The End of the Nightmare
When a local VA doctor discovered that a decades-old generic drug relieves the traumatic nightmares of PTSD, it took 20 years and thousands of sleepless nights to gain acceptance.
Every morning at 3:15, Johnny Banks walks the perimeter of the Westfield Southcenter Mall. It is his daily exercise and it takes him 30 minutes. He likes to take his walk at that hour because, he says, he’s an early riser and he doesn’t like crowds.
Every evening, Banks, 64, goes to bed at 7:30, wakes at 11pm, watches TV and maybe dozes a bit more, then gets up again at about 2:15am. It may be an unusual schedule, but if he sleeps longer, he feels too groggy. And he is grateful every day for the sleep he gets, because for more than 30 years, he couldn’t sleep more than two hours a night.
Banks was 18 when he went to Vietnam in December 1967. The sleepless decades began when he came home one year later. He was nervous. He had nightmares, full of the smells of white phosphorus and burning bodies. Sometimes he dreamed he’d been shot in the head. Through the next three decades, he married, divorced, married again, and worked to support his six children. But he always had a hard time holding down a job. Banks estimates he’s had 40 or 50 different jobs in his life, in shipyards, sheet metal factories, longshore warehouses. It’s hard to keep an even keel on two hours of sleep a night.
If you met Banks today, your eyes would be drawn to his red baseball cap, emblazoned with the words: “African American Veterans Group of Washington State.” Banks jokes that he has “two of these caps for every day of the week.” The group, founded by the late and much-loved Lemanuel Jones, began as a lifeline of support for Vietnam veterans and has since grown to include veterans of earlier and later wars: World War II, the Korean War, the Gulf War and the wars in Iraq and Afghanistan.
In late 1994, the Veterans Affairs Puget Sound Health Care System, then known as the Seattle VA Medical Center, formally acknowledged the African American Vets group’s valuable work and assigned them an official adviser, its new chief of psychiatry, Dr. Murray Raskind, who at the time was known mainly for his research on Alzheimer’s disease.
Raskind’s affiliation with the group never would have happened if the VA hadn’t found space for the Alzheimer’s Disease Research Center. “Of course,” Raskind says drily, “there are a lot of white Jewish leaders of black vets groups throughout the country! At first I was seen as a spy for the Establishment.” But that opinion gradually subsided, and Raskind has led group therapy for those veterans on Wednesday evenings ever since.
By the time Raskind began meeting with the African American vets, the symptoms that plagued most of them had acquired a name: posttraumatic stress disorder. Raskind, with his Alzheimer’s background, likes to remark that he specializes in “people who can’t remember and people who can’t forget.” But in the mid-1990s, this wasn’t very funny and he knew it. The Vietnam veterans he saw every Wednesday had been trying—and failing—to forget their own war horrors for so long that many of them were not just worn out but suicidal. Most were drinking heavily. Alcohol was the only drug that would reliably put them to sleep. Unfortunately it didn’t keep them from being jolted awake by combat nightmares.
That first year, Raskind recalled, “It became clear to me that as they taught me about, one, PTSD and, two, growing up black in America, their main point was, ‘Doc, I just can’t sleep.’ And it wasn’t so much getting to sleep that was the problem; it was, once you got to sleep, you were back in a trauma nightmare, which woke you up sweaty, anxious, having to check for threats in the environment. They described it as an adrenaline storm.”
An adrenaline storm. As in, a tidal wave of that fight-or-flight response we’re all wired to feel when confronted with a sudden danger, like an approaching grizzly bear or a performance review we know is not going to go well. Not something that anyone would want to wake up to in the middle of the night, every night.
Raskind’s Alzheimer’s research had been focused on the brain’s adrenaline system. “Or more technically, what the brain’s norepinephrine system was doing in Alzheimer’s disease and it struck me that it should be perhaps explored in PTSD as well.” Norepinephrine, a sort of partner to adrenaline, makes us feel instantly more aware and focused when danger is present. As Raskind puts it, “the brain’s norepinephrine system’s job is to make you alert to novel stimuli in the environment. Of course when you’re in a combat situation, that’s number one—to keep you and your buddies alive—especially in wars like Vietnam, Iraq, and Afghanistan, “when ambush, whether it’s by people or IEDs, is the major combat situation.”
The problem, Raskind explains, is that, though it is useful to have your norepinephrine and adrenaline systems at a high pitch of sensitivity when you’re in combat, turning it all off is very difficult. What the vets were telling him is that, especially at night when they desperately needed rest, their norepinephrine stayed responsive.
Raskind was particularly troubled by one veteran who was actively suicidal after reliving, night after night, the killing of his best friend at the height of the Tet Offensive, a death caused not by enemy fire but by the accidental discharge of the suicidal veteran’s own M16.
Raskind grew up in Queens and White Plains, earned his BA from Brown University, and graduated in 1968 from Columbia University College of Physicians and Surgeons. He spent two years as an intern and then a resident in internal medicine at Harlem Hospital Center before moving to Seattle in 1970 to complete a three-year residency in psychiatry at the University of Washington School of Medicine.
As he pondered the notion of such nightmares being triggered by an adrenaline storm, Raskind, who is now 71, found himself thinking of drugs that had been introduced to combat high blood pressure when he was a very young doctor in New York. In the mid-1990s those then-more-than-20-year-old drugs lowered blood pressure by blocking the effects of norepinephrine in the brain. There are only two receptors for norepinephrine in the brain: the beta receptor and the alpha-1 receptor and Raskind knew that one of those drugs, propranolol, helped people with public speaking anxiety or musicians with performance anxiety by blocking the beta receptor.
So he gave the vet who worried him the most a trial dose. A week later, the vet came back and said, “Doc, we’re going the wrong direction, my nightmares are even worse.”
“I looked in the Physician’s Desk Reference quickly—back when we used to have books—and I looked at the side effects of propranolol, and the fifth one was, ‘intensifies dreams,’ which was news to me! But from my work in Alzheimer’s, [I knew] there were two receptors for norepinephrine, and they had opposite effects on some brain systems. So I thought, Gee, it’s a long shot, but if propranolol makes the nightmares worse, maybe if we can find something that blocks the alpha-1, it’ll have the opposite effect and make the nightmares better, which would be a good thing.”
So Raskind went back to the 2,500-page Physician’s Desk Reference and found one—and only one—alpha-1 blocker of norepinephrine: a drug called prazosin. It was first marketed as Minipress for hypertension by Pfizer in the 1970s, and is now a cheap, generic medication whose patent has long ago expired. He cross-checked other pharmacological manuals to confirm that it crossed the blood-brain barrier. It did.
He convinced the vet to try a gradual dose of prazosin, slowly increasing it to five milligrams. After three weeks, said Raskind, the vet “gets up in group and shakes my hand and says, ‘It’s the first night I’ve slept since the Nam.’ ” This was a man who had been taking five different medications and drinking a fifth and a half of vodka a night simply to put himself to sleep for a few hours. “Gee,” Raskind added, “I didn’t realize I was such a good psychotherapist! Because this had to be a placebo effect.”
Still, Raskind decided to try prazosin with a second vet from the African American Vets Group, a survivor of the 1968 siege of Khe Sanh. He described nightly horrors as vivid as a videotape implanted in his head, in which North Vietnamese soldiers were surging out of tunnels, and it was his fault because he had placed the Claymore antipersonnel mines in the wrong direction and he and his buddies were about to be overrun. This second veteran, who had become so irritable from lack of sleep that his workmates at the Boeing 767 Everett plant had built “a little hootch for him to keep him away from everybody,” reported equally stunning results. He began sleeping soundly for the first time in 30 years.
Raskind was excited. He decided to conduct a placebo-controlled study. But because prazosin was off patent—meaning cheap, generic; meaning there was no money to be made—no pharmaceutical manufacturer was willing to back a drug trial. Many grant reviewers were skeptical too: Why this sudden interest in an off-label use of a very old drug? Three times, Raskind’s applications for grant funding were rejected. Finally in 2000 he scraped together enough money to run a modest study, which he was only able to undertake because he had the staff in his VA department, known as the Northwest MIRECC—Mental Illness Research, Education, and Clinical Center—to do it.
Johnny Banks was his first volunteer. For the first three months, he was given a placebo. The burning-body nightmares didn’t stop. But then he was switched to prazosin, and suddenly, Banks reported, “180-degree turnaround.” In the 13 years since that trial, he says he has never missed a single day of taking his pills. Before prazosin, nightmares tormented him at least four to six times a week, sometimes twice a night. Since then—next to none.
For Banks, prazosin came too late to calm the troubled waters of his work life, but it has made for a far mellower retirement than he might have had otherwise.
For Raskind, the study began a long effort to get the Department of Defense and the VA to pay attention to prazosin. “The VA’s just a conservative organization,” Raskind said. But the larger, “more interesting problem” is the way the Federal Drug Administration approves drugs. “No generic drug will ever be FDA-approved for anything,” Raskind explained, “because the FDA approval process only applies to new, still-under-patent drugs that the pharmacological company is willing to invest in very large, multisite clinical trials to generate the data necessary to present to the FDA for an up or down decision.”
In fact, says Raskind, the FDA has approved only two drugs for PTSD: the antidepressant selective serotonin reuptake inhibitors, or SSRIs, known as Zoloft (generic name: sertraline) and Paxil (paroxetine). “The only reason they’re approved is that back around the turn of the millennium they were still under patent, and the companies that held the patent decided they were going to spend $100 million to see if they could get a label indication from the FDA for PTSD.” Consequently, most drugs prescribed for PTSD—Trazedone and Ambien for sleep and other SSRIs like Prozac or other antidepressants—are prescribed off label.
On the one hand, this was good news. Doctors could try drugs designed for other uses to see if they might relieve PTSD symptoms. On the other hand, when an inexpensive, generic drug prescribed off label worked—like prazosin—the only way people learned of it was via word-of-mouth. “You’ll never see a TV ad for prazosin,” said Raskind.
In the early 2000s, Raskind, Banks, some of the other African American vets and their successes with prazosin were featured in the local papers. What is striking is how little the wars in Iraq and Afghanistan are mentioned: none in the Seattle P-I’s story, which ran September 9, 2002, during the buildup to invasion, and only a vague, general reference to the “new generation of soldiers returning from Iraq” in the Seattle Times story, which ran December 29, 2003, when the wars were well under way.
As those wars ramped up over the next few years, more and more young PTSD patients were referred to Raskind and Dr. Elaine R. Peskind, his partner in both Alzheimer’s and PTSD research. The two of them began a hectic decade of shuttling back and forth between the VA in Seattle and Joint Base Lewis-McChord south of Tacoma. The crush of their patient loads made it even more difficult to spread the word about prazosin, especially without support from the pharmaceutical industry or the VA, which was, before 2010, notoriously reluctant to confer diagnoses of PTSD. (After a number of scandals in 2008 and 2009 involving VA physicians being arm-twisted into changing PTSD diagnoses, which can confer expensive lifetime benefits, to diagnoses like “personality disorder” connoting a preexisting condition for which the VA would not have to pay, the rules requiring veterans to document the specific traumas that triggered symptoms were dropped in 2010. Now veterans are required only to show that they served in a war zone and had duties that could have led to the crisis that caused their PTSD.)
The doctors realized they needed to do some educating about the importance of sleep and the difference between normal, restorative dreaming—including ordinary stress dreams—and PTSD-induced nightmares, which not only serve no restorative purpose but are psychologically harmful.
Dr. Peskind explains it this way: “We have what are called sleep epics and sleep cycles. A sleep cycle takes about 90 minutes: light, deeper, really deep, dreaming sleep. Your first episode of dreaming sleep will happen after about 90 minutes. Then, over the course of the night, the deep sleep becomes shorter in duration and the dreaming sleep longer. So that by the early morning hours, you have most of your dreaming sleep. I think everybody has had the experience of waking up in the middle of the dream in the early morning hours; those are the dreams you remember. They’re very different from trauma nightmares.
“Trauma nightmares are like videotapes. They are exact re-experiencing of the trauma as it happened. They don’t have fantastical elements. They are literal, visual, and they’re exactly like the trauma experience. And they don’t have the function of normal dreams. It’s thought that normal dreams actually are beneficial and part of your brain’s ability to process what happened to you during the day and during the past, and to incorporate them in a constructive way into your life. Trauma nightmares are not like that. You’re having that experience over again. Your brain doesn’t know it’s not real. It’s real, as far as your brain is concerned. So they are in fact retraumatizing.”
“Vets often wake up in a sweat with their heart pounding and their bed clothes torn up. They’ll often strike their bed partner, without really being aware of it—and normally, during dreaming sleep, you should be paralyzed, you should have sleep paralysis. They’ll get up, patrol the perimeter, check all the doors, make sure they’re locked, peer through the blinds, make sure no one’s out there. They’ll get up and watch TV or do something else. So it’s really very different from normal dreaming sleep. It’s an interruption of the normal dreaming process, not normal dreaming. And it doesn’t serve that restorative function that normal dreaming does.”
During the 2000s, the prazosin success stories began to spread from the VA to Joint Base Lewis-McChord (JBLM). In 2006, Colonel Kris Peterson, chief of psychiatry at the Madigan Army Medical Center, agreed to team up with Raskind and Peskind to plan a five-year project they called the Nightmare Reduction Initiative, which would include placebo-controlled trials of prazosin in active-duty soldiers.
Tammy Williams, a JBLM social worker, was assigned to recruit candidates. In addition to reaching out to doctors at Madigan, she talked to brigade leaders and hung a banner outside the Madigan entrance, with the words “Got nightmares?” in large print and a phone number to call. Nearly 400 soldiers responded. Over the next five years, 67 of them, all suffering from combat trauma nightmares and other symptoms of PTSD, were randomly selected and assigned to treatment with prazosin or a placebo for 15 weeks.
Since then, Bell has suffered from substantial chronic pain in addition to PTSD. He still sometimes walks with a cane. He was given a 100 percent disabled discharge from the military. But before he was discharged, he heard about the “sleep study.” His wife urged him to make the call. Bell had been having the same combat nightmare at least twice a week, one so gruesome he could not bring himself to describe it.One participant was Sergeant Major Robert Bell. Now retired, after 28 years in the army, Bell was deployed in the 1990 Gulf War and has been stationed in Germany, Korea, Colorado, and Texas. In 2005, his unit volunteered to go to Iraq. “I got blown up twice,” Bell said. The second time, for which Bell was decorated with a purple heart, was worse. “I was in the wrong place at the right time,” Bell explained. He was the gunner in a Humvee, standing up, when the vehicle was struck by a three-array IED. He was hit in the back, forearm, and left shoulder; 13 pieces of shrapnel lodged in his back, and he credits armor plating with saving his arms. Bell also suffered a traumatic brain injury. His ears rang for two days.
Once the dose was properly adjusted, Bell responded to prazosin.
“I couldn’t tell you the last time I had a nightmare or a day tremor,” he said.
Lieutenant Colonel Jeffrey Hill, deputy chief of Madigan’s Department of Behavioral Health, supervised the study in 2011, its final year. Hill, a career army psychiatrist, was moved by the number of soldiers suffering from combat-PTSD nightmares who said they were “doing this for their buddies,” even if it meant being assigned a placebo instead of the drug that might end their own nightmares; even though, without sleep, humans can become psychotic or at the very least grumpy and hard to live with, which can have a huge ripple effect on spouses and children.
While acknowledging that the military has a history of attaching stigma to PTSD diagnoses, Hill maintains that the higher command levels are now “very pro mental health” treatment. They have seen the price their troops have paid when PTSD goes untreated: in compromised job focus, jeopardized safety, career stagnation, and family problems. That’s why Hill found it so satisfying to work on the prazosin study. “To be able to see people get better is great,” Hill said. “Sleep is a big part of treatment. Other symptoms all get better with sleep.”
This belief in the power of sleep is now an official cornerstone of army health policy. In September 2012, U.S. Army Surgeon General Patricia D. Horoho announced a new health care strategy called the Performance Triad, emphasizing sleep, activity, and nutrition. While this may seem like stating the obvious, in the military world—where going without sleep is often an assumed part of (or consequence of) the job—it’s a big step.
Last September, Peterson, Raskind, and Peskind published the results of their prazosin trial in the American Journal of Psychiatry. It was the first successfully completed study ever of the effect of a specific medication on a behavioral disorder in active-duty service members. “Prazosin,” the article concluded, “is effective for combat-related PTSD with trauma nightmares in active-duty soldiers, and benefits are clinically meaningful.” The authors cautioned that prazosin does not “cure” PTSD but suggest there may be hope for combining drug and talk therapy.
Banks would agree. In addition to prazosin, Banks takes Xanax every day for anxiety and benefited from the Wednesday-night group therapy sessions. Like Banks, Bell avoids large crowds—sports arenas are out, movies are “hard” but he goes occasionally, if his three daughters, his niece, or his wife talk him into it. But neither Banks nor Bell would dream of missing a dose of prazosin.
In 2012, Raskind was awarded the John Blair Barnwell Award, the VA’s highest honor for clinical science research, “for his work on the biochemical pathways involved in post traumatic stress disorder, Alzheimer’s disease, and alcoholism. In particular, he was cited for spearheading the use of an inexpensive generic drug called prazosin to treat PTSD nightmares.” In October 2012, Raskind, Peskind, and their colleagues received the United States Department of the Army’s Commander’s Award for Public Service—the fourth-highest honor the army can bestow upon a civilian—for innovative research in treating Joint Base Lewis-McChord soldiers.
Their work has paved the way for other benefits of the drug. Working with active-duty soldiers led a colleague of Raskind and Peskind’s to another accidental discovery about prazosin. In some cases, it can prevent a pernicious type of migraine triggered by multiple traumatic brain injuries.
William Kerby took part in three Marine tours in Iraq, including the assault on Fallujah in the winter of 2004–05, in which he repeatedly—“hundreds of times”—used C4 explosives to blow open doors and gates. With nearly every blast, he said, he could “feel that concussion” go through his body. The worst one was when a few other Marines did not realize he was on the opposite side of a wall when they blew it up with eight pounds of explosives. (One-eighth of a pound was usually enough to blow a lock off.)
“It threw me across the room,” Kerby said. “I don’t think I lost consciousness, but I was kind of loopy” afterward.
Kerby, now 32 and the father of two children, ages three and five, didn’t pay much attention to the occasional headaches he began to experience. He got out of the Marines in 2006 and passed all his exit medical exams. But the headaches grew worse. He began missing work and family events. When he finally responded to a VA health survey form he’d been ignoring, he was immediately invited to come in and see a neurologist and a psychiatrist. The neurologist said he was fine. The psychiatrist referred him to Peskind, who was seeing a lot of veterans with traumatic brain injuries.
Peskind suggested prazosin. It took some time to get his dose straight—too much at once actually gave him a headache—but once they did, said Kerby, he felt like a new person, with “no more headaches than Joe Blow down the street.”
Kerby now works for a box and paper manufacturing company. Lately, he’s had to pull some double shifts. Quite a change from having to lie flat out on the couch with a migraine three to five times a week, unable to play with his son, who knew by the time he was three to ask, “Dad, do you have a headache?”
Peskind is about to launch a placebo-controlled trial of prazosin for postconcussive migraine. She and her team will be recruiting at both JBLM and the VA in Seattle.
Most of the 23 million veterans in the U.S. receive health care outside of the VA. But according to Raskind, roughly 600,000 veterans in the VA system have a diagnosis of PTSD in their charts. A majority of PTSD survivors do not have debilitating trauma nightmares, but of those being treated by the VA, Raskind says a conservative estimate of those who do is about 100,000.
Although only 17 percent of vets in the VA system diagnosed with PTSD are taking prazosin, Raskind says this may finally be about the right percentage, “because prazosin works for the ones who are having this distressing adrenaline storm associated with the nightmares and daytime hyperarousal. And for those folks who are not having that, the drug is not particularly helpful.”
In other words, nearly 20 years of word-of-mouth endorsements and modest publicity generated by small studies have ensured that most vets who could benefit from prazosin are at long last getting it.
Prazosin is being prescribed enough, though, that there have already been shortages, because it’s a generic drug manufactured by several companies without much financial incentive. Though these shortages have been less frequent in the past 18 months, Raskind says they “have caused substantial
distress among lots of vets,” because prazosin controls, but does not cure, symptoms. “It makes it better as long as you’re taking it. But if you stop, especially if you’ve had PTSD a long time, the nightmares and symptoms come back. It’s possible there’s something about reliving the experience at night for years and years that makes the symptoms more entrenched.”
As with the recent discovery that prazosin may alleviate postconcussive migraines in combat vets, Peskind and Raskind’s work with Alzheimer’s patients has led them to yet another potential use. They are launching a study to see if prazosin is effective in calming agitation in late-stage dementia patients.
Perhaps Raskind’s claim that he specializes in “patients who can’t remember and patients who can’t forget” is more than just an easy quip. It actually makes a lot of sense.