New therapy holds hope for lives invaded by anxiety.
Researchers are optimistic that the drug will help people like Jones* and that once the word is out, more people with panic disorder will seek help.
LAST FEBRUARY, Cathy Jones family gave her a special Valentines Day gift: a tripaloneto Las Vegas. What should have been a relaxing, solitary vacation was instead a scary nightmare, at least while Jones was in the air.
On the plane to Las Vegas, she began to have trouble breathing. She was lightheaded, dizzy and overwhelmed with fear. A panic attack. Not her first, but they never get any easier.
I finally made it to Las Vegas, got off the plane, and I was fine, Jones recalls. I didnt have any problems while I was there. But when I went to the airport to check in and come home, I couldnt get on the plane.
Finally, Jones forced herself, deciding that if she didnt, she might never see her husband and son again. But she spent most of the flight home in the planes bathroom, literally sick with worry. Not all plane rides have had that effect on her. Nor have they been the only trigger for her panic attacks. Jones never knew what would set off her next attack.
Jones experience is typical for those with panic disorder, a condition that occurs in 1.5 to 3.5 percent of the population. Some people associate their panic attacks with particular events or circumstances like flying in a plane. But they dont have to be associated with anything, according to Keith E. Isenberg, MD, associate professor of psychiatry at the School of Medicine.
The most important dimensions of panic disorder are the rapid onset of symptoms, which are much more extensive than would occur in common anxiety, say before giving a speech, he says. Another important part of panic disorder is the anxiety that lingers between attacks. That can be as disabling, or more disabling, than the attacks themselves.
Isenberg is principal investigator for the St. Louis site of a multicenter study testing pregabalin, an investigational drug that has shown early promise in treating panic disorder. Preliminary results suggest the drug works quickly without many of the unpleasant side effects that accompanied past drug therapies for panic disorder.
Years ago, researchers made the serendipitous observation that drugs called tricyclic antidepressants not only eased depression, but also helped to control panic attacks in depressed patients. From there, it was a short step to determine that the drugs also helped to control panic attacks in patients who were not depressed.
Since then, newer antidepressant drugs called Selective Serotonin Reuptake Inhibitors (SSRIs) have been tested in patients with panic attacks. Those drugs are somewhat effective, too. But Isenberg says neither type of medication is ideal.
Antidepressants can take several weeks to work sometimes even a month, or moreand they can cause unwanted side effects in some patients, such as jitteriness, sexual dysfunction or gastrointestinal problems, he says.
Benzodiazepines are another class of drugs that has proven useful in panic attacks. These drugs are known to enhance the function of a particular neurotransmitter in the brain called GABA (gamma-aminobutyric acid). The GABA molecule is the brains major inhibitory neurotransmitter.
In the brain, benzodiazepines enhance the effectiveness of GABA, particularly at type A GABA receptors on neurons. Clinically, the drugs frequently provide almost instantaneous relief from panic attacks.
But some patients develop tolerance over time, and the drugs are no longer effective, Isenberg says. Plus, benzodiazepines can be associated with excessive sleepiness, clumsiness and memory problems.
Even so, the GABA connection was worth exploring further because some anti-seizure medications work by enhancing GABA production. Isenberg and other researchers have wondered whether panic attackswith their heart palpitations, breathing difficulties and other physical symptomsmight be some type of emotional or behavioral seizures. One drug that has been tested is gabapentin.
There is some evidence that gabapentin, and other drugs like it, enhance the amount of GABA available at the nerve terminals where the neurotransmitter is released, Isenberg says.
In this study, Isenberg is investigating a related drug, pregabalin. Like gabapentin, pregabalin is thought to increase the amount of GABA available at receptor sites on neurons.
The theory is that releasing GABA at those specific sites increases the inhibitory tone of the nervous system and, presumably by that mechanismand this is not really clear, by the waydecreases anxiety, Isenberg says.
Diagnosing the problem
Although she had suffered attacks off and on for more than a decade, Cathy Jones wasnt aware she had panic disorder until after her Las Vegas trip.
The Sunday after I returned, I saw an ad in the newspaper and responded to it. I told them what my symptoms were, and they told me to come in as quickly as possible, Jones recalls.
When she called the phone number in the ad, the voice on the other end of the line belonged to Theresa Kormos, coordinator for the pregabalin study.
Its not unusual for a person not to know whats wrong or to think theyre the only one in the world who suffers from these attacks, says Kormos. Many patients with panic disorderlike those with other psychiatric illnessesnever get plugged into the mental health system.
For 13 years, a parade of doctors had told Jones various things about her attacks. One neurologist said she had a brain tumor, another told her that when she was under stress, her brain stem rubbed up against one of the bones in her spine, leading to the attacks.
People with panic disorder are frequently evaluated by primary care physicians or by specialists because their physical symptoms can be so striking, says Isenberg. Many receive cardiac stress tests, tests of lung function or evaluations of their gastrointestinal systems."
Although many doctors had evaluated Jones over the years, none had figured out what was actually wrong or how to treat it. She had undergone numerous tests, but when all was said and done, the consensus was that she simply would have to live with her problems.
Panic disorder typically strikes people in their late teens through 30s. During attacks, patients often report a racing heart, shortness of breath, chest pain, upset stomach or some combination of those symptoms.
Attacks come suddenly, can become disabling in just a few minutes and typically last for about an hour. Although many people have attacks, only those who continue to experience anxiety between their attacks are classified as having panic disorder.
Pregabalin therapy may alleviate the symptoms of this paralyzing form of dread.
It seems to have done that for Cathy Jones. She was randomized into the active arm of the study, and Kormos and Isenberg explained to her that she might receive an inactive placebo. She quickly realized that she had not.
I knew within three days, Jones recalls. My body told me that it felt different. I just knew I wasnt on a sugar pill.
Jones has since been part of the open-label group of patients. After completing the initial 12-week study, she was offered an opportunity to continue taking the study drug.
It was an easy decision, considering that she has not had a panic attack since last winter. That followed six months in which the attacks were coming almost daily.
A possible solution
Jones never sought the psychiatric help she needed because she was secretly worried that she was crazy, and she thought a psychiatrist might confirm that fear.
I would think, When will I have another attack? What am I going to be doing when it happens? What if Im in a car? What if I have my son with me? For me, the fear of having people think I was crazy was as bad as the attacks themselves, she says.
Cathy is fairly typical of the patients we see, says Kormos. She had been told so many things over the years, and no one had been able to make the problem go away. Because so few of these patients get proper treatment, after a while people like Cathy can begin to think that they, themselves, are the problem.
Kormos and Isenberg are optimistic that pregabalin will help people like Jones and that once the word is out, more people with panic disorder will seek help.
No treatment is going to work for everybody all of the time, Isenberg warns. We simply want something thats very safe and can help some people with panic disorder. It appears possiblewe have to wait for the results of the trialthat this medication may offer those things.
*Cathy Jones is a pseudonym