Pill helps alcoholics taper off drinking
Tue, 09 Oct 2007 21:41:53 GMTBy CARLA K. JOHNSON, Associated Press Writer
CHICAGO - A migraine pill seems to help alcoholics taper off their drinking without detox treatment, researchers report, offering a potential option for a hard-to-treat problem.
The drug, Topamax, works in a different way than three other medications already approved for treating alcoholism.
Experts said the drug is likely to appeal to heavy drinkers who would rather seek help from their own doctors, rather than enter a rehab clinic to dry out. The drug costs at least $350 a month, plus the price of doctor's visits.
But side effects are a problem, and it's unclear whether the findings will make a dent in an addiction that affects millions of Americans.
Addiction specialists not involved in the study said the findings are promising, although side effects such as trouble concentrating, tingling and itching caused about one in five people to drop out of the study. Drowsiness and dizziness are also problems.
"The size of the treatment effect is larger than in most of the other medications we've seen," said Dr. Mark Willenbring of the National Institute on Alcohol Abuse and Alcoholism. "And all the drinking variables changed in the right direction."
The study, published in Wednesday's Journal of the American Medical Association, was funded by the maker of the drug, Johnson & Johnson Inc.'s Ortho-McNeil Neurologics. The researchers also reported financial ties to the company. Ortho-McNeil reviewed the manuscript, but did not change the results or interpretation, the researchers reported.
The study followed 371 heavy drinkers for 14 weeks. About half were randomly assigned to take Topamax, also called topiramate, in gradually increasing doses. The others took dummy pills.
All volunteers were encouraged — but not required — to stop drinking.
At the start of the study, they drank, on average, 11 standard drinks daily. That's about two six-packs of beer each day, or two bottles of wine, or a pint of hard liquor.
By the end of the study, 27 of the 183 people, or 15 percent, who took Topamax had quit drinking entirely for seven weeks or more. That compared to six out of 188, or 3 percent, in the placebo group.
Others cut back. The Topamax group cut back to six drinks a day, on average, assuming everyone who dropped out of the study relapsed into heavy drinking. That compared to seven drinks a day for the placebo group.
"You can come in drinking a bottle of scotch a day and get treatment without detox," said Dr. Bankole Johnson of the University of Virginia, who led the study, which was conducted at 17 U.S. sites from 2004-2006.
The study didn't follow the drinkers long-term, so it's unclear how many relapsed after they stopped taking the pill.
But there were lasting effects for Tom Wolfe, 44, a carpenter from Earlysville, Va., who said he has been sober for two years thanks to Topamax. After years of heavy drinking, he took part in an earlier Topamax study. He felt "a little lightheaded" at first until he got used to the drug. Alcohol lost its enjoyment, strengthening his resolve to quit.
"It's been a miracle to me," Wolfe said. "It got the monkey off my back."
The drug works by inhibiting dopamine, the brain's "feel-good" neurotransmitters that are involved in all addictions, said Stephen Dewey, a neuroscientist the Brookhaven National Laboratory, who was not involved in the study but does similar research.
It's a new approach, he said, that "clearly did work on a very small subset in the population."
Willenbring, who wrote an accompanying editorial, predicts that a future pill, although probably not Topamax, will do for alcohol dependence what Prozac did for depression: Remove the stigma.
Prozac changed the nature of depression treatment 20 years ago by allowing patients to see their family doctors for help, Willenbring said. An effective drug with few side effects could do the same for alcoholism treatment, he said.
"This is a huge market," Willenbring said. "We're approaching a Prozac moment."
But Topamax has big obstacles. With the drug maker's patent expiring next year, there won't be any big push to advertise it for alcoholism, Willenbring said.
Doctors are free to prescribe drugs for uses that have not been approved, but drug companies are prohibited by law from marketing drugs for these so-called "off-label" uses.
On Tuesday, Dr. Sidney Wolfe, director of Public Citizen's health research group, sent a protest letter to the U.S. Food and Drug Administration questioning the promotion of Topamax for alcoholics by researchers funded by Ortho-McNeil.
"This is a very bad message to send out," Wolfe said.
Ortho-McNeil has no plans to seek federal approval for the drug as an alcoholism treatment and promotes it only for its approved uses of migraine prevention and epilepsy, said company spokeswoman Tricia Geoghegan. The company dropped development of new uses for the drug in 2004, but has continued to support some research.
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Studies tout treating ministrokes fast
Tue, 09 Oct 2007 12:00:32 GMTBy MARIA CHENG, AP Medical Writer
LONDON - Treating patients quickly for mini-strokes could dramatically cut the risk of a major stroke later, report two studies that could change standard treatment and potentially save millions of people from stroke's damaging effects.
In research published Tuesday, British and French doctors found that patients treated within 24 hours of having a mini-stroke cut their chances by 80 percent of having a more serious stroke in the next three months.
Such large reductions in risk are rare, said Dr. Peter Rothwell of Oxford University, lead author of a study published in The Lancet medical journal. "We normally get excited about 10 to 15 percent."
Rothwell said that minor strokes should now be classified as medical emergencies. "The health care system needs to be changed to respond to these people quickly," he said. "The current delays in treatment in the United Kingdom are no longer acceptable."
In the U.K., most patients who have small strokes are referred by their doctors to specialist clinics. Many wait several weeks before being treated.
In the United States too, many people are sent home within a day if their symptoms seem to resolve.
Worldwide, nearly 15 million people have a stroke every year, and it is one of the leading killers in the industrialized world.
Mini-strokes, or transient ischemic strokes, have the same symptoms as a big stroke, including facial numbness, slurred speech, paralysis on one side of the body, blurry vision or a sudden headache. But in small strokes, the symptoms last less than a day.
Rothwell's research was drawn from a larger population of nearly 100,000 people being studied for vascular disease. Of 1,278 patients who had a stroke or a mini-stroke, he and colleagues examined roughly 600 people who had mini-strokes.
In the first part of the study, 310 mini-stroke patients were observed as they received standard care, under British medical guidelines. They were referred to an outpatient clinic. After a normal wait of about three weeks, these patients were typically prescribed drugs, including aspirin, to lower their blood pressure and cholesterol, and to prevent clotting.
In the second part of the study, about 281 other patients were given these same medications within 24 hours of their suspected mini-stroke.
The researchers found that the patients treated immediately had only about a 2 percent chance of having a major stroke in the next three months. In comparison, patients who weren't treated as quickly had about a 10 percent chance of having a major stroke in the next three months.
And among those who got delayed treatment, 32 had a bigger stroke. Among those in the group that got fast treatment, only six had a more serious stroke.
The study was funded by Oxford University. Rothwell has occasionally consulted for pharmaceutical companies that make drugs used in stroke prevention.
Similar research was published in Lancet Neurology. Dr. Pierre Amarenco of Bichat-Claude Bernard University Hospital in Paris and colleagues set up a 24-hour clinic to treat patients with suspected mini-strokes.
Among the 1,085 patients followed, the chance that patients would have another stroke within 90 days was a little over 1 percent. That compares to a predicted stroke rate of nearly 6 percent, based on historical medical data.
The Paris study was funded by a French non-profit organization. The authors said they had no conflicts of interest.
Doctors increasingly say that small strokes should be seen as warning signals for a more dangerous stroke later on, in the same way that chest pain can be a red flag for an imminent heart attack.
"We need to think of transient ischemic strokes as the 'angina' or 'acute coronary syndrome' equivalent for the brain," said Dr. Ralph L. Sacco, chairman of neurology at the University of Miami, who was not connected to the study. Sacco said that patients who have mini-strokes are at high risk of a more serious stroke and should be monitored more carefully.
The British Stroke Association said that Rothwell's study should lead to faster treatment of mini-strokes.
"We clearly should not be evaluating stroke symptoms in a leisurely sort of way," said Dr. Larry Goldstein, director of Duke University's Center for Cerebrovascular Disease, who was not connected to the studies. "The main message from these studies is that treatment delays can be dangerous."
Studies Stored blood lacks nitric oxide
Tue, 09 Oct 2007 03:06:20 GMTBy RANDOLPH E. SCHMID, AP Science Writer
WASHINGTON - Much of the stored blood given to millions of people every year may lack a component vital for it to deliver oxygen to the tissues. Nitric oxide, which helps keep blood vessels open, begins breaking down as soon as blood goes into storage, two research teams report in separate studies in this week's online edition of Proceedings of the National Academy of Sciences.
In recent years, doctors have become increasingly concerned about levels of heart attack and stroke in patients receiving transfusions and the new findings may help explain that.
"It doesn't matter how much oxygen is being carried by red blood cells, it cannot get to the tissues that need it without nitric oxide," said Dr. Jonathan Stamler of Duke University, leader of one of the research groups.
Blood vessels relax and constrict to regulate blood flow and nitric oxide opens up blood vessels, allowing red blood cells to deliver oxygen, he explained.
"If the blood vessels cannot open, the red blood cells back up in the vessel and tissues go without oxygen. The result can be a heart attack or even death," he said.
"The issue of transfused blood being potentially harmful to patients is one of the biggest problems facing American medicine," said Stamler.
Several of the researchers, including Stamler, have consulting and/or equity relationships with Nitrox/N30, a company developing nitric oxide based therapies.
The second research team, led by Dr. Timothy McMahon, also at Duke, studied the changes in stored blood over time. Currently blood is allowed to be kept in blood banks for up to 42 days. After that it must be discarded. An estimated 14 million units of red blood cells are administered to about 4.8 million Americans annually.
"We were surprised at how quickly the blood changes — we saw clear indications of nitric oxide depletion within the first three hours," McMahon said in a statement.
Stamler said in a telephone interview that the researchers knew that nitric oxide is responsible for opening up small blood vessels, but had not previously measured the amount of that chemical in stored blood.
"Surprisingly, we found blood depleted profoundly by day one and it remained depleted through day 42," he said.
But if they restored the nitric oxide at any point, the red blood cells were again able to open blood vessels and deliver oxygen to tissues, they said. They tested the blood with added nitric oxide both in the laboratory and in dogs.
"This is an important observation and it needs to be followed up," said Dr. Louis Katz, a past president of America's Blood Centers, which provides about half the nation's blood.
"If you are going to store red cells, is there a way to make sure appropriate nitric oxide levels are maintained?" said Katz, who was not part of the research teams.
It is possible that these findings may make the public concerned about transfusions, Katz said: "There is no doubt, if you are bleeding to death from a trauma" you need a transfusion.
Stamler agreed that "physicians need to be able to give blood if people are bleeding profusely."
Overall, Katz said: "This is neat research. It needs to be proven that it's clinically relevant."
Stamler agreed on the need for clinical trials.
"Banked blood is truly a national treasure that needs to be protected," Stamler said. "Blood can be life saving, only it is not helping the way we had hoped and in many cases it may be making things worse. In principle, we now have a solution to the nitric oxide problem — we can put it back — but it needs to be proven in a clinical trial."
The research was supported by the National Institutes of Health, Duke Anesthesiology Fund, the American Heart Association and N30 Pharma, which has a license agreement with Duke to develop nitric oxide-based therapies.
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Study ties marital strife heart disease
Tue, 09 Oct 2007 04:28:04 GMTBy LINDSEY TANNER, AP Medical Writer
CHICAGO - A lousy marriage might literally make you sick. Marital strife and other bad personal relationships can raise your risk for heart disease, researchers reported Monday.
What it likely boils down to is stress — a well-known contributor to health problems, as well as a potential byproduct of troubled relationships, the scientists said.
In a study of 9,011 British civil servants, most of them married, those with the worst close relationships were 34 percent more likely to have heart attacks or other heart trouble during 12 years of follow-up than those with good relationships. That included partners, close relatives and friends.
The study, in Monday's Archives of Internal Medicine, follows previous research that has linked health problems with being single and having few close relationships. In the new study, researchers focused more on the quality of marriage and other important relationships.
"What we add here is that, 'OK, being married is in general good, but be careful about the kind of person you have married.' The quality of the relationship matters," said lead author Roberto De Vogli, a researcher with University College in London.
De Vogli said his research team is doing tests to see if study participants with bad relationships have any biological evidence of stress that could contribute to heart disease. That includes inflammation and elevated levels of stress hormones.
Another recent study also looked at quality of relationships but had different results. There was no association between marital woes in general and risks for heart disease or early death. But it did find, over a 10-year follow-up, that women who keep silent during marital arguments had an increased risk of dying compared with wives who expressed their feelings during fights. What appeared to matter more for men was just being married; married men were less likely to die during the follow-up than single men.
That study, of nearly 4,000 men and women, was published online in July in the journal Psychosomatic Medicine.
In De Vogli's study, men and women with bad relationships faced equal risks. Volunteers filled out questionnaires asking them to rate the person to whom they felt closest on several measures. These included questions about to what extent does that person "give you worries, problems and stress?"
They also were asked about whether they felt they could confide in that person, or whether talking with that person made them feel worse.
Over the following 12 years, 589 participants had heart attacks or other heart problems. Those with the highest negative scores on the questionnaire had the highest risks, even taking into account other factors related to heart disease such as obesity, high blood pressure and smoking.
James Coyne, a University of Pennsylvania psychology professor who also has examined the health impact of social relationships, said De Vogli's results "make intuitive sense." But he said the study found only a weak association that doesn't prove bad relationships can cause heart disease.
"It is still not clear what to recommend," Coyne said.
"Do we tell people who have negative relationships to get therapy? They may have other reasons to do so, but I see no basis for them doing so only to avoid a heart attack," Coyne said.
Ending a bad marriage is not necessarily the answer either, he said, given evidence that being unmarried also could be a risk.
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