“The truth will set me free. Budabudapup! Namaste. Someone told me that. Someone who was raped told me that. Budabudapup! I love everybody. Who drives the van? I don’t know. My truth will set me free. Am I house of spirit? Am I Sophie’s Choice? Who will ever know? . . . Budabudapup! Reboot!”
Johanna’s words come out rapid-fire, punctuated by the cartoonish robot noise she repeats over and over. Wearing a NASA shirt and a clear plastic bag tied around her entire body below the neck, the young white woman with cropped reddish-brown hair and freckles sits in a waiting area of the psychiatric emergency department of LAC+USC Medical Center, one of the largest and busiest public hospitals in the United States. When the police ask her if they can take off the handcuffs (that she had requested they put on her), she refuses. “Nope. Not right now.”
A first-year psychiatry resident begins the intake. “All right, Johanna, did you take any drugs today?”
“No. I have too much energy,” she replies, kicking her legs in the chair, arms still handcuffed behind her back. “Budabudapup! I saw Michael Jackson die. Budabudapup! I am not who I am. Do you understand? When you look at your shit you will know. Rihanna, you are not the truth, and neither is Oprah for being O.”
“Have you ever been on medication before?”
“Lots.”
“What kind?”
“Every single one prescribed by my doctor. The. Rapist. What does that stand for? Therapist. Spell that out.”
The doctor asks if Johanna wants medication to calm her down, but it isn’t really a choice. As ED staff holds her arm to give her an injection, she yells, “Nope. Get the fuck out of here! No, no, no. I don’t trust. I refuse—get the fuck off of me!”
Johanna gets “the usual” for agitated patients, informally called “the cocktail”: a dose of Ativan, a benzodiazepine to calm her to sleep, and an antipsychotic to stop the delusions and hallucinations. Johanna needs a break from her illness, and the cocktail will quickly do the job. It will also help the doctors do their jobs. With the psych ED running at as much as 200 percent of intended capacity, the best patient is one who is calm, cooperative, perhaps even asleep.
Johanna has bipolar disorder with episodes of mania and depression. Today, she is in a manic phase, unable to shut down the engine of her racing mind. Sleep is difficult to impossible. The cocktail calms her, as intended, and staffers roll her in a gurney to a spot against the wall where she sleeps alongside other patients.
My first good look at the psychiatric emergency department at LAC+USC came in October 2012. I had been exposed to similar EDs, but none that compared to this six-hundred-bed teaching facility with thousands of employees, connected to the highly regarded Keck School of Medicine at the University of Southern California. Located in a lower-income, predominantly Latino community called Boyle Heights in downtown Los Angeles, an eight-minute drive southwest to skid row and a six-minute drive west to the county jail, the hospital serves rich and poor, students and homeless people, those with insurance and those without. Once operating out of the Art Deco building dubbed the “Great Stone Mother” that was featured in the opening credits of General Hospital, the current medical center is a 1.5-million-square-foot complex of three linked towers, organized around a campus complete with pedestrian plazas and gardens.1 The emergency department takes up the lion’s share of space, and to the right of the emergency entrance, through a set of locked doors managed by an attendant, one enters the world of twenty-first-century emergency psychiatry.
The first time I set foot inside a psychiatric emergency room was in 1980, during my second year at medical school in New York City. My job was to shadow Dr. Calib, a brilliant psychiatric resident who worked the night shift at Bronx Lebanon Hospital. Before we even shook hands, Dr. Calib asked if I was hungry. “Not really,” I answered. “Well, here’s the thing,” he said, “when you’re in an emergency room, if there’s ever a chance for you to eat, you eat.” We got Chinese takeout from a place under the elevated train, during what indeed turned out to be our only opportunity for dinner. When we returned, I was quickly surrounded by insanity like I hadn’t seen since I’d lived with Merle. One patient, who was tied to a gurney, managed to free one hand and reach a shelf of vials, pills, and equipment, sweeping it all to the floor. Another patient had set his apartment building on fire. “I like to see the flames,” he explained. A half-dozen other consults kept us running from room to room.
At eleven o’clock, Dr. Calib “signed out,” downloading information to the incoming psychiatrist as part of the shift change. He mentioned the patient’s “I like to see the flames” comment. Hearing Calib relate the patient’s absurd explanation caused some floodgate to burst open, and I had to excuse myself. Out in the hallway, behind the closed door, I burst into uncontrollable, horror-stricken, nervous laughter. I couldn’t understand how the residents kept it so cool. I finally composed myself, went back in, and apologized. “He’s okay,” Dr. Calib said to his colleague. “First night.”
But nothing would discourage me from becoming a shrink. No other profession seemed remotely possible. No other field held any appeal.
During those years in med school, I had no interest in the microscope. I loathed the cadaver and gave up meat for a year to avoid being reminded of him at mealtime. I hated killing the dog to study how the heart stopped. I was bored by the forays to the hospital to do “cool” procedures like inserting a central line into the internal jugular vein. Instead, I started making documentary films about patients with schizophrenia. I took courses at nearby film schools, to connect me to what I loved doing—talking to and trying to understand people like Merle. My parents, who had never liked my choice of specialty, didn’t know what to make of me. “If you want to make films, maybe you should become a radiologist?” my mother suggested.
For my psych residency, I moved to Los Angeles for what struck me as the nation’s best training, at the University of California Los Angeles (UCLA) Neuropsychiatric Institute. There, working at one of the largest Veterans Administration (VA) hospitals in the country, I began to understand more deeply the complexities of treating SMI thanks to my first teacher, psychiatrist Theodore van Putten, MD. Dr. van Putten was a fastidious and impeccably dressed man with wire-rimmed glasses and a bow tie. I studied him as much as I did the patients. During early-morning rounds, when patients lined up to talk with him, he would ask, “What’s your problem?” After a minute of listening to their complaints, he would dictate their medicine changes to the nurse, then snap, “Next.” (I witnessed one patient with schizophrenia throw a trash can after rounds because he felt so disregarded.) Then there was Dr. van Putten’s practice of drawing straws. In the 1980s, many people who had taken antipsychotic medicines for decades developed a neurological condition called tardive dyskinesia, characterized by disabling, disfiguring, and irreversible movements of the tongue, arms, and feet. As part of his research on reducing medication quantity to determine the minimum effective dosage and cut down on side effects, Dr. van Putten would have the residents literally draw straws to determine what dosage he’d dole out to each patient who agreed to be part of his research program. The shorter the straw, the lower the dose. Dr. van Putten took careful notes of the results. This randomized research changed the course of prescribing antipsychotic meds: less can be more. He discovered that lower doses often got people better than higher doses, with fewer side effects.
One day I saw him picking trash off the floor, tidying up the hallways for the patients and the visitors, and realized that despite his bullish demeanor, Dr. van Putten cared deeply about his ward and its patients. He wasn’t a bleeding heart like most of my other liberal mentors, but unlike all my previous teachers, he was giving blood every day. He was the very first doctor I had ever met who’d dedicated his entire professional life to working in the trenches with the patients who needed him the most: those with schizophrenia. He didn’t have a fancy office, just a back room in the VA where he treated patients, day in and day out. The work he did was transformative, launching a legacy of schizophrenia research in Los Angeles and improving the prescribing of antipsychotic meds for millions of people.
Still, I always wondered how this brilliant, dapper, sophisticated man with a taste for the finer things in life ended up spending his days treating the sickest people in a corner of the VA hospital until his death in 1993. Not until I spoke to his protégé and his widow for this book did I learn that Dr. van Putten had a sister with schizophrenia.
Almost thirty years later, Dr. McGhee, a doctor in the LAC+USC psych ED, is trying to teach her residents how to make the right decisions for the right reasons when prescribing antipsychotic meds. The young resident caring for Johanna tells her: “She’s presenting with lack of sleep, distractibility, grandiosity, most recent episode: manic.”
Bipolar disorder is diagnosed based on a cluster of symptoms developed by psychiatrists in the twentieth century, among them the frenzied, erratic, tangential speech with a constantly shifting focus that Johanna displays, which psychiatrists call “pressured speech.” Other symptoms include periods of marked, elevated, expansive, and grandiose moods with boundless, irrational exuberance and confidence. With mania or hypomania (a less extreme form), people experience periods of euphoria, high energy, sleeplessness, or unusual irritability.
Interspersed with periods of elevated moods are the normal or euthymic moods that affect some people with bipolar disorder, along with the plummet of depression. The depression side of the disorder leaves people feeling low and hopeless, often paralyzed by a sense of defeat, blinding pessimism, and fatalism. It also often includes distractibility, slowed thought (so much so that it may be confused with dementia in the elderly), lack of energy, and a loss of interest in the joys in life, including a shutting down of the person’s drives for sex, joy, love, health, and food. Bipolar disease can exist with or without losing touch with reality, aka psychosis.
“What do you want to start her on?” asks Dr. McGhee.
“I was thinking Seroquel maybe,” says the resident.
“Because . . .” prompts the attending.
“Because at the APA conference they had a study that showed that Seroquel as a stand-alone medication seemed to work very well for the bipolar patients.”
The attending prods for more information. “If you would like to start her on Seroquel, that’s fine. What would be the downside?”
“It could cause hypotension.”
“It’s going to be very sedating. Some people—boom!—they’re on the floor with it. And some people not. I don’t know with her. It’s going to be a guess.”
“You want to know what I learned from the drug rep people?” asks the resident, referring to pharmaceutical representatives who hosted the seminar she attended at the APA’s annual meeting.
“Okay, yes.”
“They said to start on, for people who are manic, start with like two hundred on the first day, and then increase to, like . . . They said increase gradually so on the fourth day you’re on six hundred.”
“Think about what their incentive is,” cautions Dr. McGhee, “versus what we need to do for the patient.” McGhee waits for a nod and then continues her Socratic lesson: “What are the major side effects of Seroquel?”
“Metabolic effects.”
“Yes, and Seroquel is super high on that.”
“And she’s, like, a young lady—”
“She’s a young lady. We don’t necessarily want to fatten her up, but also, we’re not necessarily deciding on her long-term meds. But it’s important to be aware. That’s all I’m saying. Those are some of the conversations you can have in your head about why this versus that one versus the other one.”
Johanna is just one of ten million Americans diagnosed with psychotic disorders who need expanded medication options. Richard Friedman, MD, director of psychopharmacology at the Payne Whitney Psychiatric Clinic, tells me that “fifty percent of people at the end of a year stop their treatments, either because the drugs don’t make them feel better or they can’t tolerate their side effects.” Make no mistake about it. On balance, these medicines save lives and are essential for most people to get better. But they are also undoubtedly problematic. According to the Substance Abuse and Mental Health Services Administration (SAMHSA), up to 83 percent of people with SMI are overweight or obese.2
The resulting sedation and low self-esteem makes people eat even more, compounding their risk for diabetes and heart disease. They experience a disproportionate number of early deaths, with a reduction in life expectancy of up to twenty-five years, partly as a consequence of type 2 diabetes and cardiovascular disease.3
Seroquel, the trade name for quetiapine, is among the atypical, or second-generation, antipsychotic agents marketed in the late 1990s after the release of clozapine broke the “new medication barrier.”4 In Europe in the late 1950s, researchers discovered that clozapine functioned effectively as an antipsychotic without causing one of the dreaded and sometimes fatal side effects of existing (first-generation) antipsychotics: a medication-induced fever and delirium called neuroleptic malignant syndrome. Before clozapine, doctors had relied on traditional drugs such as chlorpromazine, the first blockbuster antipsychotic,5 or haloperidol (brand name Haldol), a chlorpromazine analogue released in 1958.6 Although these earlier drugs did bring about symptom improvements that allowed many patients to leave institutions, treatment in 40 percent of patients came at the high cost of debilitating and permanent side effects, like extrapyramidal syndrome (EPS), which is characterized by Parkinsonian-like movement disorders.
Enter the second-generation antipsychotics—clozapine, olanzapine, quetiapine, and risperidone—currently used to treat schizophrenia, bipolar disorder, major depressive disorder, and schizoaffective disorder. They were first marketed in the late 1980s and 1990s as being comparably effective as traditional antipsychotics without causing movement disorders.7 Research has confirmed that these medications can also work for the mania of bipolar disorder.8 They also have the potential to cause extreme weight gain, diabetes, and some of the same debilitating movement disorder side effects as the older drugs.
Steven Hyman, MD, one of America’s most distinguished research psychiatrists, recalls when he entered the field in the 1980s: “It was quite clear that the vast majority of patients with serious psychiatric illness were at best only partially helped by all of the existing treatments.” Like many psychiatrists, he was hopeful that a sea change was coming. During Dr. Hyman’s tenure as director of NIMH from 1996 to 2001, he oversaw the comparison of old versus new drugs, finding that “tragically, the second-generation antipsychotic drugs other than clozapine [a drug we’ll discuss further in the coming pages] were not all that much better.” In fact, the newer antipsychotics cause more weight gain than the older options.9
Now, four decades into his medical career, Dr. Hyman serves as director of psychiatric research at the Broad Institute of MIT and Harvard. He laments that none of the promise of new, better drugs has been realized, and that the diagnostic system of the twentieth century “turned out to also be a mirage—so fundamentally flawed that it actually probably served to impede research” by making it confusing for scientists to study the diseases based on such inaccurate clustering.
A year after her stay in the LAC+USC psych ED, I visit Johanna in the single-story, pale yellow house where she lives with her dad. Their backyard is a green oasis. Behind the picnic table covered in bright flowerpots, her dad keeps painted lady and monarch butterflies in a screened-in porch, and as we chat Johanna carefully tears open a series of wax-paper envelopes, releasing the colorful insects one by one. The topic quickly turns to meds. She’s been hospitalized ten times in the past year but has recently stopped taking the mood stabilizer and antipsychotic drugs she’s been prescribed. “So, it’s been about three or four months and I find that I, personally, function better off medications.”
“I think your mom felt really strongly that you take your medication,” says her dad, a cheerful, middle-aged man with white hair and dark eyebrows. “I just wanted to be sure what was the right thing for you. We don’t know the side effects that they give you.”
Johanna tries to explain. “I didn’t say, like, ‘I’m not going to take medication. I don’t need it.’ It was, ‘Okay, the medications are making me worse, so let’s try it without it.’ I mean it’s very weird to go into a hospital and then the pills have the opposite effect. Everyone’s different. Every body, every person is going to have different reactions. I wish it was that simple for me. Like, ‘Ah! You know, I found this pill and it worked.’”
Johanna, now twenty-three, has been hospitalized more than a dozen times since her first manic episode at age nineteen. Her treatments have included multiple medications aimed at staving off more manic episodes. The cycle of antipsychotic drugs and untreated mania that she describes illustrates the dilemma facing many people with SMI. “When I start to have my mental break, my mind starts to feel like it’s turning to mush,” she says. “You know how, like, when you see apples or like a pear or something, and they’re rotting and they’re mushy and they sink in? That’s how I feel. That’s how my brain feels.” As the episode sets in, she stops being able to function normally. “I’m talking really fast, and I can barely sit still, and . . . and getting manic.”
But the medications often make her feel worse. “For me, it feels like with each new pill you get a whole new version of craziness.” Johanna describes the shift from “talking and screaming and feeling like I have all this energy” to “going really slow,” to the point that she can’t talk and winds up stuttering, just trying to get the words out.
Those are just the mental side effects. While taking the antipsychotic medication risperidone, Johanna experienced a choking sensation that would come and go. “My neck would stiffen, and I was like, ‘Why am I trying to kill myself? Why is my body literally trying to kill itself? I cannot breathe; I’m choking.’” And then she began lactating—a relatively uncommon but known side effect of risperidone, which can disrupt the reproductive endocrine function in women, sometimes raising the hormone prolactin that triggers the breasts to produce milk. And that is “not a benign issue,” Lee S. Cohen, MD, director of the Center for Women’s Mental Health at Massachusetts General Hospital and professor of psychiatry at Harvard Medical School, tells me. On the contrary, by “turning off reproductive endocrine function and estrogen, [the drug-induced prolactin increase] puts women at risk for early onset of osteoporosis and a whole host of other problems.”
But avoiding her meds is also not working in Johanna’s favor. Six months after my first visit to her house, she’s in trouble and has called for a ride to the hospital. Her father had gotten sick and could no longer live at home. Johanna comes to the door in a boisterous mood, carrying a ’76 American flag on a metal pole with an eagle on the top and wearing bright pink lipstick, sparkling gold eye shadow, and a red bandana. Her face and chest are marked up with black and red doodles made in marker or lipstick: stars, hearts, a hash mark, the word Respect written in reverse just below her collarbones.
“It’s a mess.” Johanna sweeps her arm in the direction of the living room behind her. “This is about to get bad,” she says with a strained laugh. “But that’s how things get better . . . so . . .” Inside, the house is littered with bags, boxes, food, a half-empty water bottle, a set of golf clubs. Towels and clothing, piled high, sit alongside cardboard boxes, some taped and labeled, others open and spilling over.
“Trying to clean it,” Johanna explains. “And I made it worse because I’m like, ‘You know what I’m going to do? Just take it all out and then we have to deal with it.’ And now I can’t deal with it.” She laughs, but it doesn’t hide a flash of despair in her eyes before she shifts back into tour guide mode, pointing out landmarks in the terrain of her turmoil. Her NASA shirt hangs down her back like a cape and a plastic bag is tied around her arm. At breakneck speed, she says, “It’s been bad, but it’s been good because you have to have the bad times to recognize the good times. The light to rise, wake up! The darkness to slow down, regrow, to up, down, up, die, live, bipolar. I think we all are and it’s a blessing, it’s a curse and a blessing. It’s yin and yang.” Demonstrating the rapid cascade of loosely connected ideas that can come with mania, Johanna says, “There’s a Japanese art form where when something cracks you fill it in with gold and it becomes better, stronger, faster—Kanye West—the robots.”
Passing through the kitchen, which is strewn with dishes, cans and bottles, coffeemakers, cleaning products, and a half-eaten pizza, Johanna describes her latest regimen: “Water, then orange juice, melatonin—so not Xanax or anything like that. Can’t do antidepressants, even when I get depressed. Then I try to go more vitamin C, oranges, sunlight.” Raw meat sits atop a platter on the windowsill. “Look at this nasty food: this pizza from last night, which I still haven’t eaten. I can’t even feed myself.” She flaps her arms like wings. “I don’t know why. This is why I can’t get better. Antidepressants that are supposed . . . they crack, triggered the bipolar, which becomes amped-up psycho and makes it worse. I need to sleep,” she concludes. “I don’t know the last time I’ve slept.”
Johanna packs her bags and slings them over her shoulder. In the car en route to LAC+USC’s psych ED, fifty miles away, she explains how she’s lost her job. Her boss kept calling to give her shifts but she eventually stopped returning the calls or showing up. Then she didn’t have money to pay her phone bill. She scrunches her face, holding back tears. “I’m trying to, like, go to school, and shit keeps knocking me fucking back. Everything that’s supposed to get me ahead is knocking me back.”
Reaching LAC+USC at last, walking across the hospital’s pedestrian bridge, Johanna seems relieved. “It’s motherfucking nappy time.” No doubt the doctors will offer her the “cocktail” that will help her sleep, but, as always, her relief will only be temporary.
“The brain does not give up its secrets easily,” says Dr. Friedman. This presents significant obstacles to the discovery of new mechanisms for treating mental illness. Because researchers have struggled to identify new molecular targets, individuals with SMI—as well as the doctors who treat them—are left to make do with “me-too” drugs. It takes billions of dollars to develop effective medications with fewer side effects, and the failures of multiple expensive studies have led the pharmaceutical industry to pull back on neuropsych research altogether. “A number of very large drug companies have withdrawn from looking for new treatments for psychotic illness, which is very, very consequential for the field,” says Stephen Marder, MD, professor and director of the section on psychosis at the Semel Institute for Neuroscience at UCLA. As a result, there “hasn’t been a blockbuster drug in psychiatry for decades.”
Without research that might identify novel molecular targets in the brain, many pharmaceutical companies are left to work with the same compounds discovered in the 1950s and 1960s, tweaking them to work slightly better or marginally reduce side effects. The business model is, as Dr. Friedman explains, to make as much profit as possible before their patents run out (which can happen quickly given that the clock starts ticking when the drug is created, before it undergoes years of testing and then is brought to the marketplace). As a result, today’s antipsychotic and bipolar medications are much safer, are more tolerable, and have fewer side effects, yet they are no more effective in eradicating symptoms, and we are no closer to a cure. Dr. Friedman explains it this way: “The risk-averse pharmaceutical industry takes a known compound with a known mechanism of action and modifies it just slightly to get a ‘new drug.’ So, you have lots and lots of what we call ‘me-too’ drugs that are new, they’re patented, but they work on exactly the same targets as the old drugs.”
In Scientific American, Edmund S. Higgins, clinical associate professor of psychiatry and family medicine at the Medical University of South Carolina, offers this analysis:
As it turns out, drugs developed in the past twenty years perform like older medications. Abilify is no more effective for treating schizophrenia than the very first antipsychotic, Thorazine. New antidepressants lift mood no better than the tricyclic antidepressants discovered in the 1950s. Lithium, first used in 1949, remains the gold standard for bipolar disorder. Adderall provides no further advantages for attention-deficit/hyperactivity disorder than the Benzedrine first administered for it in 1937.10
Over the course of my career, I have seen better medications and greater access to care for many patients. But innovation is lacking. As a society, Dr. Friedman explains, we have decided to leave most of the research, development, and testing of medications to the for-profit pharmaceutical industry, rather than to NIMH or other government agencies. Since the brain is so hard to understand and so hard to study, we need much more investment aimed at identifying the basic mechanisms and circuits involved in psychiatric illness. But “that is not something the drug companies are going to spend their money or their time doing,” he cautions, laying out the scope of our predicament:
We don’t need fifteen SSRI antidepressants. We don’t need twelve new atypical antipsychotics all doing the same thing. What we need are new drugs that act in different systems and different chemicals in the brain and different circuits. That’s the crux of the problem in discovering new drugs for psychiatric disorders because in order to do that, you need basic science understanding of psychiatric illness. . . . That’s something that basic science researchers in universities are going to do, make discoveries that are interesting about the targets for psychiatric disorders, identify targets, synthesize new drugs, and go to the drug companies and say, “Guess what, we found a fascinating new target. We understand something about schizophrenia or depression that we didn’t before, and now we want to partner with you and we want you to go ahead and make and test this.”
One researcher who is working to advance our knowledge as a means of improving care and treatments for people with SMI is Lisa Dixon, MD, MPH, an internationally recognized scientist and clinician who has received more than twenty-five years of continuous funding from NIMH as well as the VA. Her studies have focused on advancing treatment engagement and adherence, improving quality of care, and reducing the negative impacts of co-occurring substance abuse addictions.
I first met Dr. Dixon in 1988 when I was a third-year resident unpacking boxes in my new office at the New York Hospital–Cornell University Medical Center (NYH-CUMC) after my transfer from UCLA. She was a year ahead of me. After making our introductions, she said, “We have something in common. We both have a sibling with schizophrenia.” I stopped short. Someone had divulged the confidential information that I’d disclosed only in my interview—a secret I rarely shared with anyone, much less my colleagues. I must’ve turned white.
“I guess I said the wrong thing,” she said, apologizing. Shit, I thought, my secret is out. I couldn’t stop that. But to make the breach feel less real, I avoided Lisa. We didn’t exchange another word for more than thirty years, when I reached out to her for this book.
Dr. Dixon is among the world’s leading psychiatrists for people with SMI. A professor of psychiatry at Columbia University Medical Center and director of the Division of Behavioral Health Services and Policy Research, she also serves as editor in chief of Psychiatric Services, the most important medical journal for daily care of people with SMI. She directs the Center for Practice Innovations (CPI) at the New York State Psychiatric Institute and leads OnTrackNY, an early-intervention program aimed at reducing disability in people experiencing their first episode of psychosis.
Forty years ago, her brother developed schizophrenia. According to their mother, Jacqueline, Sam had been a sweet, bright child. She noticed the first sign of trouble after he returned from an eight-week bicycle trip in Ireland between high school and college. “When he came back there was an almost imperceptible difference,” Jacqueline tells me. “I can’t even describe it.” Then, after his first term in college, Sam’s academics began to decline. He came home every weekend and didn’t seem to have made friends at school. He began “doing things in excess,” like drinking massive amounts of water or walking the dogs for inordinately long periods of time. “His behavior was not like a normal twenty-year-old,” she says, “and we didn’t know what to make of it.”
At this point Sam still had reasonable social skills, and his symptoms were at a low, manageable level—what is called the prodrome or precursor of the fulminating illness. But when he went off to medical school, his behavior grew increasingly disturbed. He never did laundry; he played basketball at odd times of night. He wound up repeating a year, and before long the medical school dismissed him. Jacqueline learned later that his bizarre mannerisms at both college and med school had been widely known to his teachers and peers, but no one had ever informed her or expressed any concern. Had his family known earlier about his decline, she believes they might have been able to help him more quickly. At home, he began having near-physical fights with family members, which was completely out of character. He was drinking eighteen glasses of water a day and became paranoid that the gardener, along with planes overhead, were after him. Then he stopped eating and became catatonic. He was hospitalized for the first time in 1981.
Through helping to manage her brother’s treatment, Dr. Dixon quickly learned the value of having a doctor who cares. “He had some hospitalizations. He had some wonderful psychiatrists; he had some psychiatrists who weren’t communicative at all. We learned—and I always say this to the psych residents—that the power of a kind, communicative psychiatrist is so much beyond what you could even imagine.” Despite her brother’s declining condition, her family never gave up. They confronted it head-on, seeking help down every avenue. Dr. Dixon approached the head of mental health services for medical students at the training program where she was a first-year student: John Talbott, MD, who, as luck would have it, was a pioneering advocate for those with SMI. Dr. Talbott worked with Dr. Dixon and her mother, offering them an education that would serve as a model for the type of interventions that Dr. Dixon would come to promote professionally.
Even so, nothing worked. “My brother has a greater severity of illness than probably the average person with schizophrenia,” she tells me. He was paranoid and unable to conform to the norms required of him in a group home where, as she explains, “you have to have breakfast when basically everybody else is having breakfast,” for example. “My brother didn’t like that life.” The only possibility was hospitalization—until he started taking an antipsychotic introduced in the United States in the 1980s called clozapine.
The results were transformative. “My brother did very, very well on clozapine; he was out of the hospital, he was functioning,” says Dr. Dixon. Although he was still unable to work, “you could talk to him about the basketball game, you could play Ping-Pong. He really just became himself. He became my brother again. He didn’t have a job, he didn’t get married. None of those things. But he seemed to be happy. He became more like the person I knew, a very gentle, kind of unassuming guy.”
Doctors live in fear of their prescriptions resulting in deadly side effects and always want to operate in accordance with the “First, do no harm” promise of the Hippocratic oath. When a blood test result raised concerns that Sam might have developed a potentially fatal side effect, he was taken off the drug. Called agranulocytosis, this side effect of clozapine causes the immune system’s white blood cells to shut down. Once Sam was off the drug, his subsequent mental decline was rapid. “He was horrible. He was as sick as I’ve ever seen him. He was disorganized, paranoid, and had no interest in basketball.” After his doctors determined that clozapine was not causing agranulocytosis, Dr. Dixon and his mother convinced them to put him back on the drug that had helped him so much. Unfortunately, as sometimes happens, he never recovered to the same degree. “He just never really was able to rebuild his life after that,” Dr. Dixon tells me. To this day, he occupies a long-term bed at one of the nation’s few remaining state institutions. Now sixty-one, he is unlikely to ever recover without a major breakthrough in treatment options.
One of the differentiating features of clozapine, first synthesized for psychiatric illness in 1958, sold in Europe in 1972, and finally marketed in the United States in 1990, was its effectiveness for the 30 percent of people with schizophrenia who are “treatment refractory,” meaning that they have not responded to three trials of antipsychotic medications from at least two different classes.11 This meant that clozapine could ease the symptoms of many of the sickest patients whose condition had, before the drug, been only marginally improved, or not at all improved by treatment. It also effectively managed what psychiatrists refer to as the “negative” effects of schizophrenia—cognitive deterioration and social withdrawal—and not just the “positive” symptoms such as hallucinations and delusions. As John Crilly writes in his history of the medicine, clozapine “forced the psychopharmaceutical industry to move forward into the twenty-first century,” while also giving “another group of people suffering from severe, treatment-refractory schizophrenia hope for a better quality of life.”12
I learned more about this transformative drug from Dr. Dixon’s husband, Donald Goff, MD, professor of psychiatry at NYU School of Medicine and director of the Nathan Kline Institute for Psychiatric Research. For the twenty-five years before he moved to New York City, Dr. Goff had been director of a community mental health outpatient clinic in Boston associated with Harvard Medical School that was one of the leading centers of its kind. He has studied clozapine for nearly three decades, in both laboratory and clinical settings.
He tells me that for many doctors, prescribing clozapine seems like “too much trouble” because of the monitoring necessary to protect against the agranulocytosis that’s estimated to occur in 1 to 2 percent of treated patients.13 Patients on clozapine require weekly blood tests, and this level of sustained care would be difficult for anyone who isn’t in an inpatient setting but is particularly difficult to manage with folks with SMI. Regardless, Dr. Goff says, compared to high-risk cancer treatments, for example, clozapine is relatively safe. And given the remarkable results he’s observed, he thinks it should be much more widely prescribed. “A third of all of our patients were on clozapine,” he says. “For many of them, it changed their lives. It allowed chronically hospitalized people to be discharged. It allowed people who were chronically suicidal or aggressive to have that under control.” Among his several hundred clinic patients taking the drug, roughly half improved, and very few wound up hospitalized, although many still had some psychotic symptoms. “It seems to protect people from relapse and exacerbation. It decreases hospitalizations probably for life,” he says. He is such a believer in the drug that despite the high-stakes side effects, he tells me that “if someone continues to have psychosis with the other antipsychotic drugs, it’s bordering on medical malpractice to not offer clozapine.”
But Dr. Dixon, who oversees hundreds of providers, understands the dilemma that a drug such as this one creates for doctors in the trenches. Imagine that you’re a psychiatrist with a caseload of five hundred or one thousand SMI patients, she says. You don’t want patients on a drug that requires such close monitoring, especially when many patients are unreliable about keeping appointments.
To me, it seems remarkable that a drug discovered sixty years ago, which has all this health, administration, and oversight baggage, remains the gold standard for effectiveness. Six decades later, it’s equally dumbfounding that we still don’t understand why clozapine is more effective than other drugs. Given the woeful state of psychopharmaceutical research today, Dr. Friedman rightfully calls for “much more basic science in terms of the basic mechanisms and circuits that are involved in psychiatric illness.”
Meanwhile, people like Johanna have to make do with the available treatments. Five years after we first met, Johanna says, “I finally realized that I do have bipolar. You know, a lot of people don’t need to be on meds, but unfortunately I’m not one of them.” She has also come to recognize that her relapses are part of her disease. Instead of being a reason to stop taking the drugs prescribed to her, it’s a sign that it’s time to adjust the dosages. And she’s doing her best to cope with the significant side effects. “The Zyprexa makes me so hungry. I feel like a bear that has just this never-ending appetite and I just eat big portions,” she says. “I think big can be beautiful. But for me, at this size, even standing too long or walking short distances, my back hurts. Even when I go on my walks—when I try to do what it takes to feel better—I feel worse, like my back just hurts so I have to stop a lot.” The meds also make it hard for her to focus. “It’s like I have ADD. It’s hard for me to pick up a book and read, and I’m a huge reader. But it keeps me stable.”
Despite having come to accept her condition, Johanna is distressed that she can’t really function in the world or be independent. “It’s my twenties. I’m supposed to be alive!” She tells me she plans to update her résumé and apply to the dollar store across the street, maybe even return to school. But she worries that anyone who knows about her situation will look down on her. “I feel like someone’s gonna be like, ‘Oh you’re a societal mooch. You mooch off your parents. You mooch off society. You mooch off the school.’ And I’m trying so hard. When you saw me the very first time where I’m wearing the trash bag and stuff, I was working two jobs and going to night school. I’d already spent two years at a homeless shelter trying to get work, trying to save up, going to therapy, trying to work, and I couldn’t do it.” She recognizes how hard it is for others with mental illness who may not have had the same privileges as she has. “I’m college educated. I don’t have any [physical] disabilities. I don’t have racism going against me. I don’t have a violent background. I didn’t grow up with parents who beat me or anything,” she explains. “If I can’t make it, what about everyone else?”