The Evil Hours (35 page)

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?