7

DRUGS

JIM MCGAUGH IS used to seeing his name on the sides of buildings, being feted, and seeing his portrait hanging in long hallways. But Jim McGaugh is no titan of industry, nor is he a star athlete or a financial wizard with a taste for philanthropy. Jim McGaugh is a neuroscientist. Into his eighties now, when he leaves his office at the University of California, Irvine’s Center for the Neurobiology of Learning and Memory (which he founded in 1981) on his way to the science library, he walks by James L. McGaugh Hall, a four-story lecture building completed in 2002. One of the first professors hired at UC Irvine when the campus opened in 1964 and a perennial Nobel favorite, McGaugh has devoted his entire sixty-year career to understanding the biological nuts and bolts of human memory.

An archetypal Man of Science, McGaugh looks a bit like a retired news anchor, a man who has lived inside the fort of his own gravitas for so long that it is hard to imagine that he was ever a gawky teenager, a boy with only a bike and a baseball glove to his name. Speaking in a kind of restrained stentorian tone that is reminiscent of the Midwest but is, in fact, native to the lost continent of pre-1970s California, McGaugh is strictly business. A mop of gray hair rises over the metal-framed glasses on his nose. Educated at Berkeley at the height of the Cold War, he works in a corner office overlooking the road that rings the campus. It’s an open space, the white walls continually washed in California sunlight; two broad desks are stationed in the corners. Access to the sanctuary is granted by a secretary whose mastery of his schedule and daily routine makes her seem less like an assistant than a third arm.

In the world of memory science, McGaugh is a living legend, having seemingly from day one dispensed with the timeworn idea that human memory is a static, frozen entity, a tape recorder forever running, seeing it instead as a living, inherently irrational, moody thing, a thing deeply prone to revision and manipulation.

If McGaugh’s work has a governing principle, it is this: unlike men, memories are not created equal. Early in his career, he saw that emotion, as much as any other factor, influences the way memories are formed in mammals. While this fact was not acknowledged by science until relatively recently, humans have intuited this for centuries. As McGaugh wrote in the preface to his book Memory and Emotion, “In medieval times, before writing was used to keep historical records, other means had to be found to maintain records of important events, such as the granting of land to a township, an important wedding or negotiations between powerful families. To accomplish this, a young child about seven years old was selected, instructed to observe the proceedings carefully, and then thrown into a river. In this way, it was said, the memory of the event would be impressed on the child and the record of the event maintained for the child’s lifetime.” This odd story of how fear can influence memory has come to dominate McGaugh’s work and will, in all likelihood, define his legacy.

Scientists have known for a long time that certain drugs enhance memory. One study published in 1917 by psychologist Karl Lashley showed that rats given very low doses of strychnine were able to memorize mazes much faster than rats given a dose of a saline solution. (In small amounts, strychnine, often used as a rat poison, acts as a stimulant.) McGaugh stumbled across Lashley’s research in the fifties when he was a graduate student at Berkeley and began thinking about what this might mean for the long-term storage of memory. He knew, for instance, that you could disrupt the learning process in rats by delivering an electrical shock about an hour after they had been trained in a laboratory task, a fact that suggested that something continued to happen inside a rat’s brain after a learning event occurred. Put another way, long-term memories are not made in an instant. It takes time for the “concrete” of memory to set. Neuroscientists refer to this process as “memory consolidation.” Keeping this in mind, McGaugh speculated that he might be able to enhance memory in rats by injecting them with a stimulant soon after learning a task, in essence throwing the rat into a river, as in his example from early Medieval history.

His graduate advisor thought it was a terrible idea when he brought it up to him. “It was a short discussion,” McGaugh wrote mordantly forty years later.

Frustrated by his advisor’s reaction, McGaugh waited for him to go on sabbatical in Europe and then began his experiment, injecting rats with strychnine shortly after training them. To his delight and astonishment, he discovered that his intuition had been right. Given a strategically timed dose of strychnine, rats made fewer errors and were able to navigate the mazes in the lab more efficiently. This idea that drugs administered after an event would enhance the memory of it has since been replicated in dozens of experiments throughout the world.

Soon after getting his PhD, McGaugh began experimenting using a number of other drugs to enhance memory, including amphetamines, picrotoxin, and morphine. After a series of dead ends in their work, McGaugh and Larry Cahill, one of his Irvine colleagues, began studying the effects of naturally occurring stimulants on memory. They soon discovered that adrenaline, the chemical released when a mammal is excited, enhanced the memory of a given event in a way similar to strychnine, and they could radically improve the ability of rats to remember experiences by injecting them with adrenaline.

But what if, McGaugh wondered, the reverse was true? What if you could inject rats (or people) with a substance that undermined the influence of adrenaline on the process of memory? What if you could make someone forget or at least dampen the power of a particular memory?

 

When I met McGaugh in his office on campus, he began by explaining the underlying neuroscience behind his work, concluding his minilecture with a blockbuster: there was a drug that could, from a neurological standpoint, prevent PTSD.

This drug—propranolol, a beta-blocker developed to prevent heart attacks in 1964—blocks the action of adrenaline within humans. As he explained, if you were to administer propranolol to a person a few hours after a traumatic event, you would block the neurological process that would otherwise cause that memory to become traumatic. In the language of neuroscience, you would prevent its “overconsolidation” within the brain and prevent the event from being permanently etched into the amygdala, one of the brain’s fear centers. You would prevent the patient from being “thrown into the river.” The experience would be remembered much like any other event was remembered—without the elevated heart rate, without the shortness of breath, and without the amygdala being unduly impacted. A serious car crash would be rendered identical to a trip to the coffee shop, neurologically speaking.

Further, he explained, propranolol was completely safe, could be taken orally, had few side effects, had been in wide use for decades, and was off-patent, which means that, like a number of older drugs (such as penicillin), it wasn’t controlled by a particular drug company.

The only catch was the timing. For propranolol to work, you had to administer it to the traumatized person within six hours of the “emotionally significant” event, and the sooner the better ideally. As I would learn later, the other not-small problem, at least for soldiers in a war zone or for refugees living in displaced persons camps and the like, is that for as long as the person is on propranolol, they are going to have to live without the benefit of adrenaline and the normal fight-or-flight response that would allow them to deal with danger. They would, in other words, be defenseless—tiger meat, from a Darwinian perspective.

An hour later, I left McGaugh’s office bewildered. While I’d gleaned a few nuggets of basic neuroscience, some things were far less clear to me than when I’d arrived. As I made my way across the sleek UCI campus, I wondered if I’d had it wrong all this time. All along, I had been thinking of trauma and PTSD as a profound, almost existential condition, a way of being in the world as much as a discrete diagnosis. Could trauma—the nightmares, the daemons, the vanished hopes, the impacted grief, the lost time, the great overturned jigsaw puzzle that used to be a person’s life—simply be the product of an ill-timed surge of adrenaline? An overrelease of epinephrine (the proper name for adrenaline) that resulted in a corresponding overrelease of norepinephrine (a neurotransmitter released during times of stress) in the amygdala? An overrelease that resulted in an overconsolidated memory trace in the fear center of the brain? Was this to be the historical conclusion to the odyssey begun by Lifton and Shatan four decades before?

The idea that our memories, the fund of information that makes us who we are, could be manipulated so easily flew in the face of nearly everything I wanted to believe about post-traumatic stress. It flew in the face of everything I wanted to believe about human nature. The world is so big, so complex, so replete with surprise and disillusionment and sublime loss, and the idea that they could all be banished by a heart pill invented six years before Lifton had even set foot inside the VVAW office was more than I was prepared to accept.

In my own way, I felt a little like John Keats in 1816, pondering the new world being ushered in by Isaac Newton. The natural sciences, he wrote,

 

. . . will clip an Angel’s wings,

Conquer all mysteries by rule and line,

Empty the haunted air, and gnomed mine—

Unweave a rainbow.

 

Nevertheless, there remained the not-insignificant problem of timing, of administering the propranolol within the requisite six-hour window after the traumatic event. As a lifelong student of war and disaster, I understood this to be a tall order indeed. The idea that you could expect to pull thousands of troops off the line during a war, or round up tens of thousands of hurricane victims, and administer them a drug that would render them helpless as sheep for ten to twelve days seemed like a classic case of science failing to live in the real world. In the case of infantry and special operations troops, you would in essence be rendering them combat-ineffective, denying them the use of the biological hardware fine-tuned over millions of years of evolution.

But, as I would learn after returning home and Googling around, researchers have been hard at work trying to solve the timing problem ever since McGaugh and Cahill made their initial discoveries. In 2008, Roger Pitman at Harvard, along with some of his colleagues, published a preliminary study in the Journal of Psychiatric Research that tackled the timing dilemma head on. While the number of research subjects involved was relatively small, the results were promising. Pitman took a group of patients diagnosed with PTSD, and after selectively exposing them to emotionally disturbing slide imagery, gave them doses of propranolol. What they found was astonishing: reactivating their memories with the slides coupled with the administration of propranolol reduced their symptoms by nearly 50 percent. (A similar experiment, conducted in 2001 by Pitman with McGaugh’s input, administered a ten-day course of propranolol to forty-one emergency room patients within six hours of a traumatic event, and it had a slightly better outcome.) Pitman’s results were encouraging enough that the Department of Defense awarded his team seven million dollars to develop a drug therapy to block this sort of traumatic memory reconsolidation in PTSD patients.

In January 2014, Pitman told me he was putting the final touches on a study that used “imaginals” similar to those used in PE therapy to activate patients’ symptoms several months after a traumatic event and treating them with propranolol, and that they’re finding the same pattern of reduced post-traumatic symptoms. In other words, the timing problem with propranolol may have been solved.

 

In Eternal Sunshine of the Spotless Mind, the 2004 film directed by Michel Gondry, a reclusive artist named Joel Barish (played by Jim Carrey) discovers that his exgirlfriend has had her memories of their relationship erased through an innovative procedure developed by a psychiatrist. Devastated and angry, Barish decides to have the same operation done to have his brain expunged of any trace of his ex. When he asks if there is any risk of brain damage, the psychiatrist, Dr. Mierzwiak, responds, “Well, technically speaking, the operation is brain damage, but it’s on par with a night of heavy drinking, nothing you’ll miss.” In time, Barish comes to regret his decision, and for the bulk of the film, we see the star-crossed lovers chasing one another through Barish’s various memories before they are vaporized by Mierzwiak and his technicians.

The film, written by Charlie Kaufman, hit theaters before propranolol’s medical potential had been widely reported (a 60 Minutes story on propranolol aired two years later, in November 2006), but the procedure depicted in the film resembles propranolol in enough respects that we have to credit Kaufman for creating a work of art that life has seen fit to imitate. In Kaufman’s story, the effect of this technologically induced amnesia is almost entirely negative, creating a kind of moral chaos. Characters, unconcerned about the consequences of their actions, actions that no one will remember, betray one another as a matter of course. The romance at the center of the film is nearly destroyed by the ability to erase memories on a whim. All sense of an objective, stable reality is lost. As the plot unfolds, we learn that the seemingly benevolent Dr. Mierzwiak has, in fact, used the procedure several times to delete an affair he’d had with his attractive young receptionist, played by Kirsten Dunst. The movie ends with Dunst’s character stealing all of Mierzwiak’s files and mailing them to his roster of patients in an effort to undo the damage wreaked by this neurological Frankenstein. Society, it seems, is not ready for wholesale memory erasure.

Kaufman’s screenplay, heavily influenced by the work of science fiction novelist Philip K. Dick, presages much of the criticism that has followed the advent of propranolol. In October 2003, before the most promising experiments by Pitman had even been published, President Bush’s Council on Bioethics released a lengthy monograph titled Beyond Therapy: Biotechnology and the Pursuit of Happiness, in which the authors, addressing the potential of propranolol, asked “Would dulling our memory of terrible things make us too comfortable with the world, unmoved by suffering, wrongdoing, or cruelty? Does not the experience of hard truths—of the unchosen, the inexplicable, the tragic—remind us that we can never be fully at home in the world, especially if we are to take seriously the reality of human evil? Further, by blunting our experience and awareness of shameful, fearful, and hateful things, might we not also risk deadening our response to what is admirable, inspiring, and lovable?”

The Council’s report, which was regrettably loaded with early War on Terror–style references to “evil” and “evildoers,” still manages to get its basic point across: propranolol is one of the most morally challenging drugs to emerge in a very long time and could radically alter how society deals with trauma and moral terror. As numerous bioethicists have observed, the moral problems it introduces are virtually limitless. As Chuck Klosterman, an author and Esquire columnist, argued, “Propranolol might be the most philosophically vexing pharmaceutical since Prozac. It openly questions the significance of reality.”

Klosterman, an avid student of pop culture, goes on to ask, “How big is your life? That is neither a rhetorical nor impossible question. The answer is easy: your life is as big as your memory. Forgotten actions still have an impact on other people, but they don’t have an impact on you; this is the entire point of Memento. Reality is defined by what we know, and we (obviously) can’t know what we can’t remember. What this means is that propranolol provides an opportunity to shrink reality. It doesn’t make past events wholly disappear from the mind, but it warps their meaning and context. So if people’s personalities are simply the aggregation of their realities (and if reality is just an aggregation of memories), it can be argued that propranolol is a drug that makes people’s lives artificially smaller.”

Klosterman and other critics assert that by tinkering with the rudiments of human memory, we might unwittingly change human nature itself, rendering terror, atrocity, rape, and every manner of depredation a banal occurrence. As Paul Outka, an English professor at Florida State University, inveighs, “To be denied a ‘normal psychopathology,’ to be remade into an entity that can witness any horror and survive without permanent damage, is to be a fundamentally different sort of human.”

Outka makes a good point. While it is too early to say exactly how powerful propranolol will be in diluting the power of traumatic memories, one of the foundational principles of recognizing trauma among humans is that it serves a greater moral purpose. PTSD is, in a manner of speaking, a way of institutionalizing moral outrage. As Robert Lifton and others have argued, to treat trauma on a strictly technical basis, like any other psychic ailment, is to miss the point entirely. To them, trauma transcends the individual. Trauma is symbolic. Trauma is history made manifest in the flesh. Trauma, when heard by society, is a form of testimony.

It is no coincidence that since the Vietnam War and the advent of PTSD, the casualty totals of American wars have fallen dramatically. Among the many things that PTSD has done is given victims of violence a status they lacked before. Society today is far more sensitive to the concerns of the victimized than it was in the first half of the twentieth century, and this is, in no small measure, due to the advocacy work of the Vietnam generation. If through the miracles of modern neuroscience we end up significantly diluting the moral force of trauma, we risk creating a far more violent and cruel society than the one we currently live in.

Nevertheless, not everyone is convinced that propranolol represents a threat to the social order. Adam Kolber, a law professor at the University of San Diego and the author of a widely read neuroethics blog, has, with respect to propranolol, advocated for what he calls “freedom of memory.” Kolber quotes one survivor, who said, “I have severe [PTSD] and would sell my soul to the devil himself to be rid of my 24/7 hellish flashbacks and night terrors.” His extensive sixty-six-page legal review of the possible impacts of propranolol concludes by saying, “Concerns over memory dampening are insufficient to justify broad restrictions on the therapy. Furthermore, having the choice to dampen memories supports our interests in self-determination and in avoiding mental illness and upset enables us to identify more strongly with memories that we decide to keep. Given the potential that memory dampening has to ease the pain of so many people, and that, at a minimum, memory dampening ought not be entirely prohibited, it follows that we should have some right to dampen our memories.”

Despite the controversy surrounding its use, the therapeutic potential of propranolol and beta-blockers is still largely unknown. The drug, in its current form, can diminish the potency of certain types of memories under certain conditions, but it is by no means a memory wipe–type drug of the sort depicted in science fiction movies like Men in Black. As Pitman has argued, “The original memory is indeed still there, deep inside the brain.” And as I discovered firsthand undergoing imaginal therapy with the VA, post-traumatic stress is frequently caused by a whole series of stressful events, a large swath of time spent under stress, rather than a single, discrete event that can be easily isolated and treated with beta-blockers.

In this way, propranolol raises still more vexing issues with respect to the PTSD diagnosis as a whole because in no clinical trial have post-traumatic stress symptoms been eliminated completely by administering either a beta-blocker or another similar drug. Virtually every experiment published so far shows that disrupting memory consolidation and/or reconsolidation results in the PTSD rate being cut roughly in half. What then are we to make of this other half, the patients who despite being given propranolol or a similar drug go on to develop post-traumatic symptoms? Are they the result of a flawed experimental design? Are they noncompliant patients? Are they misrepresenting their symptoms to the assessors who give them the CAPS? Or is it possible that part of what we call PTSD exists outside of the realm of neuroscience as it is understood today? Is it possible that some aspect of trauma exists in the moral sphere, a sense not merely of being haunted by horror but in some way feeling tainted by it?

Regardless of the technical specifics, the dearth of knowledge about the long-term consequences of mixing beta-blockers and trauma remains a serious concern. Although millions of people have taken propranolol over the years, only a relative few have taken it in the manner being advocated by scientists. And tinkering with the human nervous system and the fight-or-flight response, which has kept humans alive on earth for millions of years, is not without risk. The heightened perception of danger and the exaggerated startle response we see in post-traumatic stress is something that evolution has preserved and has undoubtedly helped to keep humans biologically competitive for millennia. As with so many things in science, we have only the slightest idea of what will happen after a new technology is introduced into society. The problem, really, is that while humanity continues to experience huge leaps in technology, we experience no equivalent leaps in our ethical capacity. In the never-ending arms race between technology and ethics, technology always wins. Researchers who tally the results of this immortal race have a name for it: history.

As I’ve argued elsewhere in this book, technology is the great transformer of trauma. With the advent of propranolol and our ability to manipulate memory to an unprecedented degree, we will likely see a radically different set of human responses to trauma in the years to come. Because propranolol was approved by the FDA decades ago, it is already being prescribed on an off-label basis in emergency rooms and by psychiatrists across the United States, with some success from what I’ve been told.

Interestingly, the researchers most closely associated with this new procedure have been largely silent on its potential ethical implications. I asked both Pitman and McGaugh about the potential negative social impacts of propranolol, and both declined to respond.

 

Thankfully, there are a number of other drugs useful for treating post-traumatic stress that are less controversial than propranolol. Prazosin, a drug first used to reduce high blood pressure, has been found to be effective in reducing nightmares in traumatized people, and knowledge of its properties predates the advent of PTSD. Prazosin works by limiting the action of noradrenaline in a part of the brain known as the locus coeruleus, an area heavily associated with arousal and wakefulness. Prazosin doesn’t knock you out. It’s not a sedative. It extends sleep once you doze off, and its effects last around eight hours. One 2003 study conducted by Murray Raskin on ten Vietnam veterans found that taking a small dose of Prazosin before bedtime dramatically reduced their nightmares and other sleep disturbances. A subsequent study using civilian PTSD patients found that subjects slept on average ninety-four minutes longer than those who were not taking the drug. Many of those who take Prazosin describe their traumatic, often repetitive nightmares being replaced by regular dreams devoid of traumatic content.

Some of the most experienced psychiatrists who treat PTSD believe that quality, restful sleep is the sine qua non of PTSD recovery and that its absence serves to exacerbate other symptoms of anger, impulse control, and general irritability. So Prazosin holds tremendous potential, and it is unusual among PTSD drugs in that it directly addresses one of PTSD’s core symptoms. Some clinicians have even noticed that their patients drink less while on Prazosin because they’re not using alcohol to help them get to sleep or as a means to escape from the pain of their symptoms.

The most popular class of drugs prescribed for PTSD are the Selective Serotonin Reuptake Inhibitors, or SSRIs, which bring about higher levels of serotonin in the brain. Prozac, Zoloft, Paxil, and Celexa are all SSRIs. One 2004 survey that looked at 220,000 VA patients found that SSRIs were far and away the most prescribed drugs for PTSD; 85 percent of those studied, if they were on psychotropic medication, were on an SSRI. (Given the VA’s leadership role in PTSD research, it is likely that this pattern holds true for the general population.) Among the SSRIs, Zoloft is the most commonly prescribed for PTSD. SSRIs do not address the underlying pathology of PTSD, but they do help patients manage their symptoms.

Jenny G., an air force veteran who saw combat in one of the deadliest provinces in Iraq, began taking Zoloft for her PTSD after Prolonged Exposure therapy brought her nightmares back, and she told me, “Medication has really changed my life. Before I went on meds I would obsessively remember and worry about the littlest things. On Zoloft, I don’t worry as much. I don’t obsess as much. I’m less angry. I got to a point where I would not be able to eat or sleep because I would be worrying about something, and it would make me sick. At one point, my ex-husband threatened to take custody of my daughter. That was probably my breaking point. My doctor told me, ‘I’m afraid you might have a stroke or something.’ So I went on Zoloft. I couldn’t fly anymore after that because I was on meds, but it was worth it.”

Once out of the air force, Jenny briefly went off Zoloft in order to take part in a VA study with another drug and found that her symptoms reappeared almost immediately. “I went right back to the way I was before. I was in such bad shape. If I hadn’t gone back on Zoloft I think I probably would have been arrested for assaulting someone. My personal hell is Walmart. There are just so many people in there, people all over the place. People just get right up next to you, no matter where you go. Unmedicated, I would just go crazy if I had to go in there and end up having huge inner arguments with myself. For some other veterans I’ve talked to, Zoloft hasn’t worked at all. But it’s been a miracle for me. It seems to work with my brain chemistry. It has definitely brought back a little bit of who I used to be. I still feel like an alien, not the old pre-Iraq version of me, but it’s better than before.”

Zoloft and other SSRIs have a decent track record with PTSD, but their use with the disorder is essentially accidental, as SSRIs were originally designed to treat depression, not PTSD. Shortly after Prozac, the first SSRI, was marketed in 1987, VA psychiatrists, hearing about the great successes their colleagues were having with it, began prescribing it for PTSD patients, even though the research didn’t yet exist to support its effectiveness with the condition. While the results of SSRIs on PTSD patients were positive, they have never been on the order of the transformative, revolutionary changes seen in some depressives, changes that came to dominate the American imagination in the mid-1990s with widespread reports of Prozac’s ability to make some people “better than well.” Instead, what doctors found was that SSRIs relieved some of the depression and anger associated with PTSD and alleviated the suffering of the most anxiety-ridden sufferers, like Jenny G. That Prozac, Zoloft, and Paxil are all considered by most physicians to be safe drugs, easy to prescribe, and with a very limited side-effect profile has made this development easy to accept, especially when they are compared to some antipsychotics, like Seroquel, which have proven to be controversial. As one scientist at Eli Lilly put it, “Prozac is a very forgiving drug.”

One widely held belief among psychiatrists is that mental health disorders are best treated with a combination of medication and psychotherapy, and this seemed to be the case with PTSD, but by the end of the twentieth century, there was no still no science to support giving SSRIs to PTSD patients. They certainly didn’t seem to be hurting patients, and they helped lift them out of the deep funks and ruminative purgatories that so many trauma survivors are prone to. But it wasn’t until 2002, some fifteen years after Prozac’s introduction, that the results of the first two randomized clinical trials on Zoloft as a treatment for PTSD patients were published.

These studies mostly confirmed what practitioners in the field had been seeing for years. Both experiments saw modest improvements in CAPS scores for hyperarousal and emotional numbing, but the drugs did virtually nothing to reduce the flashbacks and nightmares that are the hallmark of PTSD. The other major problem that the clinical trials revealed was that while Zoloft had a marked effect on civilian women who had been sexually traumatized, it had virtually no effect on a group of male Vietnam veterans recruited for a series of studies. (Since 2002, other studies have been published on non-American veterans using SSRIs with slightly improved results.) SSRIs seem to perform best on certain types of PTSD patients, with female victims of sexual assault being the most responsive to medication. Additionally, there is almost no evidence that those suffering from PTSD caused by single, onetime events, like car crashes, natural disasters, and terrorist attacks, benefit from SSRIs.

Despite these shortcomings, the trials published in 2002 and others were enough to persuade the Food and Drug Administration to approve Zoloft and Paxil for treating PTSD. In 2004, the American Psychiatric Association followed suit, recommending SSRIs for the treatment of PTSD with “substantial clinical confidence.” There was now a curious duality to drug therapies and PTSD. On the one hand, there was a class of drugs that were safe, popular (both among doctors and in the public mind), and seemed to address a few of the major symptoms associated with PTSD. On the other hand, none of the clinical trials on long-term chronic Vietnam veteran PTSD sufferers, a group that had long served as the nucleus for PTSD studies, had shown an improvement in symptoms. Indeed, in one study using Vietnam veterans, the placebo group outperformed the group given SSRIs. Seeming to recognize these inconsistencies, in 2008 the Institute of Medicine, the most prestigious medical practice review body in the United States, released a report that officially recognized what many researchers already knew: there was no evidence that any drug actually treated PTSD across the board, SSRIs included. In the lexicon of the VA, there remains no “gold standard” pharmacotherapy for PTSD, and in the VA’s clinical literature, the various pharmacotherapies are described as merely “an important adjunct to the evidence-based psychotherapies for PTSD.” This lack of drug success no doubt played a role in the VA’s decision to support the broad rollout of Prolonged Exposure and Cognitive Processing Therapy beginning in 2006.

One of the major roadblocks to substantial drug breakthroughs with PTSD is that unlike ailments such as clinical depression and attention deficit disorder, PTSD has never garnered the attention of the pharmaceutical industry, which traditionally underwrites the lion’s share of drug research. As Dewleen Baker, one of the investigators on the original 2002 Zoloft clinical trial, explained, “PTSD was defined much later than depression and most drug companies go after depression first, then only develop drugs for PTSD as an afterthought. Many within the industry don’t understand the relatively high prevalence of PTSD, and I think some have been scared off by the crazy Vietnam veteran myths. Sertraline [Zoloft] was studied in part because the research was driven by someone who had a relative with PTSD, a Korean War veteran, and knew about the disorder and the need for treatments. Companies only make money if they study and get drugs to market which can be patented, thus potentially non-patentable compounds are not in contention.”

This frustrating lack of progress with drug research also reveals one of the lingering problems with PTSD: the utter lack of a coherent neurobiological model.^* Simply put, neuroscientists, despite their claims to the contrary, have only the most rudimentary knowledge of what’s going on inside the brain of a traumatized person. The PTSD diagnosis, from its earliest days, was criticized as being too nebulous, too heterogeneous, too diverse in etiology, too full of gauzy philosophical ideas to earn a clear position within the psychiatric nosology. Many of these criticisms, evident to researchers in the late 1970s, remain unresolved forty years later. Powerful treatments for mental health disorders arise from a deep understanding of the causes of those disorders. Identifying the altered adrenergic mechanisms seen in PTSD is only the first step toward that understanding. Unfortunately, it’s questionable whether that step will be taken; as off-patent drugs, there is little economic incentive to research and market either propranolol or Prazosin. To mount a successful treatment campaign against PTSD, you don’t just have to know what it is and where it comes from, you have to understand what it does, an understanding that is so far lacking.

To be fair, researchers don’t completely understand why SSRIs work for depression either, but depression is a much older and more common ailment than PTSD, and the major pharmaceutical companies have had far more time and financial incentive to develop drugs to treat it. The development of Prozac, for instance, reaches all the way back to the 1960s, when a handful of organic chemists working for Eli Lilly began thinking about the role of serotonin in the brain. Matthew Friedman, the first and longest-serving executive director of the National Center for PTSD, has even suggested that in the future a radical “paradigm shift” for PTSD might be in order, whereby the diagnosis is sliced up and reconceptualized as a cluster of related disorders, in which “several distinct, pathological posttraumatic disorders are operationalized.” In Friedman’s view, this could mean dividing it into a group of disorders based upon how it alters the adrenergic mechanism, the glutamatergic mechanism, the hippocampal-pituitary axis, and so on.

As a society, we now find ourselves at a curious crossroads with PTSD. The disorder has never been closer to the center of the national conversation, and yet its relationship to pharmacology remains as uncertain as ever. Unlike depression, which has long been recognized as a fundamental part of the human condition, PTSD remains to a surprising degree a cultural and existential phenomenon, a condition with no cure and little solid biological grounding. What does this mean for its future as a vein of human experience? As a diagnostic category? Given our current love of pharmaceuticals, the fact that PTSD isn’t powerfully treatable with any class of drugs would almost seem to doom it from a medical perspective, and yet the diagnosis has continued to grow in popularity, a situation that raises several thorny questions: If our biological grasp of PTSD is so weak, if it can’t be effectively treated with drugs, then what sort of disorder is it exactly? Can something exist as a psychiatric disorder if no dedicated drugs exist to treat it? Is it truly a psychiatric disorder, as we understand them today, or is it perhaps something akin to a “moral injury,” as some theorists, like Jonanthan Shay and Brett Litz, have suggested?

My own view of the relationship between drugs and PTSD is reminiscent of what Frank Sinatra said when a reporter asked him about his philosophy of life—“Basically, I’m for anything that gets you through the night—be it prayer, tranquilizers, or a bottle of Jack Daniel’s.” I think you should judge pharmaceuticals based on how useful they are to you and balance their side effects with how you want to live your life. (I personally think that alcohol, taken in moderation, is one of the best PTSD drugs ever invented, a view held by several other trauma survivors I know.) Modern pharmaceuticals raise a host of vexing philosophical questions about human agency and identity, but with respect to PTSD, I am inclined to say that if a particular drug works for you and helps you control your symptoms, helps get you through the night, then that is almost certainly a good thing.

I have never taken Zoloft or any other SSRI (although I nearly did as part of a VA experiment), but I understand that in many cases, Zoloft and other similar drugs have been one of the only things that have kept some trauma survivors from killing themselves. PTSD represents so many things to so many people, is so closely tied to our complex cultural narratives about death and aftermath, and is so off-putting to Big Pharma that I think it’s unlikely (with the possible exception of propranolol) that a defining drug will emerge any time soon.