At some point that fall, I realized I had not experienced a full-blown panic attack since I’d started on Paxil in April—by far my longest such stretch since middle school. I was experiencing less anxiety, feeling productive and engaged in my work, and enjoying an active social life. My stomach settled. Paxil was magic.
Or was it? Because what was cause and what was effect? That promotion I got at work came along after someone left and I was elevated to fill the position; that would likely have happened even if I hadn’t gone on Paxil. Maybe that small boost in my professional status, along with the more interesting and empowering day-to-day responsibilities of the job, bolstered my self-esteem, which in turn gave me the confidence to start sending out freelance work, which in turn made me feel professionally engaged. And while I felt like the Paxil had somehow given me the strength to finally break the stubborn cord of neurotic codependence that had tied me to my girlfriend, maybe I would have done that anyway—and there is no question that, Paxil or no Paxil, being out of that relationship was liberating. (For her, too, I’m sure; we haven’t spoken since.) So maybe it was the particular constellation of events that came together that spring—the promotion, the breaking off of a dysfunctional relationship, the end of a dark Boston winter and the arrival of spring—that lifted my anxiety and depression. Maybe Paxil had nothing to do with it.
But I think it did. Beginning with that brief manic boost, my lived experience felt like it was Paxil inflected—and I now know that my clinical trajectory (mild mania, lifting of mood, effecting of positive life changes) is a fairly common one. Of course, another possibility is that what I enjoyed that spring and summer was the placebo effect—the Paxil worked because I believed it would work. (With the placebo effect, the power of belief itself, rather than the chemical content of any medication, is the salient mechanism.)
But the Paxil was not magic—or if it was, its magic ran out. Because after trundling merrily along in medicated contentment for ten months, my short-lived feeling of invulnerability was punctured within a period of ten minutes.
In those first months on Paxil, I had—for the first time in twenty years—been able to fly with only moderate anxiety. So one February morning, I drove heedlessly through a fierce New England rainstorm to the airport (how nice not to be in a nervous swivet for days before every plane ride!), boarded my flight, and settled in with my newspaper for the hour-long trip to Washington, D.C. I can’t say that I was ever, even in those glorious early days on Paxil, free of flying anxiety. But it was a gentler experience, manifesting itself as butterflies in my stomach, sweat on my palms, and a mild feeling of apprehension—what I imagine many people feel upon takeoff. So there I sat, twenty-eight years old, feeling relatively competent and grown-up (Here I am, I thought, the executive editor of a magazine, flying to Washington on business, reading my New York Times), confidently insulated from terror by my morning dose of twenty milligrams of Paxil, that little pink pill that had kept me panic-free for a blissful few months, as we taxied and took off.
And then, passing through the dark clouds that were producing the rainstorm below, we ran into turbulence.
It lasted all of ten minutes. Fifteen at most. But the whole time I was convinced we were going to crash—or, worse, that I would get airsick and throw up. Hands shaking, I gulped two Dramamine. Beverage service had been suspended—the flight attendants had been asked to stay seated, which terrified me. But as I looked around the cabin, none of my fellow passengers seemed unduly perturbed. To my left, a man tried to read his newspaper, despite the thrashing and dipping of the plane; to my right, across the aisle, a woman appeared to doze. I, meanwhile, wanted to scream. I desperately wanted the turbulence to end (Please, God, please make it end now and I’ll believe in you and be good and pious forever) and the Dramamine to take effect, and I craved, above all, unconsciousness, an end to the misery.
Of course, my fears of crashing must not have been completely consuming, because I had, even in that moment, an additional worry: Was my panic so obvious that the other passengers would see it? Logically, one anxiety should have canceled out the other: if we were all going to die, I shouldn’t have been worried about an ephemeral moment of earthly embarrassment before plunging into eternal oblivion, right? On the other hand, if I was going to end up embarrassed after the flight, that would mean we weren’t going to die, right? And at that moment, to be safely on the ground and to not be dead—no matter how embarrassed—was a condition greatly to be desired. But in my amygdala-controlled brain, with my sympathetic nervous system on full alert, there was no room for such clarity of logic. All I could think was, I’m going to throw up and I’m going to be humiliated and I’m going to die and I’m terrified and all I want is to be out of this situation and never to get on a plane again.
Then we passed above the clouds, and there was clear sky and sun outside the window, and the ride was completely smooth. The seat belt sign was turned off. Beverage service resumed. My parasympathetic nervous system kicked in, arresting the firing rate of the hyperactive neurons in my turbocharged amygdala, and I sank into a relieved, Dramamine-enhanced exhaustion. Half an hour or so later, we landed uneventfully in Washington.
But the Paxil had stopped working.
Not completely, at least not right away. But the illusion of being surrounded by an invincible anxiety-repelling Paxil force field had been dispelled. This, I now know, is not an infrequent occurrence. Certain SSRI medications can reduce anxiety and cut down on panic attacks—but according to the stress-diathesis model of panic, strong stimuli (like a turbulent flight) are potent enough to break through even medication-adjusted brain chemistry to produce intense anxiety. And this can be, because of the effect the breakthrough has on the thinking (or the “cognitions”) of the individual, like a magical spell being broken. (Other times, certain drugs just stop working without such stressful provocation; this phenomenon has been called “the Prozac poop-out.”)
After that day, my general anxiety level slowly rose again. My panic attacks began to recur—mild and infrequent at first, then more severe and more often. My flying phobia resurged—I needed to take a large dose of Xanax or Klonopin or Ativan before getting on any flight, and sometimes even that wasn’t enough. On my first airplane trip with Susanna, who was later to become my wife, my anxiety got so bad soon after takeoff that I began shaking and gasping frantically, and then, as Susanna looked on in bewilderment, my stomach cramped and I lost control of my bowels. I had planned the trip—three days in London—as a romantic vacation, an attempt to woo and impress her. This was not a good start. Nor was the rest of the trip much better: those parts of the vacation that I did not spend sedated into near catatonia by massive quantities of Xanax I spent quaking in mortal dread of the return flight.
I kept taking Paxil for several years, even after it had lost its panic-repelling magic, out of a combination of inertia and the fear of what might happen if I stopped. But by the spring of 2003, I had been on Paxil for six years, and my anxiety was once again in full bloom. It was time to try something new.
This is what prompted me to see Dr. Harvard, the psychopharmacologist. During my first visit, he was taking my case history when, as if to demonstrate my disorder, I had a florid panic attack that rendered me breathless and tearful, unable to continue. “Take your time,” Dr. Harvard said. “Continue when you’re ready.” Whether it was the facts of my case history or the vividness of the panic attack I unwillingly displayed for him, Dr. Harvard seemed surprised to learn that I had gone completely unmedicated for stretches of my life. He seemed amazed. To him, I was a hard case, not equipped for normal human functioning without pharmaceutical assistance.
We discussed the pharmacological options, eventually settling on Effexor, the trade name for venlaxafine, a serotonin-norepinephrine reuptake inhibitor (SNRI), which impedes the absorption—and therefore boosts the intrasynaptic levels of—both serotonin and norepinephrine in the brain. We talked about how to taper slowly off the Paxil, which I
did, carefully following his instructions, decreasing the dosage bit by tiny bit over a period of several weeks.
Over the years, I had from time to time considered trying to wean myself off psychiatric medication completely. After all, I reasoned, I’m pretty anxious on medication—how much worse can I be off of it? So once I finally did manage to taper most of the way off the Paxil, I thought, Why not, let’s try flying solo for a while—no more drugs. I stopped taking the Paxil and didn’t start the Effexor.
Here is what you don’t see in those TV and magazine advertisements for psychotropic drugs or even, with any real specificity or sympathetic understanding, in the clinical literature: the hell of going off them. I’ve never taken heroin, so I can’t say whether this is true (I suspect it isn’t), but many people claim that withdrawal from Paxil is as bad as withdrawal from heroin. The headaches. The exhaustion. The nausea and stomach cramps. The knee-buckling vertigo. The electric zapping sensation in your brain—a weird but common symptom. And, of course, the surge of anxiety: waking up at dawn every morning to a pounding heart and terrible dread; multiple panic attacks daily.
Despite my desire to try to “be myself” and function without pharmacological assistance for the first time in six years, I couldn’t hack it, and so one morning after barely a week off the Paxil, I took my first dose of Effexor. Within minutes, literally, I felt much better: the physical symptoms receded; my state of mind improved.
This cannot actually have been due to the Effexor’s therapeutic action—SSRIs and SNRIs generally need several weeks to build up in the synapses enough to start working. More likely, something in the Effexor somehow alleviated the effects of chemical withdrawal from Paxil. But what is cause and what is effect? Were the emotional anxiety and physical misery I felt after going off the Paxil really the effect of chemical withdrawal? Or was this simply what it feels like to be me undrugged? After all, I had been on psychiatric medication for long enough that maybe I had forgotten what it feels like to live in my naked brain.
Or was my misery that spring less the result of ill-fated drug-switching experiments than of the stress in my life? Two dates loomed at the end of that summer. The first was the deadline for the delivery of the manuscript of my first book, which by then had been in gestation for six years (roughly the length of time I’d been on Paxil) and had endured a harrowing journey—from editor to editor and publishing house to publishing house, through the descent into Alzheimer’s of my biography’s subject and the increasingly intrusive involvement of my subject’s powerful family—to get to this point. The other was my wife’s due date for the delivery of our first child.* Of the difficulties I endured that summer, it’s hard to know exactly which were a response to external stressors and which were drug related. And of those drug-related difficulties, it’s hard to know which were withdrawal effects from drugs I was weaning off and which were side effects from drugs I was going on.
The contrast between what the pharmaceutical industry’s promotional materials and the clinical research papers (many of them subsidized by grants from the pharmaceutical industry) say and what the roiling online communities of actual patients say is large. I believe both sides are generally honest and accurate as far as they go (the drugs can have measurable therapeutic benefits; the side effects and withdrawal symptoms can be awful), but neither one is wholly trustworthy. The drug companies, and the doctors subsidized by them, have a profit-motivated interest in pushing pills; the drug takers are pretty much by definition an unhappy and unstable bunch prone, like me, to being easily thrown by physical symptoms. Studies have shown that people who score high on scales of anxiety sensitivity tend to suffer drug side effects more severely. (A bunch of nonanxious people who took an SSRI would likely be much less bothered by any side effects and would therefore be less likely to complain about them in online forums.) So the antidrug rants of the pill-popping community cannot be taken at face value any more than can the assessment of side effects and withdrawal symptoms in the sometimes boosterish clinical literature.
Though the Effexor eased what seemed to be the physical symptoms of my withdrawal from Paxil, my anxiety and panic persisted—and then increased. When I told Dr. Harvard about this, his response, as the response of psychiatrists and psychopharmacologists so often tends to be, was, “We need to elevate your dosage.” The quantity of Effexor I was taking was not sufficient, he said, to correct the “chemical imbalance” in my serotonergic and noradrenergic systems. So I went from taking thirty-seven and a half milligrams to seventy-five milligrams of Effexor three times a day.
At which point my anxiety levels shot through the roof. At night, I would awaken in the grip of a raging panic attack. During the day, I was having multiple panic attacks—and even when I wasn’t having one, I felt as though I were about to. Never had I felt such chronic, persistent agitation; I couldn’t stop moving and twitching, couldn’t bear the feeling of being in my own skin. (The clinical term for this is “akathisia.”) Glimmerings of suicide began twinkling at the edge of my consciousness.
I called Dr. Harvard. “I can’t take it,” I told him. “I think maybe I need to get off the Effexor. I feel like I’m going crazy.” “You need to give it more time,” he said. And he gave me a prescription for Xanax, which he said would take the edge off my anxiety while giving the Effexor time to work.
Prescribing a benzodiazepine (like Xanax) to overcome the anxiety produced when a patient starts taking an antidepressant SSRI or SNRI (like Effexor) has been standard practice since the late 1990s. And in my case this worked—a little, for a short time. My anxiety receded somewhat, and the panic subsided, but only if I faithfully took my Xanax around the clock.
To work on my book, I had rented a decrepit office on the third floor of a crummy building in Boston’s North End, and to hasten my progress, I had hired a research assistant, Kathy, who shared the space with me. Kathy was an excellent researcher and, when I wasn’t feeling panicky, delightful company. But I was embarrassed about my anxiety and felt I had to hide it, which meant leaving when I felt panic coming on. So I was forever contriving errands to get me out of the office.†
Yet again I called Dr. Harvard. And yet again he said, “You’re not at a therapeutic level of the Effexor yet. Let’s increase the dosage.” So I started taking more Effexor, and a few days later my vision blurred and I couldn’t urinate. I called Dr. Harvard, and for once he sounded alarmed. “Maybe we’d better get you off the Effexor,” he said. But I’d been traumatized by the withdrawal symptoms I’d suffered when I’d stopped taking Paxil, and I told him so. (Discontinuation syndrome is now a clinically acknowledged Paxil phenomenon.) “I’m giving you a prescription for Celexa,” he said, using the brand name for citalopram, another SSRI. “Start taking it right away, and continue taking the Xanax.”
I did, and within a day my vision cleared and my urine again flowed, which would seem to suggest those problems had been side effects of the drug. But they might not have been: the tendency of anxiety sufferers to “somaticize”—to convert their neuroses into physical symptoms—means it’s possible my blurred vision and recalcitrant bladder were simply physical representations of my anxiety.
The transition from Effexor to Celexa was smoother than the transition from Paxil to Effexor had been, perhaps because I didn’t wean off one before going on the other. But since then, despite chronic and intermittently severe anxiety, I’ve not gone a day without taking an SSRI antidepressant, and I’ve not adjusted my dosage much, for fear of repeating the Paxil-to-Effexor experience. At times I think wistfully about my early days on Paxil, when I found a modicum of relief, and wonder if I shouldn’t switch back and try to achieve again that panic-free nirvana. But the clinical research is full of people who return to drugs they had taken earlier only to find them no longer effective.
And in any case, the experience of weaning off Paxil is not one I want to repeat.
Medication, medication, medication! What do I got to show for it?
—THE
SOPRANOS’ TONY SOPRANO TO DR. MELFI AFTER A YEAR ON PROZAC FOR HIS PANIC ATTACKS
Exploding into the national consciousness with the March 26, 1990, edition of Newsweek, whose cover featured a green-and-white capsule alongside the words “A Breakthrough Drug for Depression,” fluoxetine, under its trade name Prozac, would become the iconic antidepressant of the late twentieth century—a blockbuster for its manufacturer, Eli Lilly. The first selective serotonin reuptake inhibitor (SSRI) to be released in the United States, Prozac would before long surpass Xanax as the best-selling psychotropic drug in history—even as competing SSRIs (among them Zoloft, Paxil, Celexa, and Lexapro) would soon be on their way to outpacing Prozac.
With the possible exception of antibiotics, SSRIs are the most commercially successful class of prescription drugs in history. By 2002, according to one estimate, some twenty-five million Americans—more than 5 percent of all men and 11 percent of all women—were taking an SSRI antidepressant. The numbers have only grown since then—a 2007 estimate put the number of Americans on SSRIs at thirty-three million. These drugs dominate not only hospital psychiatry and our medicine cabinets but also our culture and natural environment. Books like Prozac Nation, Prozac Diary, and Listening to Prozac (and, of course, Talking Back to Prozac) populated the best-seller lists throughout the 1990s, and Prozac and Lexapro jokes remain a fixture of movies and New Yorker cartoons. Trace elements of Prozac, Paxil, Zoloft, and Celexa have been found in the ecosystems of American frogs (causing them developmental delays and anomalies), in the brains and livers of fish in North Texas, and in Lake Mead, America’s largest reservoir, which supplies drinking water to Las Vegas, Los Angeles, San Diego, and Phoenix.
Given how completely SSRIs have saturated our culture and our environment, you might be surprised to learn that Eli Lilly, which held the U.S. patent for fluoxetine, killed the drug in development seven times because of unconvincing test results. After examining tepid fluoxetine trial outcomes, as well as complaints about the drug’s side effects, German regulators in 1984 concluded, “Considering the benefit and the risk, we think this preparation totally unsuitable for the treatment of depression.” Early clinical trials of another SSRI, Paxil, were also failures.‡
My Age of Anxiety: Fear, Hope, Dread, and the Search for Peace of Mind Page 25