In 1985, I was at a friend’s wedding reception when a woman I’d known in college told me that she was so sorry about my baby, and that she’d heard I’d had a nervous breakdown. Embarrassed, I replied no, it was clinical depression. She was a medical student at the time, and I figured she would know what that meant. It was a term I’d begun to rely on since my discharge a year earlier, though it didn’t seem to express the extremity of what I had been through. In saying that I hadn’t had a nervous breakdown, I was pushing back against the idea that a failure of nerves had been my problem.
It may be hard to believe, but as recently as the mid-1980s, depression as an illness hadn’t made much of a mark on the public consciousness. The catchall term “nervous breakdown” was a remnant of earlier decades, when it served as a euphemism for any sort of collapse that might necessitate a period of social withdrawal, absence from work, or even a timeout in a psychiatric facility. Nervous exhaustion, mental illness, alcoholism—all huddled with a blush of shame under the word “breakdown.”
Barely a decade later, “depression” was everywhere. And as the century came to a close, the sheer numbers of people taking antidepressants made it look like an epidemic. The timing of my diagnosis, in the mid-eighties, meant that I belonged to a generation of depressive patients who would become the subjects of a mass experiment. We would shift from the most commonly used older medications—the tricyclics, which were well-known and proven effective—to a new type of drug whose qualities, dangers, and long-term effects were as yet unclear. These were the SSRIs, selective serotonin re-uptake inhibitors, of which Prozac was the first. And we would be joined in taking these new drugs by many people who had never seen a psychiatrist; the majority of antidepressant prescriptions would soon be written by general practitioners. To understand the scale of this revolution, consider that in 1975 only 4 percent of Americans had ever taken an antidepressant, and total sales for the year amounted to no more than around three hundred million dollars. In 1995, just seven years after its introduction, sales of Prozac alone reached two billion dollars. Within twenty years of Prozac’s arrival, by 2008, the number of Americans using antidepressants had risen by 400 percent. Now, depression is “the common cold of mental illness.” What could account for so dramatic a change, and in so short a time?
In retrospect, it’s clear that a single drug—Prozac—looms large, and so does the third edition of the so-called bible of psychiatry, the DSM-III, which arrived in 1980 with a totally reconceived approach to naming and diagnosing disorders. Between the two, the result was a broader definition of depression and far greater public attention, with an assist from pharmaceutical marketing, to identifying and treating the disorder. If, like me, you have a diagnosis and you take medication, you’re probably aware that while doctors provide diagnoses and write prescriptions, they may not have the time to explain why your old medication has become outmoded and why something new is worth a try. Does the new drug represent real progress, or is it merely a marvel of successful marketing, channeled through your doctor? Rather than ask questions, you fill the prescription and hope for the best. While to summarize what has changed since 1980 it is necessary to oversimplify, I’ll share some of what I’ve found useful to know, along with the account of my own struggle to come to terms with the benefits and limitations of medication.
THE SEARCH FOR effective ways to treat psychiatric disorders has historically been rooted in two central questions. The first—Is the cause of symptoms to be found in the patient’s body?—points to a quest for the physiological processes that underlie dysfunction, and is the focus of the biomedical approach. The second—Is the cause of symptoms in the patient’s life?—points to an effort to locate the sources of conflict or stress in the patient’s experience, past or present, and is the focus of the psychodynamic approach. The first seeks to treat the body; the second, to treat the person. In the twentieth century, a power struggle between these two modes of thinking shaped the profession’s models for diagnosing and classifying illness and, in turn, the lives of the innumerable patients they treated.
The historian Edward Shorter comes down firmly on the side of the biomedical camp when he writes, “It is Kraepelin, not Freud, who is the central figure in the history of psychiatry.” In America, the pendulum swing of twentieth-century psychiatry moved from Kraepelin to Freud and then, with DSM-III, back again. Emil Kraepelin, who was born in Germany in 1856, just three months before Sigmund Freud was born in Moravia, began his career working in asylums and tending to patients with the most serious forms of mental illness. He made a systematic study of his patients’ courses of illness over as many years as he could follow them, creating a card for each patient and listing an initial diagnosis, then revising the diagnosis over time. If the patient was discharged and later returned, Kraepelin would again note changes on the card. His notecards, over the years, began to suggest a taxonomy of illnesses and their probable course and outcome. He was able to see that a psychosis in young people, which he called dementia praecox, was a distinct disease, probably biological in origin. Kraepelin then divided the known mental illnesses into two groups: those without and those with an affective—emotional—component. These, in today’s parlance, are the mood disorders. He developed and modified his thinking in the nine successive editions of his textbook, the Compendium der Psychiatrie, from 1883 to 1927.
Kraepelin brought three major mental illnesses into clearer view: schizophrenia, and what we now know as bipolar and unipolar depression (he saw these as two different manifestations of a single disease, which he called manic depressive insanity). Melancholia was present in both, but Kraepelin had seen manic states develop in some depressed patients and not in others. In both types he recognized periods when the illness seemed to resolve itself, only to return. Today, major depression and bipolar disorder are categorized separately in the DSM and require different treatment, but since their genetics and biological underpinnings appear to be closely related, Kraepelin may have been correct in seeing them as different expressions of the same disorder.
Kraepelin set in place the medical model of psychiatric diagnosis, emphasizing that “it is disturbances in the physical foundations of mental life which should occupy most of our attention . . . disturbances of comprehension, memory and judgment, illusions, hallucinations, depression, and morbid changes in the activity of the will.” He founded the department of psychiatry at the University of Munich, and his efforts led to the opening in 1917 of the German Institute for Psychiatric Research, where scientists gathered to work on brain anatomy, genetics, and metabolism, hoping to discover the physiological underpinnings of mental disturbance. And he refused to take into account Freud’s theories about the causes of those disturbances, because he saw in psychoanalysis no basis in science.
In America, Kraepelin’s medical model proved influential at the critical moment when the association of asylum psychiatrists—the forerunner of the American Psychiatric Association—created a handbook of psychopathological conditions in 1918. It was called the Statistical Manual for the Use of Institutions for the Insane and listed twenty-two diagnostic categories, nearly all of which presumed, as Kraepelin had, the presence of organic brain dysfunction. But over the next few decades, with hard evidence of brain disease still elusive, the perspective from the asylum receded. Psychiatrists increasingly turned to Freud’s psychogenic theories to explain disturbances of thought and behavior.
In America, this shift was largely the work of the two influential psychiatrists, Adolf Meyer and Karl Menninger, who shared Freud’s belief that mental illness and health existed on a continuum. The Swiss-born Meyer, who became a professor of psychiatry at Cornell and later headed the Scripps Clinic at Johns Hopkins, was for several decades a figure of tremendous authority. In 1921 he was asked to speak at the centennial celebration for the Bloomingdale Hospital in White Plains, where I would eventually be treated, and where Meyer’s influence could still be felt. In that speech, he emphasized his belief that the “life problems” of individuals put “their mind and the entire organism and its activity in jeopardy.” Mental disorder was a maladaptive reaction of the mind, body, and personality to life situations. One harmful extension of this approach, the “refrigerator mother” theory of the 1950s and ’60s, proposed that autistic children were socially withdrawn because their mothers were emotionally cold. Autism, in other words, was a reaction type, psychological rather than neurological.
One of the first American psychiatrists to receive psychoanalytic training, Karl Menninger called himself “more Freudian than Freud.” Along with his father and brother he founded the Menninger Foundation and Clinic in Topeka, where thousands of students were trained in the principle that psychiatric illness resulted from the failure to adapt to one’s environment. Environmental stress—war, an unloving family, poverty, social oppression—could cause psychoneurosis and, in more severe cases, psychosis. Instead of focusing on the clinical differences between types of illness, he wrote, “we propose to think of all forms of mental illness as being essentially the same in quality, and differing quantitatively.” A case of melancholia, for instance, differed from mild depression in degree, not in kind. The psychiatrist’s task, Menninger stated, was to reveal “how the observed maladjustment came about and what the meaning of this sudden eccentricity or desperate or aggressive outburst is. What is behind the symptom?”
The American Psychiatric Association officially enshrined the lineage of Freud, Meyer, and Menninger in the first two editions of its Diagnostic and Statistical Manual—DSM-I appeared in 1952 and DSM-II in 1968—where categories of disorder included various types of reaction and neurosis. The APA also recommended that all psychiatrists should be trained in Freudian and psychodynamic concepts, and psychoanalytic training institutes began to spring up in major cities. Psychoanalysts chaired the psychiatry departments at most universities and held the medical directorships of most psychiatric hospitals, including the one where I would be treated. Research into the physiological basis of mental illnesses had languished for decades, as had any real interest in refining and clarifying the task of diagnosis. Most psychiatrists chose to treat patients with relatively mild emotional disturbance in private practice, rather than the more desperately ill patients found in psychiatric hospital wards. For those who did attempt to treat psychotic patients with psychoanalysis, things could go very badly.
So matters basically stood until the 1970s, when psychiatry found itself facing a crisis of legitimacy. Thomas Szasz, a leader of the growing antipsychiatry movement, cast doubt on the validity of diagnostic categories. In a debate on the question “Is Depression a Disease?” Szasz pointed out that depression is not included in pathology textbooks. “Show me the pathology,” he demanded, disregarding the reality that, at the time, pathology in the brain was difficult to confirm without an autopsy. Sociologist Erving Goffman, psychiatrist R. D. Laing, and others pressed the case against psychiatry as well, arguing that diagnoses were more often labels of social deviance than of real illness. In 1973, gay activists proved that to be true when they won their campaign to have homosexuality removed from the DSM-II, where it had been listed among the sociopathic personality disorders. In that same year, Stanford professor David Rosenhan further exposed the arbitrary nature of psychiatric diagnosis when, under the title “On Being Sane in Insane Places,” he published the results of an experiment: he and seven others participants presented themselves at eight different hospitals, reporting that they heard a voice saying “thud,” or “empty,” or “hollow.” All were admitted, diagnosed with schizophrenia, and given antipsychotic drugs, even though they behaved normally once they were admitted. None of this was good for psychiatry’s public image.
In response to these challenges, the American Psychiatric Association convened a task force in 1974 to revise the DSM in a way that would redraw the lines of diagnostic categories. The goal was to create a uniformity of diagnosis: any patient should, on the basis of an interview, receive the same diagnosis from any doctor using the manual. One member of the task force expressed what many in the profession felt: “There is a terrible sense of shame among psychiatrists, always wanting to show that our diagnoses are as good as the scientific ones used in real medicine.” Psychiatrist Robert Spitzer, who led the task force and was himself frustrated with the indefinite results of the psychodynamic approach, proposed that DSM-III would be “a defense of the medical model as applied to psychiatric problems.” Committees assembled criteria sets for each category of illness, debated them, and agreed upon the number of symptoms within each set that would become the threshold for making a diagnosis.
As Spitzer recalled, the process of developing the new manual was anything but harmonious. Those committed to psychodynamic treatment felt marginalized, and were unhappy about Spitzer’s insistence that diagnoses of neurosis would not be included. Insurance companies would not pay to treat neurosis: “disorder” must be the preferred term. Going forward, biological dysfunction would be the presumed foundation of psychiatric illness, with the new diagnostic categories intended to catalyze research. A century on from Kraepelin, psychiatry was returning to its roots in science, demanding to be taken seriously once again as a field of medicine.
The newly created major depressive disorder provides an example of how difficult it was for the creators of DSM-III to set a sharp dividing line between mental health and illness. The threshold for the diagnosis required, for a period of at least two weeks, one of the disorder’s two core symptoms:
a depressed mood
a loss of interest or pleasure in one’s usual activities
And at least four of the following symptoms had to be present as well, for at least two weeks:
poor appetite or significant change in weight
insomnia or hypersomnia
psychomotor agitation or retardation
decreased sexual drive
fatigue or loss of energy
feelings of worthlessness, self-reproach, or excessive or inappropriate guilt
diminished ability to think or concentrate or indecisiveness
recurrent thoughts of death or suicidal ideation or suicide attempt
If you have one of the core symptoms and four of the others, you have the disorder. If you have one of the core symptoms but only three of the others, you don’t. The symptoms of melancholia—the illness that put Roland Kuhn’s patients in the hospital, the illness that responded unmistakably to imipramine and ECT—are here, and so are non-melancholic symptoms. Below the checklist are several specifiers, including “With melancholia,” with its own menu for a finer-grained diagnosis, and “With psychotic features.” But looking at the symptom menu for major depressive disorder one can’t help but ask: Do people with insomnia and hypersomnia have the same illness? Do these various symptoms, in various degrees, all derive from the same underlying physiological dysfunction? Perhaps. Or perhaps not. It didn’t matter how you had become depressed or why; what mattered was whether you met the necessary number of criteria, which could be determined (more or less) by a short interview.
As an effort to draw a clean line between disorder and non-disorder, the construct called “major depression” created yet another controversy. Psychiatrists using the new manual reported a newly “high prevalence” of major depressive episodes (MDEs) in their patient populations. A doctor at the VA Medical Center in the Bronx, for instance, noticed that “a large number of very mild depressives who would, appropriately, never be considered for a trial of medication or even psychotherapy, meet the criteria for MDE.” For authors Allan Horwitz and Jerome Wakefield, major depressive disorder was too inclusive, containing “all of the heterogeneous categories of endogenous, exogenous, neurotic, and even psychotic forms of depression that existed before 1980.” The DSM-III created the conditions in which people in all of these categories—as well as people with normal sadness who nonetheless met the criteria—could now be encouraged to take medication to ease their symptoms.
GIVEN THE CIRCUMSTANCES, the arrival of Prozac eight years later could not have been better timed. Had there been no DSM-III, no new and expansive definition of depression, it is hard to imagine any new drug commanding such a large share of the market. In another stroke of fortunate timing, in May of 1988 the National Institute of Mental Health launched Depression Awareness, Recognition, and Treatment (DART), an ambitious public/private program aimed at drawing attention to the dangers of untreated depression. Among the NIMH’s many partners in this project were pharmaceutical companies, who were invited to supply educational materials to health-care providers. Eli Lilly distributed eight million pamphlets about depression and the value of serotonin-enhancing medication to doctors’ offices just months after Prozac arrived on pharmacy shelves all over the country. While there is no doubt that initiatives like DART did help many people in whom depression went unrecognized, and that false positives are in the long run a far less serious problem than untreated depression, Lilly’s contribution to the DART public awareness program was a masterstroke of strategic marketing. To make prescribing as simple as possible for general practitioners, Lilly also brought out Prozac in one dosage only, the 20-milligram capsule.
An early ad in The American Journal of Psychiatry provided a schematic illustration to help potential prescribers visualize Prozac at work. It shows a balloon-like nerve ending filled with bright balls of serotonin, a neurotransmitter associated with positive mood. The text alongside describes what is special about the product: “Unique . . . Specific. Prozac (fluoxetine hydrochloride) is the first highly specific, highly potent blocker of serotonin uptake. Prozac. The most frequently prescribed antidepressant by psychiatrists in the United States.” In promoting the notion that their antidepressant could correct an imbalance in brain chemistry, Lilly also sold a new and readily understood explanation of depressive disorder and encouraged people to believe that depression is common, curable, and nobody’s fault. In doing so, they made it easier for people to ask for medication. If depression was a widespread dysfunction, there was no need to feel stigmatized. Social chatter about depression, long unmentionable by sufferers, was soon heard everywhere, and anyone who wasn’t on Prozac knew someone who was. What was so shrewd about this approach was that it quietly dodged those basic and inescapable questions of psychodynamic psychiatry: What experience lies behind these symptoms? And what is the meaning, or interpretation, of these symptoms? Who cares? Prozac helped. It had something to do with brain chemistry. Did anyone really need to know more than that?
Prozac’s selling point—the idea of making serotonin more available in the synapses—was made possible because psychoactive drugs like chlorpromazine and imipramine had become the basis of advancing neurobiological research. By the mid-1950s, scientists had identified neurotransmitters in brain tissue, and had also begun to understand the process of chemical signaling in the nervous system. Biochemist Julius Axelrod found that imipramine blocked the reuptake of norepinephrine at the site of the synapse between neurons, increasing its availability for transmission in brain circuits. Here was proof that imipramine interacted with a substance necessary for efficient signaling. When Joseph Schildkraut, a psychoanalytically trained psychiatrist, saw how imipramine improved the condition of his hospitalized patients, he was suddenly aware “that there was a new world out there, a world of psychiatry informed by pharmacology.” Convinced by the claims of Axelrod and others that depression was associated with an insufficiency of norepinephrine, Schildkraut published a paper in 1965 that was cited more often than any other in psychiatry’s journals—“The Catecholamine Hypothesis of Affective Disorders”—where he laid out the chemical imbalance theory of depression that would later be crucial in selling antidepressants to the public.
By the end of the 1960s, the Swedish pharmacologist Arvid Carlsson had discovered that some of the tricyclic antidepressants blocked the reuptake of serotonin, and an additional hypothesis, associating depression with an insufficiency of serotonin, was set in place. Working with antihistamines, Carlsson and his team discovered a serotonin-reuptake-inhibiting molecule called zimelidine, which promised to be as effective as imipramine and the other tricyclics. Taking their cue from Carlsson, in 1972 a team at Eli Lilly tested a large group of antihistamine-based compounds and found one that appeared to inhibit the reuptake of serotonin. This was LY-110140, later called fluoxetine hydrochloride, and later still, Prozac.
Carlsson’s antidepressant launched in Europe in 1981 and was about to be released in the United States when scattered reports of Guillain-Barré syndrome, a neurological disorder, caused it to be withdrawn. This left the American market open to Lilly’s entry, but it wasn’t until 1985 that fluoxetine showed evidence of antidepressant effects in randomized clinical trials. In all, it took sixteen years for LY-110140 to move from discovery through research, development, trials, and licensing to reach the market. Lilly hired Interbrand, the firm that branded giants like Nike, to give their drug a name that would send the right message. The team behind the launch said “We created the name Prozac, intentionally distancing it from everything typically associated with anti-depressants: strong chemicals, side effects and mood swings.” The two syllables, pro and zac, were meant to sound professional and energetic.
Prozac was a cultural touchstone of the 1990s right from the start. As the decade began, the now iconic green and ivory capsule appeared much enlarged on the cover of Newsweek with the headline, “The Promise of Prozac: A Breakthrough Drug for Depression.” The article proclaimed it “a wonder drug.” The New York Times described it as “one of the best antidepressants ever designed.” In his best-selling book Listening to Prozac, psychiatrist Peter Kramer speculated on the implications of a drug that could transform personality, making people less timid, more confident, more successful. Kramer was widely criticized for seeming to embrace a future in which people could choose to better themselves through what he called “cosmetic psychopharmacology.” But he wasn’t the only person speculating on such a future. Neuroscience promised to reveal a new understanding of mind and brain, as well as new solutions for the treatment of mental disorders. Journalists and scientists alike projected a near future in which pills would boost personality and performance. These would be created not so much for “patients,” a news article reported, as for “people who are already functioning on a high level . . . enriching their memory, enhancing intelligence, heightening concentration, and altering for the good people’s internal moods.” Released on the brink of what President George W. Bush designated the Decade of the Brain, Prozac dovetailed with this ambitious and optimistic outlook.
What is clear from the extraordinary early success of the second-generation Prozac-style antidepressants is not that they were uniquely effective medications, but rather that the power of their appeal consisted in the yearning for transformation invested in them by so many. People hoped, and were led to believe, that the SSRIs could aid them in becoming more assertive, more likeable, more cheerful, more the kind of person deemed successful in those years. That so many users failed to experience the transformation they wanted was only to be expected—these were chemical substances, not magical ones. Initial excitement was followed by widespread disenchantment, which was followed in turn by a normalization of expectations.
During its many years in development, the molecular formula (fluoxetine hydrochloride) that Lilly eventually marketed as Prozac didn’t impress anyone as a wonder drug. In 1981, a French neuroscientist noted that drugs like fluoxetine had not yet been released for clinical use “because of their not inconsiderable side effects.” These were effects on the central nervous system, like anxiety, insomnia, and nausea. Reactions of the digestive system result from the fact that 90 percent of the body’s serotonin is synthesized in the gut, where its function is to control digestion and to communicate hunger and satiety to the brain. The intestinal symptoms are unavoidable consequences of the drug’s global effect on serotonin, and they tend to subside as the body adjusts to the medication.
Today, these side effects and many more are listed as possible with the SSRI antidepressants, but they weren’t adequately acknowledged at the beginning. Mild to severe sexual dysfunction, including difficulty reaching orgasm, turned up in the majority of patients—as many as 70 percent rather than the 5 percent that Lilly listed at the outset. According to a 2014 issue of the Harvard Health Letter, “For many patients, SSRIs diminish sexual interest, desire, performance, satisfaction, or all four.” The big difference between Prozac and the tricyclics was that the so-called anticholinergic symptoms were gone: no dry mouth, no lethargy, greater physical energy.
While the tricyclic antidepressants affected several neurotransmitters, and the MAOIs inhibited the action of an enzyme that broke down neurotransmitters, Prozac targeted serotonin alone. This, Lilly argued, was what made it “clean,” or relatively free of side effects. When Prozac arrived, the earlier tricyclic and MAOI antidepressants were no longer under patent protection, and their makers had little incentive to advertise them. Compared to the tricyclics, Prozac was safer in overdose situations. The tricyclics required a physician’s oversight and the monitoring of the patient’s blood levels to determine the most effective dose. The MAOIs required careful attention to diet, because certain foods interacted with them to create life-threatening hypertension. Prozac seemed to present no such dangers or difficulties, and though it cost as much as twenty times more per capsule than these older, less exciting drugs, it seemed to be worth the price.
Other drug companies soon followed Lilly’s Prozac with similar offerings. The acronym SSRI, which refers to the entire class of drugs, was invented by SmithKlineBeecham for the launch of Paxil in 1993. Pfizer’s Zoloft came out in 1992, Forrest’s Celexa in 1998. The competition for customers raised the stakes. At first, Lilly advertised in the psychiatric journals, and then in general-interest magazines. The great advance for pharmaceutical companies came in 1997, when the FDA allowed drug makers to advertise directly to television audiences. With that, the triumph of drug advertising was complete: the industry’s directive—“Ask your doctor!”—penetrated the private home. By 2001, three of the ten best-selling drugs of any kind in the United States were SSRI antidepressants. That same year, Lilly’s patent on Prozac expired. In its thirteen years under patent protection, Prozac made twenty-one billion dollars in sales for Eli Lilly—roughly 30 percent of the company’s revenue during that period—and American doctors had written twenty-seven million prescriptions for it.
For Lilly and the other makers of SSRIs, the chemical imbalance theory was the key to success. In an increasingly competitive society, a drug that could top up an inadequate supply of a neurotransmitter, a lack that might be keeping you from becoming all you could be, was irresistible. Psychiatrist Jonathan Metzl writes of patients coming into his clinic saying, “I have a chemical imbalance that keeps me from getting married” and “I saw the Prozac ad in Self magazine and realized, ‘This is me.’ ” The theory was so widely embraced, and featured in so many ads for antidepressants, that in the public mind it took on the authority of fact. In Zoloft’s popular television commercials, molecules passing between “Nerve A” and “Nerve B” illustrated the chemical imbalance, while a sad, sighing blob suffers from depression or social anxiety. Many people found the animated creature adorable, and were able to ignore the long list of possible side effects in quiet voiceover as the blob emerged from his cave and became joyful. Forgotten was Schildkraut’s emphasis on the hypothetical nature of his paper, and his statement that his proposal was “at best a reductionistic oversimplification of a very complex biological state” involving brain metabolism and endocrine disturbances as well as other physiological and psychological factors.
In the absence of better explanations, psychiatrists might be forgiven for falling back on the simplicity of the chemical imbalance theory. Daniel Carlat describes his conversation with a depressed patient about an SSRI antidepressant introduced in 2002: “I explained that Lexapro worked by increasing the amount of serotonin in the brain, and it seemed to have fewer side effects than other anti-depressants.” But the process is not so easily understood, he writes, because “while Lexapro increases levels of serotonin in the nerve synapses, there is no direct evidence that depression is a disorder of reduced serotonin.” For Carlat, the chemical imbalance explanation was especially useful for patients who were reluctant to take medication: “Using these words makes their illness seem more biological, taking some of the stigma away from having a mental illness. The implicit message I deliver in using such language is ‘Your illness is biological, it is not your fault, and you are not going to be able to cure it by thinking it away.’ ”
“YOUR ILLNESS IS BIOLOGICAL, it is not your fault”: these are words that a depressive person longs to hear. Many patients would be told that depressives need antidepressants in the same way that diabetics need insulin. I heard this diabetes analogy for the first time from my own psychiatrist, when she suggested that I try Prozac. For several years I had been trying not to need antidepressants, taking them in bad times, stopping in better times, but resisting continuous use. It was getting to be obvious that I was inescapably a depressive person, as opposed to—well, in addition to—a person who was just going through a tough time in life. Separation and divorce, uncertainty about my career and my future employment, all of this kept me in a state of stress that increased my vulnerability to recurrent episodes.
Although it would become my medication too, I was unaware of Prozac’s existence when it first launched. Those were quieter days; there was no Internet, there were no television ads for antidepressants. By the end of 1987, when Lilly received approval from the Food and Drug Administration to sell Prozac for the treatment of depression, I had completed a part-time master’s degree in literature while working in book design, first freelance and then full-time for a publisher of glossy coffee-table books, putting in long hours for low pay. Then I quit the publishing world and worked for a friend who had a gardening business in Manhattan while I tried to figure out what to do next. I was in a state where decisions become impossible to make because everything feels wrong, because the self feels so damaged, helpless, and paralyzed.
As the days darkened and the anniversary of Anna’s birth and death approached, I began to have trouble sleeping. I wasn’t sure if I felt hopeless about the future because I needed to find more satisfying work, or because I was just a lost soul. I kept coming disconnected from my life, and could easily imagine myself homeless, jobless, and alone. I remembered the letter Paul had written me after I was discharged from the hospital, while he was still there and awaiting release. He said, “It’s funny, Mary; I still get sort of sad and feel alone and look off into space. Sometimes there seems to be no happiness left in me. I’m just hoping the lithium holds me up.” He was going to be placed in a supported living situation, which he said was “the best that could be arranged, I guess.” I had been assuming all this time that I was getting better, and that I was luckier than my friends in the hospital who were more disabled than I, and less able to have a normal life. And I was luckier. But I was finding myself again falling into the state Paul was describing, feeling existentially alone and afraid.
In an old folder, I found some passages that express my terror of the sick self that kept returning. I wrote them on a typewriter on a sunny January morning in 1988—coincidentally, just after Prozac was launched—as snow melted from the tips of hemlock branches outside the window and huddled in clumps on the neighbor’s roof. I was alone in the silent house, giving words to a waking nightmare.
I see a big house with no one in it, with paint peeling from all the shingles and a thick layer of dust covering the floors. The inhabitants have departed. In the last room at the end of the wide hall, there is a closet door slightly ajar. I walk across the room, my footsteps sounding impossibly loud in the stillness, and begin to feel apprehensive, even fearful, as I approach it and grasp the glass doorknob. A strange thrill enters my body, almost pleasurable until I recognize the feeling. It is terror. I pull the door open, quickly, before I can change my mind. Light floods the closet, which is under the eaves where the ceiling angles downward. I see—a woman. Her face is turned away. Her whole body is hunched, crouched on the floor. Her expression is first of surprise, then her eyes take on a look of recognition and cruelty. She makes no sound. We stare at each other. Then, like a wolf, she throws her head back and from her cloth-muffled body there emerges a howl that shatters the silence. The sound pierces my ears, pain fills my head and sends me staggering backwards, out of the room, out of the house, running. Because I know who that woman was. If my face were stripped of the nice and normal expressions that I use to fool people into thinking I’m like them, I would look just like her. I’ve been near there again, that place where time stops and I have to be shut away, because I can’t take care of myself anymore.
This fear—that something in me was making me unfit for love, for domestic life, for being a part of the human community—had to be suppressed as I tried to keep moving forward. I kept pushing it down, this fear that I might really be mentally ill. (Reading the passage above for the first time decades later, I recognized something I doubt I was conscious of as I wrote it: the woman’s crouched position is the position in which, in the shower at the hospital, I made that nearly lethal suicide attempt.) I didn’t usually think of myself that way, but each time this thing returned I was afraid that I might have to. And certainly my capacity for engaging fully in my life was stricken, and my confidence shaken, with each recurring episode. Each time the wave swept through, it washed away what little progress I’d made. Each time, I had to rebuild the little hut of myself, with ever smaller scraps and twigs of strength, willpower, and hope.
I recently asked Dr. Waters to share the list of drugs that she prescribed for me over the years. That January, just as Prozac went on the market, she again prescribed nortriptyline, the tricyclic antidepressant that I’d first taken while in the hospital. She didn’t mention Prozac at the time: given my quickly deteriorating condition, it would have made sense to work with a drug that she knew would help, rather than try something new and untested. That same month, I went back to graduate school, having been offered a fellowship to Columbia’s PhD program. On medication I soon felt hopeful again, excited by my work, able to breathe. During the summer, energized by my new freedom, I stopped taking medication once again. This was my life, so far as I can recall, while the Prozac revolution was quietly beginning.
I usually felt better during the summer, and when I felt better I tended to stop taking medication. I did this because being on nortriptyline was uncomfortable, and also because I had trouble coming to terms with the fact that I had a serious problem that kept returning. All that summer and fall I got by without medication, and by winter, not surprisingly, I was very depressed once again. Looking back on these years, it is clear to me—as it must be to any reader—that I wasn’t seeing the pattern. But if you’re feeling good, if you hate the side effects, if you want to get pregnant, you will want to stop taking meds. And until you hit a crisis, that seems to work okay.
In response to this decline—it was now the beginning of 1989—Dr. Waters suggested that I try Prozac. She recommended it enthusiastically, and I was more than happy to try it. Most doctors were impressed with Prozac’s relatively mild side effects, because side effects were what most often caused patients like me to stop taking their medication. In this regard, Prozac seemed like the breakthrough drug that psychiatrists and their depressive patients had been waiting for. I had high hopes that, if Prozac didn’t cause the heart palpitations and the dry mouth, the sluggishness and the heightened appetite that came with nortriptyline, I could stay on it.
Because I was immersed in graduate studies over the next few years, I wasn’t paying attention as the Prozac-taking population exploded. From conversations with my psychiatrist, I knew that Prozac was supposed to be a game-changer, but I wasn’t finding it so wonderful. At first, it seemed to be a great improvement. Its effect on my mood was similar to that of nortriptyline: I definitely felt better, although it was slower at delivering relief. There was no dry mouth, no racing heartbeat, and no weight gain, but orgasms could be elusive. It didn’t take long for people to begin to complain that their sexual lives were compromised on Prozac. While it’s true that during a major depressive episode one is far from feeling any desire, Prozac’s sexual side effects meant that many people, including me, stopped taking it as soon as they started to feel better. In and out of new relationships after my divorce, good sex was important, and sharing my mental health status with lovers wasn’t something I wanted to do.
Then I met someone whom, slowly and somewhat reluctantly, I came to love. Reluctantly, because I felt incapable of loving someone without also being ambivalent (if not downright negative, critical, and irritable—in other words, without acting like a depressed person) and without jeopardizing that person’s happiness as well as my own safety. I suspected that in any committed relationship I would again feel restless and claustrophobic. I was afraid of being alone forever, but I was equally afraid of risking marriage and its compromises.
When I was feeling low I was raw and sensitive and inhibited, and Jim’s outsized personality was hard to handle. He was in many ways my opposite: hyperenergetic, hyperproductive, hypertalkative. He was also generous, funny, and smart. He mirrored none of my own paralysis, self-deprecation, and despondence. I trusted in his essential goodness. Before long, I told him about Anna, my hospitalization, the whole grim tale. Eventually, we decided to marry and try to have a child. Because its effects on a fetus were still unknown, I stopped taking Prozac.
After our wedding we traveled through the southwest of England, then up to the Hebrides and the north of Scotland. We visited a friend in Italy and went hiking in Switzerland. So far, so happy. Then we settled down to work in a rented house in Cambridge, spending our days in the library and taking walks across the meadows in the evenings. Jim, an academic on a tenure track, was writing his second book; I was finishing my dissertation.
By the end of the summer I was irritable and negative, certain that I had made a terrible mistake in getting married. I would never be contented with anyone, I thought, and I would make anyone who loved me miserable. I kept these thoughts to myself, but I was panicking. It was crushing that the happiness and optimism of just a few months earlier had been so fleeting. The worries that anyone might have at the beginning of a marriage were amplified and distorted so much by the nihilism of depressive thinking that I really couldn’t tell what was true anymore.
We returned to New York at the end of the summer, and I checked in with my psychiatrist to let her know how I was doing. Because I couldn’t go back on Prozac while trying to get pregnant—or if I did become pregnant—we agreed to continue meeting weekly during this difficult period without medication. Toward the end of September, a legendary teacher of Columbia’s Literature Humanities course became terminally ill, and I was asked to take over his class. I wanted to say no, but I worried that if I didn’t say yes I might not be asked again. Had I known that I would be teaching that most daunting of courses, I would have spent a good part of the summer preparing. Imagine having only a few days to read and plan four hours of classes on Herodotus’s Histories and then, in a fragile psychological condition, walk into a seminar room to meet twenty or so first-year students who, having enrolled in a section with a star professor, could only be disappointed to see you. Imagine a week later having to teach Thucydides’s History of the Peloponnesian War, followed by the tragedies of Aeschylus, Sophocles, and Euripides, Virgil’s Aeneid, and other classics. Two students dropped the class immediately.
I tried to take that in stride. I needed to be engaging enough to win them over while also appearing authoritative and confident—a performance that, given my deepening depression, was difficult to pull off. One particularly tough morning, I realized I was shaking as I passed through the campus gates on my way to class. The shameful feeling that I was failing to teach well enough made me work all the harder. This stress only added to my other worries: I was thirty-six, trying to get pregnant, and had been without medication for months. I was also trying to make a life with Jim, while again doubting my ability to make a life with anyone.
As the weeks went by my anxiety rose to a near-unbearable level. I kept doing what needed to be done, and trying to meet my own high standards. I recently asked Jim what he remembered from that time, and he told me that for the first and only time in our years together, he feared that I might be suicidal. He was especially anxious when I was in the bathroom for what seemed like far too long a time, and once or twice, he said, he stood outside the door listening for signs of trouble. He was right to be worried. Down and down my mood was plummeting, so much so that one afternoon in November I opened the window of our fifteenth-floor apartment to have a look at the landing place below, a narrow airshaft between two buildings. I could see my body down there, smashed on the empty concrete alleyway between the sad ailanthus tree and the fence topped with razor wire. I wasn’t ready to do it, but I was checking out the possibilities.
It’s strange to say, but I had been so focused on pressing forward, resisting the despair, that only in that moment did I realize how much danger I was in. I called Dr. Waters immediately to tell her I needed to get back on Prozac. Because I had been trying to conceive, she said I should have a pregnancy test and based on the results, we would decide how to proceed. The pregnancy test, to my great surprise, was positive. Under the circumstances, this was unwelcome news.
Two weeks later, an ultrasound showed that I had again miscarried. The pregnancy, which the technician called a blighted ovum, had never been viable. I took a Prozac capsule as soon as I got home from the D&C. It took a little over two weeks, and then there was a loosening of the tightness in my chest, a quieting of the fear and the obsessive self-castigation, a greater sense of ease and possibility. When antidepressants begin to work, the relief feels almost like joy.
Earlier that year I had considered ending my psychotherapy, thinking I had learned enough to be able to go it alone. Therapy was expensive, and my insurance was limited. Now it was all too obvious that I shouldn’t do that. Dr. Waters suggested that we bolster the Prozac with lithium for a while until my mood began to stabilize. Despite years of work, I was unable to escape these periods of paralysis and hopelessness, and going without medication was clearly too risky. Dr. Waters suggested that what I couldn’t overcome was “hard-wired,” by which she seemed to mean that it was biological, and of such an archaic psychological formation—childhood habits of thought, childhood feelings—that it formed a bedrock layer of my character. She also suggested that I try to remember that this susceptibility to despair was a part of me—not the whole. I needed to keep that part as small as possible, even if I couldn’t eradicate it. The trouble was that once it was activated, as this last episode demonstrated, it was immensely powerful. Severe depression feels monolithic, but you can train yourself to remember that the mind thinking such terrible thoughts isn’t all of your mind, and doesn’t define you.
It took a long time to work all of this out, because it’s very hard to see yourself clearly when depressed. The problem is that you think with your mind, but your mind is ill and untrustworthy. Your mind is your enemy. Once you’ve lived through several terrible episodes, you begin to get a feeling for how the thing will go. (In a story he wrote while still in college, David Foster Wallace called it “The Bad Thing,” which nicely captures both the abstraction and the horror.) Eventually you realize that you can and do end up splitting yourself: a part of you can remain detached, watching the thing that is squeezing out any light and vitality within you. If a little space remains for the observing, rational consciousness, you can hold on. If not, you can get swept away in the delusion that you can never get better. Trying to kill yourself, for instance, is getting swept away. When the situation is critical, you need to have someone who knows how bad things are for you, someone to watch over you.
This person needs to be experienced and professional, and someone you completely trust, because he or she will hold the lifeline as the waves crash over you. This person should be your psychiatrist, not your spouse, your lover, your sister, or your best friend—none of whom should be exposed to the full force of your despair, or feel responsible for keeping you alive. Your psychiatrist is deeply invested, far more than you are yourself, in your survival, and knows that even a person in your wretched condition can survive. When I first tried to kill myself, I didn’t yet know this, and I didn’t yet have this kind of relationship with a psychiatrist. This is why the therapeutic bond between therapist and patient is such a crucial partnership. Severe, even suicidal depression can be managed. Surviving it teaches you that it is survivable. You take your meds. You keep in touch with your psychiatrist. You wait it out.
The moment when I opened the window and looked down led me, at last, to a reckoning. I was vulnerable, over and over, to this thing that just wouldn’t leave me. That feral madwoman in my brain kept trying to emerge. Nine years after my first suicidal episode, it was time to accept that this was what my life would be like. The severity fluctuated, but depression was always with me at some level. If I were going to try to get pregnant, it would have to be a pregnancy on medication.
Other decisions followed. Soon I would be finishing my dissertation and entering a ruthless job market where anyone lacking in confidence, anyone not having cultivated relationships with the right mentors, anyone without the ability to excite people about her ideas, was unlikely to be hired. I didn’t see how I could do well in an interview when just imagining an interview filled me with panic. Could someone with chronic low self-esteem and unpredictable but frequent depressive episodes succeed in the academic profession? It may be possible, but at the time I didn’t believe it would be possible for me.
Graduate school was competitive and stressful. During the three years of course work, I never got through all the pages assigned for my classes because I had a hard time concentrating. I realize now that it’s unlikely anyone got through them—maybe skimming and triage were all anyone could do to manage the reading load. Eventually I realized it was better to take a break than to sit at my desk reading the same sentence again and again, so I went running, or swimming. Exercise became a necessary daily stress reliever. Still, in seminars I looked around at my peers and felt like an outsider. I couldn’t find in myself their confidence or their obvious drive to succeed. Writing, so necessary for survival in a publication-driven profession, was for me extremely slow and dread-inducing. Somehow I won two writing prizes in graduate school, but a cruel internal critic continued to judge me a failure with every sentence.
In A Room of One’s Own, Virginia Woolf identifies the problem I was facing: “Life for both sexes . . . is arduous, difficult, a perpetual struggle. It calls for gigantic courage and strength. More than anything, perhaps, creatures of illusion that we are, it calls for confidence in oneself.” Is it true, as studies have suggested, that depressive people lack the self-inflating illusion that keeps so many people going? And that our less rosy outlook is just another name for realism? Perhaps—during our better times. But during a bad episode, the pessimism and self-disdain are delusional.
WATCHING JIM GO THROUGH a brutal tenure battle, I knew that I lacked the ego strength and the resilience to survive what he had just experienced. I needed to have a child, and I was running out of time. To try to heal the bitter trauma of the past was more necessary than having a tenure-track position. If I were going to try to get pregnant, I couldn’t extend my job search to a wide area and possibly end up living far away from my partner (as happens to many academic couples). After failing to get an interview for two positions at nearby colleges that year, I decided to take the more flexible path of staying in New York, teaching as an adjunct, and supplementing my low pay with freelance writing. Although in retrospect this choice of the less ambitious path sometimes looks cowardly to me, I know that at the time it was a pragmatic acknowledgment of my reality. Given that stress makes depression worse, this was a sensible, self-protective choice.
To step back and lower expectations for myself was to acknowledge that I was unsuited for a level of professional engagement that other people could manage. I had fought hard to return to “normal”; now I would simply stop hoping that “normal” was out there ahead of me. Life didn’t become much less stressful with this decision—Jim and I were both teaching full-time and we would, in the next few years, be undergoing infertility treatment as well. But at least I had laid down one part of my burden, the search for a tenure-track job.
I still didn’t fully accept an illness identity—I didn’t think of myself as “mentally ill” or disabled from day to day. I didn’t talk about my diagnosis or my troubles with anyone but the people closest to me. I went on trying to be like the other competent, professional adults I knew. But I made space for the depressive episodes that, it now seemed fairly certain, would continue to accompany me through life, and for the inevitable feelings of dejection, failure, and despondence. There was no making peace with this situation, but I tried not to enter into the feelings overmuch, and I tried to keep moving. My attitude shifted: instead of trying to outrun this fate, I would try to understand it.
From 1989 until 1992, I took Prozac for months at a time, and when I was feeling better I stopped for months at a time. Then, realizing I was suicidal once again, I took it faithfully, pretty much, for ten years. In 2002, while we were living for several months of a London winter in a mildewed garden-level flat near Hampstead Heath, I sank again into a state of blank inner deadness. Antidepressants, psychiatrists say, “put a floor under” patients who take them, and it’s an accurate metaphor. If a mood disorder is like a malfunctioning elevator, antidepressants stop the elevator at, let’s say, the basement level. This low and no lower, they command. Without meds, the elevator plunges ever lower, down to where suicide becomes a possibility. This time, Prozac was failing to put a floor under me. This common problem is usually addressed by increasing the dose, adding an additional medication, or switching medications.
When we returned to New York I switched to Lexapro (the brand name of escitalopram), a new SSRI just out that year. Gradually, I began to feel better than I had felt in many years. The sense of buoyant well-being was so unaccustomed that I began to wonder, “Is this how normal people feel?” The heavy wall of resistance that I’d had to push away in order to get anything done was simply gone. I began to feel pleasure in my days—more confidence and ambition, a greater ease and sociability and, as time went on, sustained relief from the oppression that had accompanied me for so long. Eventually Lexapro also stopped being quite so great, but on the whole it was better than anything I’d taken before. Because it had no noticeable side effects, it also allowed me to forget that I was on medication.
Like Prozac, Lexapro is an SSRI. So why, I wondered, did it provide greater relief than Prozac did? Escitalopram is a mirror molecule (an enantiomer) of citalopram, which had been on the market as Celexa since 1998. Patenting the mirror-molecule of an existing drug is one way that drug makers keep the money coming in when the earlier one goes off patent, since profits decrease drastically once a drug can be prescribed in generic form. But escitalopram—the “S” enantiomer of the citalopram molecule—is more potent and more specific in its effects on the serotonin transporter. Escitalopram, says its manufacturer, Lundbeck, is the “most selective” of the SSRI antidepressants.
If escitalopram is so effective because of its ability to bind to the serotonin transporter, then serotonin is clearly a piece of the puzzle of depressive illness, at least in my case. Scientists have long known that depleting serotonin in people who don’t have a depressive disorder does not make them depressed, but that serotonin is very low in the cerebral spinal fluid of people who have died by suicide. In the years since the chemical imbalance hypothesis was so widely adopted, more refined studies suggest that whatever the complicated causation of symptoms, increasing serotonin concentration contributes to repairing the brain’s neural networks. Serotonin is necessary for the body to make BDNF—brain-derived neurotrophic factor, which is in turn necessary to build neural connections. The loss of BDNF may be what accounts for the shrinkage of the hippocampus in the brains of people with severe depression. It is possible that I noticed such an improvement on Lexapro because my brain was functioning better than it had been in a long time.
So I lived my life, taking Lexapro every day and doing pretty well, until a growing controversy became impossible to ignore: Were the SSRIs truly effective over the long term? Was it possible that they were doing more harm than good? By 2010 or so, anyone taking an SSRI regularly and following coverage of the debate was pitched into a state of uncertainty. The book that caught everyone’s attention was The Emperor’s New Drugs by the psychologist Irving Kirsch, who had been researching placebo effects for years. It was based on a study he’d coauthored and published in 2008 in the journal PLoS Medicine, in which his team reviewed the trial data of the six most widely prescribed SSRIs. These were all of the double-blind, placebo-controlled trials completed before those drugs were approved by the FDA, and included unpublished trials with negative results. Kirsch and his colleagues concluded that these antidepressants were barely more effective than placebo for the majority of people who take them, and they are most effective for patients “at the upper end of the very severely depressed category.” Eli Lilly pushed back, declaring that Lilly was proud “of the difference Prozac had made to millions of people living with depression.” A rash of news reports and publications followed, questioning the ethics of drug marketing as well as the fact that so many psychiatrists had been willingly seduced by drug reps who offered free lunches, paid junkets, even actual payments, in return for talking up the benefits of a particular drug at a conference or prescribing it readily to patients.
Then, in the summer of 2011, Marcia Angell’s article, “The Epidemic of Mental Illness: Why?,” appeared in The New York Review of Books. She discussed Kirsch’s book along with two others that criticize the overdiagnosing, overmedicating, and overselling of mental illness—Daniel Carlat’s Unhinged: The Trouble with Psychiatry and Robert Whitaker’s Anatomy of an Epidemic. This article and the one that followed it in a two-part series, “The Illusions of Psychiatry,” caused a great deal of consternation: accusations of bias and defenses of psychiatric practice appeared in the many impassioned letters of response.
While many details of Angell’s article were troubling—including the increasing prescription of antipsychotic medications for children as young as two—the most unsettling as it related to my own situation was Whitaker’s assertion that psychoactive drugs create dependency by altering the brain’s neurochemistry. If a person stops taking the drug, the brain is no longer used to performing without it. Relapse awaits, with the inevitable return to the medication. This was a possibility I had never heard about. Whitaker is an award-winning investigative reporter and author of a book called Mad in America, which is also the name of the website he runs. He is considered an antipsychiatry fringe figure by many in the profession, but his argument about dependency and relapse was based on reputable sources. One part of it comes from a 1996 paper by the neuroscientist Steven Hyman, a former director of the National Institute of Mental Health and now the head of the Stanley Center for Psychiatric Research at Harvard and MIT’s Broad Institute. The long-term use of psychiatric drugs, Hyman wrote, results in “substantial and long-lasting alterations in neural function,” so that the brain begins to function in a manner “qualitatively as well as quantitatively different from the normal state.”
The Italian psychiatrist Giovanni Fava had published a paper in 1994, also cited by Whitaker, arguing that psychiatric drugs “perturb” the pathways in the brain of the neurotransmitters they target. The brain adapts to this perturbation by trying to restore “homeostatic equilibrium.” In the case of the SSRIs, which produce an extra supply of serotonin, the brain may shut down some portion of its own production of serotonin or its serotonin transport mechanism. “Oppositional tolerance” is Fava’s term for this process. This may explain why, for so many people, antidepressants are less and less effective over time.
My reading of Angell’s articles, and my subsequent reading of many other writers on the controversies she raised, left me with so much confusion and unease that I decided to begin my own investigation. Amid the lack of scientific clarity about the functioning of neural networks in mental illnesses, the muddle of diagnostic criteria, the uncertainty about what exactly psychiatric medications are doing to the brain, and debate about their long-term effects, where is the truth? What is the state of my brain, and is it worse than it would have been had I not taken antidepressants continually for the past twenty-five years? My investigation has involved looking closely at my past, and has brought me to this conclusion: I am someone who should not stop taking medication.
I SWITCHED MEDICATIONS AGAIN when after thirteen years on Lexapro I believed that it was no longer doing much for me. I began taking Wellbutrin, a non-SSRI that affects the norepinephrine and dopamine systems. As with the tricyclics, I had trouble with an elevated heart rate, as well as lots of discomfort caused by dry sinuses. I had to reduce the dose to the point where it didn’t have much effect, and then I gave up and began taking a recently developed SSRI-style drug called vortioxetine.
Daily use of these medications has meant that I haven’t had a dangerous episode for many years. It’s clear that the maintenance approach—taking medication every day—prevents those deep depressions from happening as frequently as they used to. Still, I would love to stop taking medication and get by with lots of exercise, a healthy diet, and the support of my family and friends. I would then be my full and “true” self, open to a whole range of emotion. So the fantasy goes. But it’s just not worth the risk. Evidence from numerous studies shows very clearly what I’ve recounted from my own experience. For people like me, depressive illness is progressive and unrelenting: only the steady use of medication protects against it. Readers who take antidepressants will recognize this trial-and-error process of trying to live without medication, as well as its less than ideal results. Whatever their drawbacks, the drugs have provided what’s called “neuroprotection” against the physiological processes underlying my depression.
The antidote to outraged polemics against medicalized psychiatry like Angell’s and Whitaker’s, I’ve found, is in the calmer voices of clinicians who write about seeing patients day after day, and know through this ongoing work that despite arguments to the contrary, antidepressants certainly do help people. Richard Friedman, a clinical psychiatrist and a frequent contributor to The New York Times, offered his skeptical and pragmatic point of view: “The hypothetical risk of long-term SSRI treatment is dwarfed by the very real risk of untreated depression, which carries a 2 to 12 percent risk of suicide.”
Psychiatrist Peter Kramer, the author of Listening to Prozac and Against Depression, wrote a New York Times editorial arguing that Kirsch’s study was weakened both by his choice of data and his statistical analysis of that data. Like Friedman, Kramer believes that despite undoubted overprescription, too many people with severe depression still go untreated. Kramer recently weighed in on the “antidepressants don’t work” controversy with a full-length book called Ordinarily Well, an exhaustive and persuasive refutation of Kirsch’s conclusion that antidepressants are merely expensive placebos. He writes, “I have seen antidepressants pull patients from the brink and hold them steady.”
Since I’m one of the people for whom antidepressants clearly do something, I gratefully attest to their positive effect. They’re not perfect by any means, but I’m lucky that they work for me. They have the power that Kramer claims they do, to pull me back from the brink, and hold me steady. And yet, after a period of time, the incredible sense of relief and well-being that they produce when I begin taking them in the midst of a grim episode—this fades, and feeling flattens out. Enthusiasm and true pleasure are more difficult to access. The “holding steady” becomes a steady, detached, and flattened state. I have heard and read that many people on SSRIs complain about this flattening of emotion, which is ironic because it’s just what depression produces. I first recognized it at the age of sixteen or so: the inability to feel.
The default on meds is neither high nor low, and “feeling” feels more like thought. I don’t know whether this lack of feeling (or excitement, or enthusiasm) could be defined as anhedonia, but it is something like that. Maybe this is the problem with the new neural baseline that the meds have created: you won’t go lower, but neither will you go higher. When I’m tempted to stop taking my medication, it’s because I want to feel all that I’m capable of feeling. Not the very low lows, but the emotions of a person who is fully alive to the moments and days of her life, and not at a slight remove. Surely, between episodes, there should be a return to a full emotional range? If so, that is what I don’t experience on continuous medication. Is the flattening a medication effect, or a lingering aspect of the illness that medication leaves untouched? Or both?
I have enormous respect for Peter Kramer, Richard Friedman, and other clinicians like my own psychiatrist who continue to work intensively with patients using a combination of talk therapy and medication. But unless psychiatrists themselves have lived for decades on antidepressants, they can’t know how it feels to be hostage to medications whose long-term effects upon the brain and body—how responsiveness might be dulled, how neural networks might be altered, what effects are transmitted to a child during pregnancy or in breast milk—are still not entirely clear. This is a situation that didn’t exist before the 1950s, when the first psychoactive drugs came into being. While it appears that they are safe in long-term use, there has been no systematic study of SSRI effects that lasted longer than ten years. We who take these medications regularly, whether we like it or not, remain the subjects of an experiment whose outcome may not be known in our lifetime.
The so-called “pipeline” for new antidepressants is nearly empty now, and most pharmaceutical companies have transferred energies and investment away from trying to produce new remedies. There’s little profit in it. They have no new paradigms for treating depression; all of the drugs since imipramine and Prozac have been variations on a type: they modify neurotransmitters. They are a blunt instrument, modifying neural pathways in ways not understood, creating change but not cure. While we await a more thorough understanding of the processes that result in severe depression, and until the next treatment innovations arrive, these drugs—imperfect, uncomfortable, but life-saving nonetheless—are what we have.