Contents
Cover
About the Book
About the Author
Also by Andrew Solomon
Dedication
Title Page
Epigraph
A Note on Method
I: Depression
II: Breakdowns
III: Treatments
IV: Alternatives
V: Populations
VI: Addiction
VII: Suicide
VIII: History
IX: Poverty
X: Politics
XI: Evolution
XII: Hope
Epilogue
Notes
Index
Acknowledgments
Bibliography
Copyright
Andrew Solomon is the author of one novel, A Stone Boat, published in 1994, and a previous work of non-fiction, The Irony Tower: Soviet Artists in a Time of Glasnost, published in 1991. He writes regularly for the NewYorker and the New York Times Magazine. A dual US/UK national, he was educated at Yale and Cambridge and now lives in New York and London.
ALSO BY ANDREW SOLOMON
A Stone Boat
The Iron Tower: Soviet Artists in a Time of Glasnost
For my father,
who gave me life not once, but twice
THE WRITING OF this book has been my life for the past five years, and it is sometimes hard for me to trace my own ideas back to their various sources. I have attempted to credit all influences in the notes at the back of the book, and not to distract readers with a cascade of unfamiliar names and technical jargon in the main text. I asked my subjects to allow me to use their actual names, because real names lend authority to real stories. In a book one of the aims of which is to remove the burden of stigma from mental illness, it is important not to play to that stigma by hiding the identities of depressed people. I have, however, included the stories of seven people who wished to remain pseudonymous and who persuaded me that they had significant reason to do so. They appear in this text as Sheila Hernandez, Frank Rusakoff, Bill Stein, Danquille Stetson, Lolly Washington, Claudia Weaver, and Fred Wilson. None of them is a composite personality, and I have taken pains to change no details. The members of Mood Disorders Support Groups (MDSG) use first names only; these have all been changed in keeping with the private nature of the meetings. All other names are actual.
I have allowed the men and women whose battles are the primary subject of this book to tell their own stories. I have done my best to get coherent stories from them, but I have not in general done fact-checking on their accounts of themselves. I have not insisted that all personal narrative be strictly linear.
I have often been asked how I found my subjects. A number of professionals, as noted in the acknowledgments, helped me to gain access to their patients. I met an enormous number of people in my ordinary life who volunteered, upon learning of my subject, their own copious histories, some of which were extremely fascinating and ultimately became source material. I published an article about depression in The New Yorker in 1998 and received over a thousand letters in the months immediately following publication. Graham Greene once said, “I sometimes wonder how all those who do not write, compose, or paint can manage to escape the madness, the melancholia, the panic fear which is inherent in the human situation.” I think he vastly underestimated the number of people who do write in one way or another to alleviate melancholia and panic fear. In responding to my flood of mail, I asked some people whose correspondence had been particularly moving to me whether they would be interested in doing interviews for this book. Additionally, I spoke at and attended numerous conferences where I met consumers of mental health care.
I have never written on any subject about which so many people have so much to say, nor on any subject about which so many people have chosen to say so much to me. It is frighteningly easy to accumulate material about depression. I felt in the end that what was missing in the field of depression studies was synthesis. Science, philosophy, law, psychology, literature, art, history, and many other disciplines have independently taken up the cause of depression. So many interesting things are happening to so many interesting people and so many interesting things are being said and being published—and there is chaos in the kingdom. The first goal of this book is empathy; the second, which has been for me much more difficult to achieve, is order: an order based as closely as possible on empiricism, rather than on sweeping generalizations extracted from haphazard anecdotes.
I must emphasize that I am not a doctor or a psychologist or even a philosopher. This is an extremely personal book and should not be taken as anything more than that. Though I have offered explanations and interpretations of complex ideas, this book is not intended to substitute for appropriate treatment.
For the sake of readability, I have not used ellipsis marks or brackets in quotations, from spoken or written sources, where I felt that the omitted or added words did not substantially change meaning; anyone wishing to reference these sources should go back to the originals, which are all catalogued at the end of this book. I have also avoided use of “[sic]” in the eighth chapter, where historical sources use obsolete spellings. Quotations for which citations are not furnished are from personal interviews, most of which were conducted between 1995 and 2001.
I have used those statistics that come out of sound studies and have been most comfortable with statistics that have been extensively replicated or frequently cited. My finding, in general, is that statistics in this field are inconsistent and that many authors select statistics to make an attractive ensemble in support of preexisting theories. I found one major study, for example, that showed that depressed people who abuse substances nearly always choose stimulants; and another, equally convincing one that demonstrated that depressed people who abuse substances invariably use opiates. Many authors derive a rather nauseous air of invincibility from statistics, as though showing that something occurs 82.37 percent of the time is more palpable and true than showing that something occurs about three out of four times. It is my experience that the hard numbers are the ones that lie. The matters that they describe cannot be defined so clearly. The most accurate statement that can be made on the frequency of depression is that it occurs often and, directly or indirectly, affects the lives of everyone.
It is hard for me to write without bias about the pharmaceutical companies because my father has worked in the pharmaceutical field for most of my adult life. As a consequence of this I have met many people in that industry. It is fashionable at the moment to excoriate the pharmaceutical industry as one that takes advantage of the sick. My experience has been that the people in the industry are both capitalists and idealists—people keen on profit but also optimistic that their work may benefit the world, that they may enable important discoveries that will put specific illnesses into obsolescence. We would not have the selective serotonin reuptake inhibitors (SSRIs), antidepressants that have saved so many lives, without the companies that sponsored the research. I have done my best to write clearly about the industry insofar as this is part of the story of this book. After his experience of my depression, my father extended the reach of his company into the field of antidepressants. His company, Forest Laboratories, is now the U.S. distributor of Celexa. To avoid any explicit conflict of interest, I have not mentioned the product except where its omission would be ostentatious or misleading.
I was frequently asked, as I wrote this book, whether the writing was cathartic. It was not. My experience conforms to that of others who have written in this field. Writing on depression is painful, sad, lonely, and stressful. Nonetheless, the idea that I was doing something that might be useful to others was uplifting; and my increased knowledge has been useful to me. I hope it will be clear that the primary pleasure of this book is a literary pleasure of communication rather than the therapeutic release of self-expression.
I began by writing about my depression; then about the similar depression of others; then about the different depression of others; and finally about depression in completely other contexts. I have included three stories from outside the first world in this book. The narratives of my encounters with people in Cambodia, Senegal, and Greenland are provided in an attempt to counterbalance some of the culturally specific ideas of depression that have circumscribed many studies in the area. My trips into unknown places were adventures tinged with a certain exoticism, and I have not suppressed the fairy-tale quality of those encounters.
Depression, under various names and in various guises, is and has always been ubiquitous for biochemical and social reasons. This book strives to capture the extent of depression’s temporal and geographical reach. If it sometimes seems that depression is the private affliction of the modern Western middle classes, that is because it is in this community that we are suddenly acquiring new sophistication to recognize depression, to name it, to treat it, and to accept it—and not because we have any special rights to the complaint itself. No book can span the reach of human suffering, but I hope that by indicating that reach, I will help to liberate some men and women who suffer from depression. We can never eliminate all unhappiness, and alleviating depression does not assure happiness, but I hope the knowledge contained in this book will help to eliminate some pain for some people.
Since
for T.R.K.
TWENTY YEARS HAVE passed since my first serious depression. I’ve had a mental illness for nearly half my life, and I can no longer imagine myself without it. It seems less like something that happened to me than like part of who I am; some days, it is the thing about me, but it is always at least a thing about me. I no longer contemplate a time when I’ll be out of treatment, any more than I imagine a time when I will give up eating or sleeping. It’s a challenge to sort out how much depression defines me because of my experience with the illness itself, and how much it is engraved in my identity because of the public stance I’ve taken by talking about it. Writing The Noonday Demon turned me into a professional depressive, which is a weird thing to be. A class at the university I attended assigns the book and invited me to be a guest lecturer. As an undergraduate, I had dreamed of being a writer so accomplished that students there would study my work. But when I hatched that fantasy, I didn’t envision the work as a memoir assigned in an Abnormal Psych course.
Any consideration of depression has become a matter of dialectics. On the one hand, my life is so much less affected by the condition than it once was that sometimes the darkness of those original episodes seems like a distant dream. On the other hand, feeling secure is almost always the prelude to one of my occasional relapses, and when depression hits, I feel all over again that I will never escape the darkness. On the one hand, I’m more accustomed to such plunges than I used to be; I can feel depression hatching just as arthritics can feel imminent rain. On the other hand, it’s shocking every time; I forget how physical it is, how relentless it feels: the tightness in my chest, the sluggishness. I forget the crushing of my ego, the struggle not to believe that every distorted thought is an insight. When I’m not depressed, I draw strength and beauty from depression; when I am depressed, I find no such things. I cover for it better than I used to; I can function surprisingly well even when I feel as if I’m dying—or as if I’d like to die. But anxiety remains my worst enemy, and I periodically wake up feeling that the day is more than I can possibly handle. A regimen of therapy and medication seems a small price to pay for relative equanimity, but I hate the time and management it all requires. I loathe having a fragile brain and knowing as I make any plan that I should provide for the possibility that my mind may betray me at short notice. I haven’t left depression behind; I only hold it at bay.
I have had great fortune over these past twenty years. I’ve met and married my husband, John, the kindest person I’ve ever known, and I’ve had children who both demand and provide great happiness. Certain aspects of steadiness we can create for ourselves, but stability also comes from other people, and John has ballasted me. He is patient and gentle when I’m down. I am no longer alone in depression, and that is a pivotal change. I can have the subjective feeling that life is intolerable, but I usually know intellectually that what I feel is inconsistent with what is true: I have a nice life. I’ve found a brilliant psychopharmacologist who has fashioned a medication regimen that is effective most of the time, with relatively minor side effects. We’ve worked out just how to tinker when trouble looms. For talk therapy, I see a psychoanalyst who is both wise and funny. When I was once rather cavalier about some early warning signs of depression, he remarked, “In this room, Andrew, we never forget that you are entirely capable of taking the express elevator to the bargain basement of mental health.”
I regulate my life. I never miss a single day of my medication. With the input of my two doctors, I adjust dosages and attempt to modify my behaviour as soon as I recognize the slightest hint of a relapse. Propranolol, a beta blocker that I can use when I feel especially anxious, slows down my heart and lets me breathe. It doesn’t have the sedating effects of the benzodiazepines. In 2012, I increased my dose of Zyprexa, the drug that has helped mute my clinical anxiety for the last fifteen years, then brought it partway down a few months later. It took me nearly two years to go the rest of the way back down; it was so difficult to find the right moment to face the possibility of escalating disquiet. I am fanatical about sleep and am willing to put off almost anything to make sure I have enough of it; John is the one who gets up with our children in the night if getting up is required. I exercise regularly, as much for my mental as for my physical well-being. I consume little alcohol and even less caffeine (although I have a weakness for chocolate, which, sadly, I can’t eat if I’m feeling anxious).
At the same time, there are some concessions I’m unwilling to make. I lead a stressful, fascinating life, and I’m not going to curtail it. I go everywhere and am devoted to too many people; I have a crush on my own ideas and a thirst for other people’s ideas; I am a klutzy but enthusiastic juggler of family, friends and work. I’d rather take my meds and inhabit the world than reduce them and close it off. When I’m well, I do everything I can, and sometimes that looks like bipolar II. But my behaviour is not hypomanic; rather, it reflects my understanding that the ability to operate could forsake me at any time, and that I should exploit my functional periods for all I can.
My children are sometime antidepressants for me. I promised myself never to consider suicide once I became a parent, and not to act depressed around them if I could avoid doing so, and being with them strengthens those benign obligations. The sound of their voices has a miraculous effect when I’m mildly to moderately depressed. Although they can, of course, make me furious and worried, they never make me feel less enmeshed in the world. Yet I try to protect them not only from my depression but also from their ability to mitigate it, because I don’t want them to take that on as an obligation. John is a huge help whenever I’m low; being in our room together feels safer than being in my room alone ever did, and I don’t insulate him from my reality very much. Love helps when the depression is in its earlier stages. But when it really escalates, much of that power evanesces. I can tell that things are growing dire when my anxiety is deaf to my children’s laughter. At that point, my job is to protect the children from my disengagement, to act out the way I wish I felt. That has to be the most exhausting enterprise in the world, though there is a certain grim satisfaction in carrying it off.
My life in the twenty-first century has been marked by periodic relapses. In 2002, I tried going off Zoloft for a while to escape the sexual side effects. I suddenly found myself with boundless sexual energy—with ridiculous amounts of it, and with delusions about my own charms. It spiced up my relationship with John; at the same time, I felt as though there were sexual implications in my interactions with the mailman, with the grocery-store clerk. There was a sexual edge to my interactions with the dog walker; there was a sexual edge to my interactions with the dog. Quite soon after those developments, I began drowning in that flow of despair that I’d held off for so long. It took me about six weeks to realize that I was becoming completely crazy. I went back on my Zoloft, and things calmed down.
At Christmas 2003, John moved from Minneapolis to New York to live with me. I had been after him to do so for a long while, but his actual arrival stirred up various anxieties. The last person who had moved in with me had ended up vanishing out of my life in a particularly distressing way, and the anxiety triggered by John’s presence at home was more than I could handle. I had made the misguided decision about a month earlier to go off Zyprexa because it was making me fat and sluggish. I was now both chemically and emotionally destabilized. Getting what you’ve asked for and then moping seems churlish, and I was worried it would destroy the relationship. I had to figure out how to construe my bleak mood as being about something else. That depression hit full force; I was nearly unable to talk. I had seen an endearing but dopey musical a month earlier, and now I listened to the recording of it over and over and over and over, as though the adorable rhythms of its pointlessly upbeat songs were my lifeline to happiness.
Right after Christmas, I was supposed to fly to Antarctica in a military plane on a journalistic assignment and report for three days. I had always, always, always wanted to go to Antarctica, and I had bought all the necessary clothing and provisions. It soon became clear to me, however, that I would not be making the trip, and that my nonrefundable costs were for naught—a folly that drove me nearly insane with dismay. Now that I am well, I can’t see what was so difficult. I merely had to throw some clothes in a suitcase and sit on a plane for a while, then see some beautiful sights with cordial experts with a view to describing the experience later on. Less than two years earlier, I had gamely travelled to Afghanistan during the war there to report for the New York Times. Now, I felt as if I were suffocating; I couldn’t seem to catch my breath. I disappointed my editors; I also disappointed myself, as I had thought I was past this kind of apparent nonsense. When I am feeling well, I think that depression is just caving in to indolence, a matter of not bothering with difficult things. Then the depression hits and wham—I can’t do it. I could no more have flown to Antarctica on a military plane that winter than I could have swum there from New York. So I went back on Zyprexa. John and I adjusted to our new intimacy. Bit by bit I crawled back up into the oxygen of my own life.
My most recent major episode came when I published Far from the Tree: Parents, Children, and the Search for Identity, in late 2012. I felt that relentless nakedness dawning again: I had put more than a decade into writing the book, and the possibility that it would fail consumed me. My original depression had struck when I published my novel A Stone Boat in 1994, and that concurrency has inflected all of my subsequent publication experiences. Now, I was afraid that no one would notice my new book. I was worried that people I’d interviewed might find fault with my portraits. I was concerned that I’d overlooked some terrible flaw or gap in what I’d written. Mostly, though, I wasn’t worried about anything I could name; I was just worried. All the time. I felt as if I had been plugged into an electric socket from which I could not disconnect myself. People kept telling me how excited I must be, and I did my best to play along. I declared myself excited. I acted excited. I went on TV and on the radio and spoke excitedly. But all the while, I felt as though the world were coming to an end; I felt as though the people I loved were going to meet tragic demises; I felt as though I were going to forget how to swallow or breathe. I felt that if I backed out on the least significant commitment, I’d plummet and die; I felt as though if I kept going at my breakneck pace, I’d explode and die.
I gave my first lectures about the book and knew they weren’t good enough, that my ideas were a big muddle. I felt suddenly old and hopeless. My stress level shot up, and I began to experience that familiar panic that I couldn’t make it through the day. When I was sleepless at night, I thought that exhaustion would surely undermine my functioning, but when I finally started to drift off, I feared that I would oversleep and miss my morning commitments. I would wake up in a hotel room incapable of folding my clothes to put them back in my suitcase. I was always terrified that my luggage would be lost, or that I’d forget where I was expected next.
Yet publishing the book was also thrilling. When I didn’t feel like crying, I was cheerfully congratulating myself. It was a bizarre mixed episode; I felt overjoyed and terrible all the time. The only thing that seemed to break the fever pitch was my children; with them, I felt sane and happy. But as soon as they left the room—or as soon as I did, which happened more often, given all I was trying to do—the effect was broken, my despair compounded by guilt for leaving them.
One of the problems with mental illness is that it leaves you permanently unsure what’s “real” and what’s “just in your head”. On the first day of my book tour, I developed what felt like an ear infection. I wondered whether I should be flying, but book tours involve flying, and we’d all worked diligently to set this one up. So I kept boarding planes while wondering what to do about my ear. I couldn’t hear the questions from people in my audiences. My doctor, reached by phone, suggested heavy doses of Afrin, an over-the-counter nasal spray. My balance was off, presumably because of aural congestion, and I felt unsteady on my feet. I nearly missed one flight because I failed to hear the repeated announcements of a change in the departure gate. I developed tinnitus, a ringing in my left ear that sounded like perpetual screeching brakes.
Finally, during the Miami Book Fair, I ended up at an urgent-care clinic full of screaming children, where a young doctor reassured me that my ears looked fine, but that I could have some antibiotic drops. I began to surmise that my symptoms, which distracted me from obsessing about my reviews, might be hysterical; I wondered whether my hearing loss could be either the source or the product of my depression. That night, friends invited me for dinner at their apartment on the beach, and one of them, a psychiatrist, wrote me a prescription for stronger antibiotics, which I took for a week.
I made an appointment to see an otolaryngologist when I returned to New York for Thanksgiving, and upon examining me, he announced, “You have sensorineural hearing loss.” He explained that I appeared to have lost much of the hearing in one of my ears, probably permanently. He prescribed steroids and instructed me to come back for another test in a few weeks. He advised that the chance of my losing my hearing in the other ear was about the same as the chance of losing my hearing in this one had been before and suggested that I had possibly contracted a virus that had damaged the hair cells of my inner ear. He added that I should also be checked for tumours on my auditory nerve.
At Thanksgiving, I couldn’t hear what was going on at a crowded holiday table. I felt utterly alone, even among my family and friends. I decided to cancel the rest of my book tour; I started to cancel it; I decided not to cancel it. My editor knew a doctor in Seattle who could examine my ear when I arrived at the end of the holiday weekend. I landed in Seattle, recorded some radio interviews, and went to a neurological institute, where I was prescribed a series of injections of steroids directly into my eardrum. Thus I began a new routine: arriving in a new city, visiting a new hospital, redoing all the paperwork, getting needles thrust into my ear, and then shuttling off to do media appearances and lectures. I kept asking myself whether I had really lost my hearing; I kept imagining that I had somehow done this to myself with my own depression, as though the depression were something I had done to myself. I was fast discovering why people have stereoscopic hearing. My sense of balance was now completely gone and I fell several times. I couldn’t hear out of my left ear, and it felt as though I had a tennis ball stuck in my ear canal—though the doctors had assured me that no obstruction was there.
I have some permanent hearing loss in my left ear, and apparently permanent tinnitus, and those are physical symptoms, and extremely irksome. It’s nowhere near as bad as it was at first, either because some of my hearing came back organically or because my anxiety about it abated. I can manage the announcements in airports. I sometimes have trouble in noisy restaurants, but I think I’ve had that trouble for years. I wore a hearing aid for a few months, then realized I could manage without it—because my auditory hair cells healed, because some secondary inflammation resolved, or because the dark mood passed. I was okay again. I no longer inexplicably fell. Something physical had definitely gone wrong, and something psychological as well, and I still have no idea if and how they were connected.
So that’s one of depression’s legacies: I no longer know how my mental and physical health are playing off each other. I’d love to have a Cartesian certainty about mind and body, but I don’t. I never have a stomach ache without wondering whether what has disrupted my digestion is food poisoning or irrational fear. When I can’t sleep, I wonder whether my mind is racing as everyone else’s mind races sometimes, or whether I might be reaching a pitch of clinical anxiety. I’d like to know for sure when I am actually facing hostility and when I’m being unduly paranoid. Wary of caving in to depression, I almost never admit to defeat by anything except math, folk dancing and team sports. I try feats such as hang-gliding and travel to war zones because I am so bloody-minded about not missing out on anything as a result of depression. When I compromise a friendship, I always try to repair it; I assign the damage to my psychiatric state rather than to the wear and tear that life inevitably imposes. My nostalgia takes the form of trying to mend the past. I have the neurosis of depression and I am neurotic about my depression.
People ask me if it hasn’t been terribly burdensome to talk so openly about my psychiatric challenges. They suppose that I am mocked because of them. I am happy to say that if I am, it’s mostly behind my back, though I do catch the occasional flash of jeering on Twitter. The most startling revelation from being a professional depressive has been how commonplace depression is. When I tell people that I have suffered from depression, the almost universal response is “I’ve been so worried about my sister” or “My best friend killed himself last year and I feel so guilty about not understanding it” or “I’ve been depressed for years”. I rarely meet anyone who doesn’t launch into a confidence. It has sometimes felt as though my book were one of those full-body scanners at the airports that allow personnel to see what people are hiding under their clothing. Perfectly self-possessed individuals, many of them strangers, reveal the numbness or agony they or their closest relatives confront every day. People I’ve never met sometimes hug me in public places because this book’s stories about depression have made them feel less alone. I am honoured by the trust and enthusiasm, though it can be tough when my own mood is fragile to take on someone else’s.
I receive a steady stream of correspondence from depressed people seeking my advice. I don’t necessarily have sagacity beyond what’s in these pages, but the letters are both wonderful and awful: wonderful when they indicate that anything I’ve written or said has helped, wonderful because of the community they establish; awful because they reveal to me daily the pain of life, the anguish of people who have not received or have not responded to treatment, or who are simply lost in a dark wood in the middle of their lives. Some days, I feel like the guru dispensing wisdom; some days, I feel like the depressive who can’t help even himself. My favourite letter came from someone who wrote without giving a return address: “I was going to kill myself, but I read your book and changed my mind.” When I am feeling low, I sometimes chant that line to myself. I have learned that I’ve felt or thought nothing that hasn’t been felt and thought by many others. Misery really does love company. Discovering the banality of one’s own pain can be a great comfort.
Depressed people should bear in mind that the bons vivants who can least abide their presence are likely to be depressive themselves, and afraid of contagion; the playground cruelty that refuses to tolerate vulnerability is a defence against vulnerability. But nowadays I generally find that it’s easy to talk about depression—as long as it is in the past tense. When I’m not depressed, I can go into excruciating detail, as I have done in this book and in my public lectures. When I’m depressed, though, I can’t tell people about it. It becomes suddenly shameful.
The absurdity of this reaction is not lost on me. This book has been published in twenty-four languages; it would be tricky to be much more public than I have been. Yet when I have to cancel a plan because of my mental health, I make up a litany of somatic illnesses, apologizing about mythic cases of flu or fictive sprained ankles. Six weeks later, I can admit to the people I’ve lied to that I was actually having a bit of a dip, but in the moment, it seems impossible to reveal. Partly that owes to the underlying fact that you have to be in a vigorous state of mind to shrug off depression’s stigma. I suffer a kind of internalized lunaphobia, a self-hating prejudice against mental illness; when I’m depressed, I think less of myself and see depression as a failure, though when I’m well, I know that’s nonsense. I also become weighed down by other people’s sympathy. Depression is an illness of loneliness, and when you are in it, you know your loneliness is unbreachable. People who want to comfort you are likely to be distressed if they can’t offer any real comfort. You feel guilty for putting them through that, though being abandoned would be worse.
Vice President Joe Biden recounted at the 2014 meeting of the American Psychiatric Association that a friend whose child was severely depressed had described that child as “floating into space at the end of a string.” The father had said he held the other end of the string and wanted to use it to reel in his son, but knew that if he pulled too hard, the string would break and his son would be lost for ever. So he was just holding on as best he could. Biden expressed a commitment to strengthening the connection, to making it safer and easier for all of us to reel in people with mental illnesses. Better mental health services, he said, would make the string less likely to break. When I met with him later, he averred that ending the prejudice around mental illness was one of the civil rights battles of our generation, and he praised the people who battle it. I remarked that as a person with a mental health diagnosis, I was grateful to him and said that I found it remarkably courageous for a sitting politician to champion such a stigmatized cause. “You are the brave ones,” he replied.
The uncertain hold on the string haunts relatives or friends of depressed people, who often ask me what they should do. I counsel them not to let the depressed person become truly isolated. Some depressed people want lively conversation, that confirmation of engagement. More find interacting burdensome; it’s a good idea to sit near them and keep silent. Some depressed people can’t bear to have anybody else in the room with them. Sit just outside the door. But don’t go away. The depression will only intensify in the private cocoons we spin at our lowest. Depressed people, too, should remember to avoid being alone to the extent they can. My other advice to friends and relations of people who are depressed is not to seem too scared of it. Other people’s fear can exact a terrible toll from the people who instigate it. And we’re not so frightening; I’m the same person depressed and undepressed. Mood is not character.
If it is shattering to know a depressed person, it can be more shattering not to know one. We like to think we can identify depression in those we love and funnel help towards them when they need it, but depression is often a closely guarded secret, invisible even to the knowing eye. On October 17, 2009, my college room-mate and lifelong friend Terry Rossi Kirk committed suicide. I have grieved ever since for the loss of that friendship and for the naivety that allowed me to presume from Terry’s invariably chipper demeanour that he couldn’t also be in the grip of depression. Depression expert though I profess to be, I misread the signs from Terry. Anyone who has loved a person who took his or her own life struggles to outpace the shadow of guilt. A suicide feels like the failure of a thousand chances to help, of everyone’s capacity to save the person who has died.
Terry’s other friends and I have agreed that we could not have changed his sadness, but I like to think we might have talked about the pleasure that can be wrought from sadness—something his ruthless merriment kept him from learning. We all might have reminded him that it is possible to be overcome with sorrow and still find meaning in that sorrow, reason enough to stay alive. The strange thing is that Terry was one of the people who taught that to me; our friendship was a long lesson in resilience. In my times of darkness, he was part of the scaffolding that held me in the world. I have to wonder through what random biology Terry didn’t make it, while I am still here. Were our depressions fundamentally different? Our attitudes towards them? Our therapies? Some of us are able to keep going; some can’t. None of us can presume that we will die only of natural causes. Terry believed that he had no one who would truly mourn for him, though he left behind a devastated life partner and a wide circle of grief-stricken friends, relatives, students and colleagues, who wish they had managed to make Terry feel as loved when he was alive as they love him in death. Depression is the loneliest possible fight.
Since this book was first published, in 2001, I have met thousands of depressed people. Some are receiving excellent interventions and doing well; a small number have genuinely refractory (treatment-resistant) depression and cannot be helped; some avoid seeking help because they dislike even the idea of it. Many, however, have taken the agonizing steps of admitting their mental illness and seeking treatment, but are still not receiving competent care. “I’ve tried so hard,” one confided to me after a lecture I gave in Denver. “If I kill myself now, no one can say I didn’t try.” He was following an inappropriate regimen, taking activating medication (a drug that hypes one up) for an agitated depression (in which one is too hyped up). Someone else at the same event complained that he had lost the will to do anything, then revealed that he was taking huge doses of sedatives. Many people obtain antidepressants from their primary-care physician, and while some do fine with a quick Zoloft or Prozac prescription, many others do not and require extended follow-up, dosage adjustments, and multiple medications.
Competence here requires a singular blend of science and art. Our understanding of the brain remains primitive at best, and psychopharmacologists of the first rank are still working on intuition and forced inspiration. Our therapies for mental illnesses are not very effective, cost a lot, and entail innumerable side effects. That said, recent progress in understanding the brain and combating mental illness has been dazzling. It’s a bit like space exploration: we know exponentially more than before we managed to blast off, but our advances have underscored how much there is to learn. Congressman Patrick Kennedy refers to it as “exploring inner space just like John F. Kennedy sent astronauts to explore outer space.” As someone who suffers from depression, I’m grateful that I live now and not fifty years ago, when the treatments that have helped me were unavailable. I hope, however, that people with my psychological profile fifty years hence will look back at my regimen and shudder at the idea that anyone had to endure such crude interventions.
I wish I had more encouraging news to report about what has been discovered in the past fifteen years. The so-called neurotrophin hypothesis of depression suggests that depression and stress lead to impaired neuroplasticity, and that antidepressant therapies—psychotherapy, medication, electroconvulsive therapy, deep brain stimulation (DBS) and even sleep deprivation—all raise levels of brain-derived neurotrophic factor (BDNF), which aids the formation of new neurons and the development of synapses. This is an important idea, but while it helps explain existing treatments, it has so far not been the basis for new ones.
A few more medications have been launched, and help some people who were not helped by what was previously available. These new drugs include Lexapro (escitalopram), a potent selective serotonin reuptake inhibitor (SSRI—the class of antidepressants that includes Prozac, Zoloft and Lexapro); Savella (milnacipran), an SNRI (selective norepinephrine reuptake inhibitor) similar to Effexor that is approved for treatment of fibromyalgia; and Brintellix (vortioxetine), an SSRI with novel serotonin-receptor effects that seems to work about as well as other serotonin drugs. There’s also Symbyax, a combination of Prozac and Zyprexa for treatment-resistant depression. There’s Viibryd (vilazodone), which works similarly to existing SSRIs, though it is claimed additionally to stimulate certain key serotonin receptors. And there’s Intuniv (guanfacine), used primarily for attention deficit hyperactivity disorder (ADHD) in children, which may have some effect on anxiety, especially in people with PTSD. Latuda (lurasidone) is an atypical antipsychotic that has been helpful to people in the depressive phase of bipolar illness. Some popular focus has turned to 5-HTP (5-hydroxytryptophan), which is sold as an over-the-counter nutritional supplement. While supporting research is lacking, I have corresponded with people who claim to have been helped by the supplement, which is a precursor to serotonin.
Depression that has not been ameliorated after at least two courses of evidence-based antidepressant regimen of adequate duration is classified as “treatment-resistant.” The U.S. National Institute of Mental Health (NIMH) has announced an initiative to identify “rapidly-acting treatments for treatment-resistant depression.” The most exciting prospect is ketamine, an anaesthetic and veterinary tranquillizer long sold on the streets as Special K. This drug blocks the N-methyl-D-aspartate (NMDA) receptor in the brain, a target no other drug has reached. All previous antidepressants have worked on dopamine, norepinephrine or serotonin; ketamine affects glutamate, the most common neurotransmitter in the human nervous system. It appears to have other effects, too, and it’s not clear which mediate depression; some scholars believe that its antidepressant effects may owe to its μ-opioid effects—in effect, to its similarities to morphine. Ketamine is both a stimulant and an opiate, echoing in part the effects of cocaine and amphetamines.
Ketamine has been demonstrated to be highly effective in people who are unresponsive to other medication, giving up to 70 percent of them relief. While the effects of more traditional antidepressants take several weeks to set in, ketamine works within hours, achieving full efficacy within a day and sustaining its effect for at least a few days in many patients; one in four still experiences some effect a month after administration, though the average relapse point is less than two weeks. Administration every few days can sustain the effect for a while. Suicidal thoughts tend to dissipate quickly on ketamine. The drug is usually given intravenously or as an inhaled mist; taking ketamine orally has not been effective for depression. The doses at which it affects depression are much lower than the doses used for anaesthetic or recreational purposes; it has, however, been used at higher doses as a supplementary anaesthetic for patients receiving electroconvulsive therapy (ECT).
Unfortunately, it is not viable for a wider part of the population. Too little glutamate function at the NMDA receptor can trigger psychosis, while too much can kill crucial neurons; furthermore, since glutamate affects learning, memory, cognition, perception and emotion, manipulation of it must be carefully weighed, and the potential for unwanted side effects is vast. Ketamine may also harm the kidneys and liver. Further, any drug already known for its recreational properties is particularly vulnerable to abuse. Historically, people with depression have not had long-term improvement from stimulants and opiates, so the question of when and how and with whom to use ketamine remains tangled. Because it is already approved by the FDA as an anaesthetic, it is easy to obtain, and there is some cowboy medicine being practised, with doctors commissioning pharmacies to compound home-made nasal sprays. The controlled studies of ketamine for depression are promising, but they are also limited. Alan F. Schatzberg, sometime chair of Stanford’s psychiatry department, has warned of a “slippery ketamine slope.”
Scientists have been seeking other drugs that would exploit the same pathways as ketamine. Among these is Rilutek (riluzole), a drug previously approved for ALS (amyotrophic lateral sclerosis); some evidence favours scopolamine, which is usually used to abate motion sickness. Additional research has focused on Glyx-13, which has a similar mode of action to ketamine, possibly without the danger of causing hallucination and psychosis; it is on the fast-track approval path at the FDA.
But the pharmaceutical industry has largely abandoned work on new psychiatric medications. Several that looked promising have failed clinical trials, and the sheer complexity of the brain has proved increasingly intimidating. The wave of Big Pharma optimism that followed the release of Prozac has dimmed, though Johnson & Johnson was recently given “breakthrough designation” by the FDA to develop ketamine as a patented nasal spray for depression—which means that approval would be significantly expedited, giving patients access to the drug (and the company access to profits) before it has endured the large studies ordinarily mandated for new pharmaceuticals. That exception notwithstanding, we have now exploited the basic insights about certain neurotransmitters reached thirty years ago and need another major innovation before we can sculpt alternative approaches. Researchers in genomics, epigenetics and electrophysiology are working with clinical psychiatrists in hopes of achieving it. The founding in 2007 of the Psychiatric Genomics Consortium indicates considerable sanguinity outside the commercial sector; the group works to identify the genetics of mental health, assembling massive amounts of research to create meta-analyses that may point towards associations between particular genetic variations and major mental illnesses, including depression.
While medication has stalled, research focused on electricity, light and magnetism has advanced, and both old and new methods are being used increasingly broadly. This disparity reflects both the dearth of pharmacological innovation and the bad press given to medication. It also reflects the view of depression as “a circuit disorder, not simply a chemical imbalance,” according to Thomas Insel, director of the National Institute of Mental Health. This reflects the increasing understanding of depression as a complex irregularity in the brain. Insel has observed that recognising depression as an arrhythmia is the most important advance in the field.
Electroconvulsive therapy has long frightened people both because it was crudely administered in the past and because it can cause memory loss. The use of a newly identified form of shock, ultra-brief pulse width, has ameliorated that side effect. Ongoing work seeks to make ECT—the most effective intervention we have for severe depression—less dreadful. There is slim profit motive for rejuvenating a procedure with such a troubled history. Its efficacy is still only a bit over 50 percent, and side effects are not trivial: I have met people who regret opting for ECT. But I have also met numerous people whose lives were saved by it. At present, too many depressives who might be helped by it refuse even to contemplate it. “ECT continues to be the most effective treatment for severe depression—no question about this,” Insel said. “Yet its use is decreasing, not increasing. Recent modifications have mitigated some of the adverse effects, but that has not altered the ‘stigma’ surrounding this treatment.”
Magnetic seizure therapy (MST) is a variant on ECT. Like ECT, it induces seizures, but because the skull does not impede magnetism the way it does electricity, the effects can be more precise. So whereas ECT tends to affect larger brain areas, MST can target a more specific area and thereby create focal seizures rather than a general brain seizure. It is clear, however, that inducing a seizure in one brain area affects many others. So even if a seizure is contained, its downstream effects may be broad. Early comparison studies seem to suggest that ECT and MST are comparably effective.
These are inpatient procedures, requiring anaesthesia and carrying side effects. In the wake of their advancement, transcranial magnetic stimulation (TMS) has had a comeback. This outpatient procedure depolarizes brain tissue by exposing it to powerful magnets. The patient puts on a sort of helmet full of magnets and is hooked up to a TMS machine, usually for a series of sessions designed to bring about steady improvement. Once the patient has emerged from depression, the procedure may need to be repeated for maintenance. TMS devices are being modified to enable physicians to control pulse shape, which has proved to be an important variable in ECT. How these treatments are best coordinated with pharmacological or talk therapy awaits further exploration.