Coming of Age on Zoloft (7 page)

300.4 Depressive neurosis

This disorder is manifested by an excessive reaction of depression due to an internal conflict or to an identifiable event such as the loss of a love object or cherished possession. It is to be distinguished from
Involutional melancholia
(q.v.) and
Manic-depressive illness
(q.v.).
Reactive depressions
or
Depressive reactions
are to be classified here.
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The language about “reactions” comes from Adolf Meyer, a psychiatrist active in the 1920s and 1930s, who did much to package Freud’s ideas for an American audience. Conditions that would now gain someone a prescription for Prozac were seen by Meyer as maladaptive responses to stressful circumstances, not as illnesses in a biological sense. (Ironically, it’s Meyer who proposed using the word
depression
instead of Freud’s term,
melancholia
; he thought that the latter word implied a level of scientific understanding that we simply didn’t possess, while
depression
—which now sounds like the more scientific designation—was appropriately colloquial.)
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Meyer’s thinking fills DSM-II.

The group at Washington University overhauled DSM-II radically. DSM-III, which they unveiled in 1980, was 494 pages long to DSM-II’s 119. (The trend has continued: DSM-IV, released in 1994, had ballooned to 886 pages, and DSM-5, due out in 2013, is expected to be even longer.) It contained more than two hundred categories of illness. Its tone was completely different too. The brief and impressionistic descriptions of mental disorders from DSM-II had been replaced by long checklists, meant to lead to better standardization of diagnosis. The authors of the new DSM were concerned with the fact, which had recently come to light, that different psychiatrists would often apply different diagnoses to the same individual. DSM-III endeavored to take the guesswork out. If a patient met a certain number of criteria from the list, he or she had the illness—end of story.

Most significantly, DSM-III stripped away all talk of “reactions” and “neuroses.” Its introduction notes tartly that the new manual reflects “an increased commitment in our field to reliance on data as the basis for understanding mental disorders.”
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Since there were no data supporting the idea, for example, that depression was caused by an inner conflict or an excessive reaction to loss, that language was cut. The new manual didn’t put any other causal theory in its place; in general, it remained much more concerned with the “what” of mental illness than the “why.” But by clearing away Freud’s legacy, DSM-III left the field wide open for a new theory to gain hold. And the scientific, medical tone established by DSM-III perfectly suited Schildkraut’s very scientific-sounding amine theory of depression. In that hypothesis was a way of thinking that harmonized with psychiatry’s ambition to shed its humanistic past and enter the fold of modern medicine.

MEANWHILE IN LABORATORIES
in the United States and Europe, research and development work on antidepressants was continuing at its old sleepy pace. In 1972, an Eli Lilly scientist named David Wong and his group in Indianapolis synthesized a molecule that, they realized, inhibited the reuptake of serotonin from the synapses of the brain. But like the original discoverers of Marsilid, they didn’t immediately realize that the new drug could be an antidepressant.
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Though Schildkraut’s amine theory mentioned both serotonin and norepinephrine, most of the neuroscience research on depression to date had focused on norepinephrine. The Lilly company considered marketing its new compound as a blood-pressure medication (serotonin is present not just in the brain but also in the body, where it’s involved in the expansion and contraction of blood vessels). But eventually clinical tests showed that the drug possesssed antidepressant properties, and it went on the market as Prozac in late 1987.

As best I can tell, no one expected Prozac to be a blockbuster drug. But it is clear that this new antidepressant emerged into a very different climate than the one that had greeted Marsilid and Tofranil thirty years before. The language of “neuroses” had been all but expunged from the new DSM, and the “scientific” and data-driven tone it had tried to establish was taking hold. The powerful figures in psychiatry were, increasingly, people who were in favor of seeing
all
mental problems as being ultimately biological in nature. The rise of the “biomedical model” of mental illness, which holds that mental disorders like depression are discrete physical diseases with biological causes, had begun—and Prozac would help it to prevail.

Another recent change made the time ripe for Prozac to succeed in a way that earlier antidepressants hadn’t. Between the 1960s and the 1980s, the tranquilizers had gone out of favor. In 1971, the FDA censured tranquilizer manufacturers for marketing their drugs as treatments for the stresses and strains of everyday life, rather than as a remedy for any specific disease.
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By the end of the decade, stories about tranquilizer addiction had begun to appear regularly in the press, and the public’s love of tranquilizers started to turn into fear and ridicule. For the time being, Americans with minor mental problems were left without a go-to medication.

Prozac was soon followed by other drugs in its family. The SmithKline Beecham company coined the term “selective serotonin reuptake inhibitor,” or “SSRI,” to describe Paxil when it came out in 1993.
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Soon the term was applied to the whole class of drugs, which grew to include Celexa, Zoloft, Luvox, and Lexapro. “Selective” meant that unlike earlier antidepressants, the drug targeted only serotonin, not serotonin and norepinephrine both. The selectivity was supposed to be a selling point, the idea being that a more targeted drug would cause fewer side effects. Interest in norepinephrine’s role in depression gradually faded away. (Only to return: like imipramine, the antidepressant Effexor, introduced in 1993, inhibits the reuptake of both norepinephrine and serotonin, leading some people to call it a serotonin-norepinephrine reuptake inhibitor, or SNRI. Other SNRIs include Cymbalta and Pristiq.)

The antidepressant explosion had begun. As usage of the new drugs stepped up, the biomedical model of mental illness gained currency, as the psychoanalytic model had done before it. Pharmaceutical companies spent millions of dollars on initiatives to educate people about depression; these invariably drove home the message that depression is a chemical imbalance best treated with a drug that acts on chemicals. (As I write this, language on the Zoloft website reads, with a weird mix of precision and vagueness: “Today, it’s widely understood that depression is a serious medical condition. Scientists believe that it could be linked with an imbalance of a chemical in the brain called serotonin. If this imbalance happens, it can affect the way people feel.”
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) In college, I signed up for a psychopharmacology course offered by a new hire in the psychology department; in it we learned about reuptake, looking at diagrams of the lobe-like ends of neurons, with little particles of neurotransmitters bouncing in the clefts between them. Years later, Zoloft’s manufacturer, Pfizer, would launch an advertising campaign that featured homey-looking drawings of the same thing. The first frame pictured two nerve cells, not treated with Zoloft: hardly any globs of neurotransmitter between them. It even
looked
sad. In the next frame, the same two nerve cells, post-Zoloft: neurotransmitters every which way. Fiesta!

Psychoanalysis was out, and psychopharmacology was in. During the 1990s, psychiatrists and ordinary people alike learned to think of a wide variety of mental problems as chemical imbalances, and came to see chemical-balancing medications as the most sensible response. The shift transformed the practice of psychiatry, with analytic methods giving way to a focus on the pharmaceutical management of symptoms that was, indeed, more reminiscent of general medicine than of traditional psychiatry. As if to illustrate just how much things have changed in the couple of generations since the golden age of psychoanalysis, a psychiatrist named Daniel Carlat published a three-page think piece in the
New York Times Magazine
in April 2010, in which he described arriving at a novel idea in his practice: he was going to spend a bit of time during each appointment asking his patients what was going on in their lives, and listening to what they had to say.
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THE PHRASE
“chemical imbalance” sounds great. It conveys a sense of crisp scientific certainty, the promise of detailed technical knowledge about what depression really is. But despite the phrase’s appeal, and its ubiquity, the impression that it gives of open-and-shut understanding is misleading. A scientific model is only as good as how well it accounts for facts, and by that measure, our biomedical model of depression is neither fully complete nor unassailable.

We do know that antidepressants increase the availability of neurotransmitters in the brain. And we know that antidepressants make people with depression feel better (though recent research on the placebo effect shows that these effects might not be as robust as we once believed, particularly for people with “mild” or “moderate” depression
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). But there are still some data that the serotonin-deficiency model of depression can’t account for. For example, studies have shown that only about 25 percent of patients with depression actually have lower than average levels of norepinephrine or serotonin.
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Befuddlingly, while drugs that enhance the availability of serotonin in the brain seem to help alleviate depression, at least one drug that
depletes
brain serotonin has also been found to be an antidepressant—tianeptine, the world’s only selective serotonin reuptake enhancer, is on the market in Europe under the brand name Stablon.
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Some scientists believe that the fact that SSRIs often take several weeks to start working could be a sign that the changes they cause to serotonin levels, which occur within hours of the first dose, trigger other, deeper changes that are actually responsible for the drugs’ antidepressant effect.

While it seems only reasonable to assume that depression, like every other mental state, has a neural substrate, it would be wrong to assume that science has figured out just what this substrate is, or discovered parameters that allow us to distinguish between pathological and nonpathological feelings. Anti-depressants have been shown to improve the moods of people with DSM-diagnosable depression, as well as of people who are merely sad.
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As several psychiatrists pointed out to me, there is no physical test for depression or any other mental disorder. Many clinicians hope and trust that there will be such a test someday—but given that mood is a continuum, the precise spot where “normal” becomes “disordered” will have to be agreed upon, as an act of human judgment. The phrase “chemical imbalance” gestures at the truth, while deftly concealing all that we don’t know, as well as the quotient of subjective reasoning that plays a part in any discussion of mental disorder.

The biomedical model of depression is often spoken about as a challenge to earlier models—as if the illness could be “psychological” or “biological,” but not both. In fact, these interpretations don’t need to be mutually exclusive. The idea that depression is caused by an excessive reaction to the loss of an important relationship and the idea that depression constitutes a malfunction of the serotonin system in the brain could describe two ways of approaching the same phenomenon. It seems only reasonable to assume that our states of mind arise from an interaction of our individual biological tendencies with our life experiences, just as our physical health is the result of a mysterious conversation between our genetic makeup and the treatment we subject our bodies to each day. But instead of expanding on, enriching, and complicating existing knowledge about psychology, our burgeoning understanding of neuroscience has tended to sweep older approaches aside. (Trying to get at this same sense of overcorrection within his discipline, the eminent psychiatrist Leon Eisenberg famously observed near the end of his long career that while psychiatry in the first half of the twentieth century had been virtually “brainless,” psychiatry near the end of the twentieth century had grown virtually “mindless.”)

In fact, some of the most interesting neuroscience research of the last fifteen years does seek to explore the interface of lived experience and biological reality. Work on “gene-environment interactions” examines the complex interrelationships between the environments we live in and the brains that filter them. Researchers like Bruce McEwen of Rockefeller University in New York City have begun to illuminate how environmental factors such as chronic stress can impact the brain (he has found, for example, that just a few weeks of stress can shrink the volume of the brain’s hippocampus, and that a single stressful event can perceptibly change the amygdala), and how both brain-based and environment-based intervention can mitigate them. Such work has led some clinicians to speak of a “biopsychosocial” model of mental disorder, one that appreciates the interrelated contributions of genetic, psychological, and environmental forces. But such blended models face an uphill battle on the road to influence: chemical imbalance is easier to grasp, and pharmaceutical approaches are simpler to implement—and to market—than environmental ones.

While DSM doesn’t formally espouse the biomedical model of depression, it is frequently associated with it. In their book
The Loss of Sadness
, Allan Horwitz and Jerome Wakefield, a sociologist and a social work professor, explore the profound effect that the DSM definition of depression has had on the way that we approach emotional problems. They point out two features that make this definition unique. Most cultures, they write, have recognized a state of sadness so protracted and pronounced that it is best considered not a mere feeling, but an affliction. In most times and places these states have been defined with reference to context: sadness becomes pathological when it is grossly out of proportion with what a situation warrants. Our own society’s definition of disorder was contextual until not long ago. In DSM-II, for example, depressive neurosis is described as an “excessive” reaction of depression; part of the diagnosis was the clinician’s comparison of the patient’s symptoms with what was going on in the patient’s life. But in DSM-III, not only is the doctor not required to take into account what is happening in the patient’s life, but he’s also not supposed to.