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Authors: Katherine Sharpe

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2
| A Short History of
Medication

F
or a week or more I didn’t notice anything different, just the mood I’d returned to school in, wrapped around me like a heavy blanket. Back on campus I settled into a quiet version of my old routines, but I often felt exhausted, as if once-simple tasks required an effort that was almost impossible to muster. I craved the company of other people, in a diffuse way, but I felt unprepared for the rigors of conversation: my responses to things had to be dredged up from a great depth, it seemed, and inevitably arrived a couple of beats too late. Hiding out in Kate’s room presented a solution. In the afternoons, we sprawled out on her floor with our translations of Plato and Lucretius; around 5:00
P.M.
, we’d carry back something greasy from the dining hall, to eat in the safety of the dark patch of linoleum between Kate’s and her roommate’s beds.

But if I was dull and flattened in one way, I also felt revoltingly attuned in another. Out in the world beyond my few safe places, everything seemed like too much. I felt as if my skin had been removed, leaving me transparent and totally unprotected from the minor radiation of everyday life; every word or glance or impression ripped right through me. If you have ever cried at a movie or a wedding, you know what it’s like to be grasped by a sense of life so big and mysterious that you can’t contain it; it overwhelms you in an instant, and the excess feeling, all that can’t be comprehended, leaks out in tears because it has nowhere else to go. When I was depressed I felt that way about everything, except instead of love and beauty, the excess was sadness, futility, and pain. It was wedding-tears precisely inverted: the presentiment of loss and impermanence that gives happy moments their luminous quality was the central fact, and the presumptive existence of happiness and goodness elsewhere, far away, was what made life seem so unbearably sad.

And so I did cry, at everything. It was as if some emotional pitch detector inside me had broken. Everything meant something, but the meaning was always the same. Even inanimate objects, animals, and trees talked to me about suffering. Sitting by the plate-glass windows in the dining hall, watching a squirrel pick its way across a telephone wire, and wobble, and recover: this was the stuff of high tragedy. In reality, this period couldn’t have lasted for more than a couple of weeks, but in my memory it seems to stretch on forever—a strange little eternity in which shedding tears became a basic bodily function to be fulfilled regularly and by rote, a little pick-me-up squeezed into my hourly, between-class visits to the end-of-row stall in the ladies’ room on the first floor of Vollum Hall.

And then one day, the Zoloft started to work. At first all I felt were some of the side effects I’d been warned about: headache, dry mouth, a new and different kind of sleepiness. A day or two later I stopped crying, just like that. The tragedy I’d been watching came to an unexpected end, and I collected my coat and walked out into the street, surprised to find myself thinking about something other than life, death, the infinite. Not only was I free not to think about them, but for the first time in weeks they didn’t seem any more interesting than anything else: plans for the weekend, say, or conjugating Latin verbs. In the mornings, my stomach rumbled for breakfast.

At first, I studied the medicine’s effects on me with interest. In one sense, they were hard to define. I wasn’t sure how much to credit my improvement to the passage of time, or to being back at school—which, with its many pulls on my time and attention, was an environment much less conducive to brooding than home was. But even allowing for some of that, I feel confident that the Zoloft helped. The change was just too swift and decisive to be completely explainable in any other way.

After a few more weeks I decided that Zoloft was having at least one strange effect. I began to feel less anxious—about everything: not just free of my recent panic, but calmer in every single realm of my life. It was as if some persistent, low-grade undertone of alarm, something so constant that it had never fully registered before, had fallen silent, announcing itself by its absence for the first time. I noticed it most in relation to work; on Zoloft, it became easier than ever before to close the books, say “Good enough,” and declare myself done for the night. But I also felt looser at parties, less self-conscious in the moments before class. I enjoyed the new way of being, but it was peculiar too, and even distressing in its own way. I never thought that I had loved that old anxiety, but it had felt like me. What would I be if not driven? More weeks passed and gave the lie to my immediate fear—that I wouldn’t work as hard, and my grades would suffer—but even afterwards, I held onto the worry that some deep and necessary inner balance might have been shifted, and that the consequences, not that I would ever fully know them, would be bad.

AS I SETTLED
more firmly into feeling better that fall, I began to get curious about my new diagnosis and new treatment. I had an informal sense of what depression was, of course, but I realized, as I thumbed through what I knew, that my understanding was far from complete. I wanted to know what I had, where my medicine had come from, and how exactly it was fixing whatever had gone wrong inside my brain.

I attacked these questions in a way that is typical for me: I started to read. The “Prozac”-titled memoirs just beginning to appear on the front tables at Borders were good for a first course, and by spring semester I was deep into dense university-press tomes with names like
Neuronal Man
and
A Primer of Drug Action
. I found this private research soothing. The idea of having depression made my life feel out of my hands in a way it never had before, and trying to master the topic seemed to go partway towards restoring the missing sense of control.

Sam had upped me to a stronger dose by then, the pills not blue but a pale, pleasant yellow, a color that would have looked right on the walls of a guest bedroom in the country. Some nights I held the capsule in my hand for an extra moment and wondered to myself,
What
is
this thing? What in the hell am I doing?

If you start to read up on depression, one of the first things you’ll learn is that the history of your condition is sprawlingly complex. Part of the reason, it seems, is semantic—depression, or states that we might recognize as such, has been described by doctors and philosophers and ordinary people alike over thousands of years, in terms that sound similar but also subtly different. In the second century
B.C
., the Greek physician Hippocrates described patients suffering from an illness he called “melancholia”; they exhibited despondency, loss of appetite, excessive fear, and difficulty falling asleep. Spiritual writers in England during the Middle Ages spoke of a state known as “acedia” or “wanhope,” which was a disease in one sense, and a sin in another. As the Parson in Chaucer’s
Canterbury Tales
lectures his fellow travelers, the evils of wanhope include “outrageous sorrow,” a crushing sense of guilt and self-loathing, and a dull heaviness “in body and soul,” which if left unchecked can lead to despair of salvation and eventually suicide. Centuries later, the Romantic poets described melancholy as a frame of mind, a mood state that could be exquisitely painful but also beautiful in its own way, a badge of refinement and a source of insight. Freud, like the Greeks, used the term “melancholia”; he meant it to describe a psychological illness that felt like grief, which a person could succumb to after losing an important relationship or possession, or suffering the violation of a cherished value. If melancholia seemed often to descend out of nowhere, he argued, that was because the losses involved were generally subconscious.

Depression, in other words, was like an octopus, sliding through history—recognizable but slippery, undulating and changing shape, its many tentacles in many different pies. It had been described as a physical ailment, a spiritual condition, a temperament, and a reaction to loss. It had been portrayed as normal—something we all go through, to varying degrees—and as profoundly strange, a form of madness. If it was, in some sense, the same thing in all these permutations, you would also have to concede that it was a rangy, diverse, unwieldy thing indeed.

All right
, I thought as I read. This is all very interesting. But surely we’ve come up with something more satisfyingly specific in our day. Surely we have settled by now, against these quaint theories, the question of what depression
really
is?

We certainly had a definition that sounded crisp and definite. In making her diagnosis, I learned, Sam would have relied on a book called the DSM-IV, for
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
. The volume, published in Washington by the American Psychiatric Association, compiled information on all known mental disorders and their symptoms; newspaper articles often referred to it as the “Bible” of psychiatry. The DSM defined depression as the presence “most of the day, nearly every day,” for two weeks or more, of at least five from a list of nine symptoms that included “depressed mood,” “loss of interest or pleasure,” unintentional weight loss, sleep disturbances, psychomotor agitation or retardation, fatigue, feelings of worthlessness, diminished concentration, and thoughts of death or plans for suicide.

That sounded straightforward enough. And according to the DSM criteria, I
had
been depressed, or would have been if my symptoms had rolled on unchecked for a few more days. But where had the DSM definition come from? My attempt to figure that out set me on a path of reading and research that eventually led all the way back to the 1950s. Following it gave me a sense of both how new and unprecedented our current understanding of depression was, and how closely and recursively its rise had been tied to the development of modern pharmacology itself. I learned that though our contemporary definition of depression was specific, it wasn’t, in all its particulars, necessarily any more empirical than Hippocrates’s working definition of melancholia (or, for that matter, any more verifiable than a medieval cleric’s views on wanhope). In short, the story of the Prozac revolution wasn’t a tale of crisp scientific breakthrough. Instead it was a case of science and culture pulling each other along together, our concept of a complicated illness shifting to correspond to our most promising means of treating it. The story of the invention of modern antidepressants and the story of the invention of depression as we know it go hand in hand.

PROZAC WAS BROUGHT
to market in the 1980s, but if it had a family tree, the year “1952” might be carved in near the base of the trunk. On July 5 of that year, a front-page article in the
New York Times
called attention to a medical mystery unfolding on the tuberculosis wards of two New York–area hospitals. Doctors conducting a clinical trial of an experimental T.B. drug called Marsilid had reported that while the new medication didn’t appear to help the patients’ wounds heal, it did seem to have caused a remarkable transformation in their spirits. The doctor in charge told the
Times
that Marsilid induced “a state of euphoria,” which mellowed over a few weeks to “a normally optimistic instead of a depressed attitude.”
1
Though Marsilid seemed to make people healthier, no one could figure out exactly why; tests showed that the patients’ infected tissues were just as clogged with tuberculosis germs after treatment with the drug as they had been before it.

I don’t think I’ll be giving away too much if I tell you that Marsilid turned out to be an antidepressant. But you might think it strange that the doctor didn’t make that leap, even though he used the word
depressed
while gushing to the
Times
reporter. In fact, nobody speculated that Marsilid might be used as a drug for a mental disorder. The
Times
article closed with a lukewarm observation that since the early effects of Marsilid sometimes resembled a “mild narcotism,” the medication might eventually find a niche as a treatment for drug addicts trying to kick the habit.
2

To us today, it seems self-evident that antidepressants would be successful drugs, and valuable ones. After all, depression is everywhere. The World Health Organization identifies depression as the leading cause of disability worldwide.
3
Researchers estimate that depression costs tens of billions annually in lost productivity.
4
The way that Marsilid was received in its day reveals how much our beliefs about depression have changed over the decades. It didn’t immediately occur to the researchers that they had discovered an antidepressant, largely because, sixty years ago, people thought of depression very differently from the way we do now.

It’s not that they didn’t recognize it. In fact, psychiatrists of the time were familiar with two different kinds of depression. One they called “endogenous depression” or “vital depression,” which referred to a profoundly depressed state that was thought to be due to biological causes.
5
Endogenous depression was characterized by insomnia, loss of appetite, psychomotor retardation, and sustained feelings of intense despair: people who had it weren’t just sad, they were afflicted in a patently physical way.
6
But endogenous depression was thought to be extremely rare. Psychiatrists also recognized a more common and often (though not always) less severe type of depression, which they called “depressive neurosis.” Depressive neuroses were not thought to be biological or biochemical in nature, but rather the result of normal psychological processes, like conflict and loss.
7
This everyday depression was spoken about casually, as a diffuse mood state that could arise for any number of reasons, but not as a specific, well-defined ailment of its own. Back then, most depression was more adjective than noun: it was a way you felt, not something you “had” or “were.”

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