Anatomy of an Epidemic (20 page)

Rebound Anxiety with Valium

In this 1985 study by British investigators, the patients treated with Valium did not fare better than the placebo patients during the first six weeks. The Valium patients were then withdrawn from the drug and their anxiety symptoms soared, to a much higher level than the symptoms in placebo patients. Source: Power, K. “Controlled study of withdrawal symptoms and rebound anxiety after six week course of diazepam for generalised anxiety.”
British Medical Journal
290 (1985): 1246–48.

Patients withdrawing from benzodiazepines, it seemed, were becoming more anxious than they had ever been. Over the course of the next decade, Lader and other British physicians (most notably Heather Ashton, a doctor at the University of Newcastle upon Tyne who ran a withdrawal clinic) continued to investigate this problem, and they compiled a long list of symptoms that could bedevil those quitting a benzodiazepine. In addition to rebound anxiety, patients could experience insomnia, seizures, tremors, headaches, blurred vision, a ringing in the ears, extreme sensitivity to noise, a feeling that insects were crawling over them, nightmares, hallucinations, extreme depression, depersonalization, and derealization (a sense that the external world is unreal). Withdrawal, one patient told Heather Ashton, was like “living death … I thought I had gone mad.”

“These findings show very clearly that benzodiazepine withdrawal
is a severe illness,” Ashton wrote. “The patients were usually frightened, often in intense pain, and genuinely prostrated…. Through no fault of their own, the patients suffered considerable physical as well as mental distress.”
³⁰

Not all people withdrawn from benzodiazepines suffer in this way. The risk of suffering withdrawal symptoms varies according to how long a person has been on the drug, the potency of the benzodiazepine, and the speed of the drug-tapering process. A majority of patients who’ve taken a benzodiazepine for a relatively short time, such as a month or two, may be able to withdraw from it with little difficulty. However, some people experience withdrawal symptoms after taking a benzodiazepine for only a few weeks, and it can take a longtime user a year or longer to taper from the drug. More over, a small percentage of people suffer a “protracted withdrawal syndrome,” their anxiety remaining at elevated levels “for many months after benzodiazepine withdrawal,” Ashton observed.
³¹
Depression may deepen, and the odd perceptual symptoms—the depersonalization, the derealization, the sensation of insects crawling on the skin—can haunt a person for an extended period. Most alarming, a small percentage of long-term users never fully recover. “It is very worrying,” Lader said, in an interview. “Somehow there has been a change [in the brain]. I cannot say that everybody is going to recover back to normality when they come off long-term usage.”

In 1977, researchers discovered that benzodiazepines affect a neurotransmitter in the brain known as GABA. Unlike dopamine and serotonin, which transmit an “excitatory” message telling a neuron to fire, GABA (gamma-aminobutyric acid) inhibits neuronal activity. A neuron receiving the GABA message either fires at a slower rate or stops firing for a period of time. A majority of neurons in the brain have GABA receptors, which means that this neurotransmitter acts as the brain’s brake on neuronal activity. A benzodiazepine binds to the GABA receptor and, in so doing, amplifies GABA’s inhibitory effects. It pushes down on the GABA brake, so to speak, and as a result, it suppresses central nervous system activity.

In response, the brain decreases its output of GABA and decreases the density of its GABA receptors. It is trying to “restore normal GABA transmission,” British scientists explained in 1982.
³²
However, as a result of these adaptive changes, the brain’s braking system is now in a physiologically impaired state. Its braking fluid is low (GABA output), and its brake pads are worn (GABA receptors). As a result, when the benzodiazepine is withdrawn, the brain is no longer able to properly inhibit neuronal activity, and its neurons may begin firing at a helter-skelter pace. This overactivity, Heather Ashton concluded, may “account for many of the effects of withdrawal.”
³³
The anxiety, the insomnia, the sensation of insects crawling across the skin, the paranoia, the derealization, the seizures—all of these vexing symptoms may arise from neuronal hyperactivity.

If a person gradually tapers off from a benzodiazepine, the GABA system may slowly revert to normal, and thus withdrawal symptoms may be mild. However, the fact that some long-term users suffer “protracted symptoms” is probably “due to the failure of the [GABA] receptors to revert to their normal state,” Ashton said.
³⁴
Long-term benzodiazepine use, she explained, may “give rise not only to slowly reversible functional changes in the central nervous system, but may also occasionally cause structural neuronal damage.”
³⁵
In such cases, the GABA brake never again functions like it should.

Once researchers in the United States and the United Kingdom determined that benzodiazepines did not provide any durable relief from anxiety, an obvious question arose: Do these drugs, when taken on a continual basis,
worsen
the very symptom they are supposed to treat? In 1991, Karl Rickels at the University of Pennsylvania School of Medicine reported on a group of anxious patients who had tried to quit benzodiazepines three years earlier, and he found that those who had successfully gotten off the drugs were doing “significantly” better than those who had failed to do so.
³⁶
A few years later, he was back with a new study: When long-term
users withdrew from benzodiazepines, they “became more alert, more relaxed, and less anxious, and this change was accompanied by improved psychomotor functions.”
³⁷
Those who stayed on the benzodiazepines were more emotionally distressed than those who got off.

Others told of similar long-term results. Canadian investigators found that benzodiazepine usage led to a fourfold increase in depressive symptoms.
³⁸
In England, Ashton observed that those who stay on the drugs tend to became more ill: “Many patients find that anxiety symptoms gradually increase over the years despite continuous benzodiazepine use, and panic attacks and agoraphobia may appear for the first time.”
³⁹
These studies and observations told of a very problematic long-term course, and in 2007, French researchers surveyed 4,425 long-term benzodiazepine users and found that 75 percent were “markedly ill to extremely ill … a great majority of the patients had significant symptomatology, in particular major depressive episodes and generalized anxiety disorder, often with marked severity and disability.”
⁴⁰

In addition to causing emotional distress, long-term benzodiazepine usage also leads to cognitive impairment. Early on, researchers recognized that memory problems were associated with short-term use, and this led David Knott, a physician at the University of Tennessee, to warn in 1976 that “I am very convinced that Valium, Librium and other drugs of that class cause damage to the brain. I have seen damage to the cerebral cortex that I believe is due to the use of these drugs, and I am beginning to wonder if the damage is permanent.”
⁴¹
Over the next twenty-five years, reports of cognitive impairment in long-term benzodiazepine users regularly appeared in scientific journals. These studies told of people who were having trouble focusing, remembering things, learning new material, and solving problems. However, the patients “are not aware of their reduced ability,” Lader wrote, evidence that their self-insight was impaired as well.
⁴²
In 2004, a group of Australian scientists, after reviewing the relevant literature, concluded that “long-term benzodiazepine users were consistently more impaired than controls across all cognitive categories,” with these deficits
“moderate to large” in magnitude. The studies showed the “higher the intake, dose and period of use [of a benzodiazepine], the greater the risk of impairment.”
⁴³

Increased anxiety, increased depression, and cognitive impairment—all of these factors contribute to a decline in a person’s ability to function in society. In 1983, the World Health Organization noted a “striking deterioration in personal care and social interactions” in long-term benzodiazepine users.
⁴⁴
Another investigator reported that they end up with poor coping skills.
⁴⁵
In a study funded by Hoffmann-La Roche, the manufacturer of Valium, University of Michigan investigators determined that taking this drug was “associated with poor quality of life, poor performance in work and personal life, low social support, perceived lack of internal control, poor perceived health and high levels of stress.”
⁴⁶
Ashton determined that long-term use led to “malaise, ill-health, and elevated scores for neuroticism.”
⁴⁷
Benzodiazepines, she said, contribute to “job loss, unemployment, and loss of work through illness.”
⁴⁸

Such is the history told about benzodiazepines in the scientific literature. Moreover, it is a story easily traced, as Dr. Stevan Gressitt, who today is the medical director for Adult Mental Health Services in Maine, can attest. In 2002, he helped form the Maine Benzo Study Group, which was comprised of physicians and other health-care professionals, and it concluded that “there is no evidence supporting the long-term use of benzodiazepines for any mental health condition.” Benzodiazepines, Gressitt and his colleagues wrote, may “aggra vate” both “medical and mental health problems.” In an interview, I asked Dr. Gressitt whether those “problems” included increased anxiety, cognitive impairment, and functional decline. Was his understanding of the scientific literature, I wondered, the same as mine?

“Your words I don’t contradict or argue with,” he replied.
⁴⁹

The scientific literature reveals that benzodiazepines—much as the neuroleptics do—act like a trap. The drugs ameliorate anxiety for a short period of time, and thus they can provide a distressed person much needed relief. However, they work by
perturbing
a neurotransmitter system, and in response, the brain undergoes compensatory adaptations, and as a result of this change, the person becomes vulnerable to relapse upon drug withdrawal. That difficulty in turn may lead some to take the drugs indefinitely, and these patients are likely to become more anxious, more depressed, and cognitively impaired.

Here are the stories of three people who fell into the trap.

Geraldine Burns, a thin woman with dark red hair, still lives in the house she grew up in. She tells me her story while we sit in her kitchen, her elderly mother darting in and out.

Born in 1955, Geraldine was one of six children, and theirs was a happy family. Her father was Irish, her mother Lebanese, and their Boston neighborhood was known as “Little Lebanon,” a place where everybody definitely knew your name. Aunts, uncles, and other relatives lived nearby. At age eighteen, Geraldine started dating a boy who lived down the block, Joe Burns. “I’ve been with him ever since,” she says, and for a time their life unfolded just as Geraldine had hoped. She had a job that she enjoyed in human resources at a rehabilitation center, she and Joe had a healthy son (Garrett) in 1984, and they basked in their close-knit neighborhood. Geraldine—outgoing and energetic—was the constant hostess for gatherings of family and friends. “I loved my life,” she says. “I loved working, I loved my family, and I loved this neighborhood. I was the one who organized the reunion of my grammar school. I still had friends from kindergarten. I couldn’t have been more normal.”

However, in March 1988, Geraldine gave birth to a daughter, Liana, and she felt physically unwell afterward. “I kept telling the doctors and nurses that I felt like I weighed a thousand pounds,”
she says, and after a doctor ruled out an infection, he figured she must be anxious and prescribed Ativan. Geraldine came home from the hospital with a prescription for that benzodiazepine, and although it helped for a short while, months later she still felt something wasn’t right and so she went to see a psychiatrist. “She immediately tells me I have a chemical imbalance,” Geraldine recalls. “She says that I should keep taking the Ativan and assures me that it is harmless and nonaddictive. She tells me that I will have to take this drug for the rest of my life. Later, when I questioned her about this, she explained it this way: ‘If you were a diabetic you would have to take insulin for the rest of your life, wouldn’t you?’”

Soon her psychiatrist added an antidepressant to the Ativan, and as Geraldine struggled to take care of her daughter that first year, her emotions seemed numbed, her mind fogged. “I was in a daze half the time. My mother would call and I would tell her something, and she would say, ‘You told me that last night.’ And I’d say, ‘I did?’” Worse, as the months wore on, she found herself becoming ever more anxious, so much so that she started staying inside her house. Going back to her job in human resources at the rehabilitation center was now out of the question. At one point, after she stopped taking Ativan for a day or two, she had a “massive panic attack.” The federal government agreed that she was disabled by “anxiety” and thus eligible for a monthly SSDI payment. “Me, who was the most social person on the planet, is not able to go out,” Geraldine says, shaking her head in disbelief. “I wouldn’t go out unless my husband would take me.”