid he was about to die. A nurse would hold his hand and talk to him soothingly, and within a few minutes the attack would pass. This recurred every few hours. Thorazine hadn’t worked for him. But after the patient had been on imipramine for a few weeks, the nurses noticed that his regular panicky visits to their station stopped. He still reported a generally high level of chronic anxiety, but the acute paroxysms of it had stopped completely.
This got Klein thinking. That imipramine could block paroxysmal anxiety without stopping general anxiety or chronic worrying suggested there was something wrong with the prevailing theory of anxiety.
When Freud had hung out his shingle as a “nerve doctor” in the late 1880s, the most common diagnosis among the patients he and his peers saw was neurasthenia, a term popularized by the American physician George Miller Beard to
refer to the mixture of dread, worry, and fatigue that Beard believed the stresses of the Industrial Revolution had produced. The root cause of neurasthenia was thought to be nerves that had been overstrained by the pressures of modern life; the prescribed remedies for these “tired nerves” were “nerve revitalizers”—nostrums such as mild electrical stimulators or elixirs tinged with opium, cocaine, or alcohol. But Freud became convinced that the feelings of dread and worry that he was seeing in the neurasthenic patients he consulted were based not in tired nerves but in problems of the psyche, which could be resolved through psychoanalysis.
In 1895, Freud wrote a paper about anxiety neurosis, a condition he sought to differentiate from neurasthenia and whose symptoms, as he described them, conform quite closely to the DSM-V checklist for panic disorder: rapid or irregular heartbeat, hyperventilation and breathing disturbances, perspiration and night sweats, tremor and shivering, vertigo, gastrointestinal disturbances, and a feeling of impending doom that he called “anxious expectations.”
My Age of Anxiety: Fear, Hope, Dread, and the Search for Peace of Mind Page 22
