New Assaults on Addiction

Research suggests drinking and smoking go hand in hand with anxiety -- and that's opening novel approaches for treatment

Alcohol and nicotine. Two simple, naturally occurring chemicals that just happen to be highly addictive. The toll they exact in human suffering and the burden they impose on the economy are enormous. Alcoholism affects 1 in 5 men and 1 in 10 women in the U.S., and is a factor in 44% of the country's estimated 40,000 annual traffic fatalities, according to the National Institute on Alcohol Abuse & Alcoholism (NIAAA). The institute estimates alcohol's economic impact to be nearly $185 billion in 1998. Despite declines in the number of smokers, tobacco is responsible for 430,000 deaths each year, according to the Centers for Disease Control. The bill: $100 billion in medical and indirect costs.

Worse yet, those addicted to one substance who use the other are likely to be addicted to that, too. As a look inside most local pubs may confirm, studies have shown that smokers consume twice as much alcohol as nonsmoking tipplers. The odds of a smoker also being an alcoholic are twice that of the nonsmoking drinker.

Significantly, while the percentage of smokers has dropped below 30% of American adults, between 80% and 95% of alcoholics still smoke. Indeed, they're more likely to die of smoking-related diseases, such as lung cancer and heart disease, than those associated with alcohol, such as cirrhosis.

But over the past decade, neuroscientists and psychiatrists have made rapid progress in untangling the complex links between nicotine and alcohol addictions. And researchers have recently discovered another common denominator in many such addicts -- chronic anxiety, and sometimes, related depression. Increased understanding of the links among them is leading to new medications and approaches to treating the often-deadly addictions.


  Once trivialized as the malady of the "worried well," anxiety is now recognized as having passed depression as the most common mental illness. The National Institute of Mental Health estimates that more than 19 million Americans suffer from severe anxiety conditions, including panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, phobias, and generalized anxiety disorder. Left untreated, an anxiety disorder almost always worsens. For an estimated 43%, it leads to depression and abuse of alcohol and drugs.

Those suffering from so-called "trait" anxiety live in a nightmarish world of unfounded fears, obsessions, sudden unexplained panic, and irrational thoughts. A study conducted by the Anxiety Disorders Association of America estimates that anxiety costs the U.S. $42 billion annually. "People with anxiety disorders are high users of all kinds of medical services, from doctor visits to counseling sessions and hospital stays," said Ronald C. Kessler of the Harvard Medical School, who was one of the study's principal investigators.

Anxiety disorders often manifest frightening physical symptoms that cause sufferers to make repeated visits to the doctor. They exhibit a range of physical symptoms and have higher than average rates of asthma, irritable bowel syndrome, ulcers, inflammatory bowel disease, and coronary heart disease.

Researchers have discovered that addiction and anxiety share the same pathways in the brain

All too often, physicians fail to diagnose the underlying illness. As a result, fewer than one-third of sufferers of anxiety disorders receive appropriate treatment -- generally medication, therapy, or a combination. Anxiety "is very prevalent, yet frustrating to treat because physicians often fail to correctly diagnose it," says Jonathan Davidson, a psychiatrist at Duke University who headed tests of Wyeth Laboratories' antidepressant venlafaxinean to treat generalized anxiety.

Yet, the millions of people who suffer from dual addictions to nicotine and alcohol and also have underlying anxiety form a group that's most resistant to treatment -- and most prone to relapse. But researchers have discovered the reason that addiction and anxiety often go hand-in-hand: They share the same pathways in the brain.

Addictive drugs overstimulate the brain's so-called reward system -- a network of neurons and receptors that are normally activated when we do something essential to our survival, such as eating or having sex. The "high" occurs because the drug triggers the release of neurotransmitters, particularly dopamine and serotonin. Anxiety and depression have the opposite neurochemical basis -- sufferers have below-normal levels of serotonin and other neurotransmitters that induce pleasurable feelings.


  Increasingly, researchers are concluding that heavy smoking, alcohol abuse, and use of other drugs are an attempt on the part of those suffering from anxiety and/or depression to find relief. Alcohol, a central-nervous system depressant, has a long history of serving to calm people during times of stress. "Thirty years ago, we'd practically prescribe a double scotch to a guy about to make a speech," recalls one psychiatrist who now treats alcoholics and drug addicts.

One study found that the incidence of nicotine dependence was twice as high in young adults with anxiety disorders than in those with no psychological problems. In those with depression, the rate was three times as high and, when both anxiety and depression were present, four times. "Many of those who have given up smoking in the past appear to have been the 'easy quits' or casual adult smokers," says Cynthia S. Pomerleau, a researcher at the University of Michigan Substance Abuse Research Center. But for the hard-core 15% to 20% of smokers, quitting is extremely difficult. Their withdrawal symptoms persist the longest and their relapse rate is the highest.

And nicotine's relationship to alcohol? In a series of five studies, Dzung Anh Lo, a senior scientist at the Centre for Addiction & Mental Health at the University of Toronto, concluded that the connection between the two substances goes deeper than co-abuse. "We found that nicotine can promote alcohol consumption," says Lo.


  Its appears that both addictions have strong genetic links. The 10th Special Report to the U.S. Congress on Alcohol and Health, which the National Institute on Alcohol Abuse & Alcoholism published last November, reports that two studies have found evidence of genes that seem to influence susceptibility to alcoholism. Says Pomerleau: "Recent twin studies suggest that the heritability of smoking is at least as high as that of alcohol, with significant genetic contributions to initiation, age of onset, amount smoked, and likelihood of quitting."

Subjects with the gene for "fast uptake" of serotonin reported feeling more anxiety than the other group

Not surprisingly, genes seem to be implicated in anxiety, too. One, identified by researchers at Ohio State University last summer, regulates levels of serotonin in the brain. Some people have a variation in the gene, which causes neurons in the brain take up serotonin faster, leaving less available. In a study, subjects were asked to take breaths of air rich in carbon dioxide to induce shortness of breath -- and fear. Those with the gene for "fast uptake" of serotonin reported feeling more anxiety than the other group. The heart rates of those with lower serotonin levels remained elevated after the experiment. For the others, the rate dropped after it was clear to them they were in no danger. "People with the [gene] variation seem to be at greater risk for responding with high levels of anxiety or panic in fearful situations," says psychologist Norman Schmidt, who co-authored the study.

Researchers have also found that alcohol seems to have a different effect on people prone to anxiety. People highly susceptible to anxiety have a fear of the symptoms themselves. Feeling "butterflies" in the stomach, breathing rapidly, or experiencing an increased heart rate in the face of a stressful situation tends to amplify the anxious response. But for such people, alcohol has a greater "soothing" effect after a stressful situation than it does on the general population.


  To find out whether it's anxiety that drives alcoholics to drink or whether drinking causes anxiety, psychologists Alan B. MacDonald of Dalhousie University and Robert O. Pihl of McGill University asked participants to hyperventilate for three minutes to induce signs of anxiety and asked the subjects to describe their feelings. The group was asked to describe their feelings again after each of two doses of alcohol.

Those highly susceptible to anxiety reported more fearful thoughts and negative feelings than their lower-sensitivity counterparts. But after consuming alcohol, they reported greater relief than the other group. And the soothing effect became more pronounced the more they drank, which wasn't the case with the less-anxious group. "Our findings have opened a small window into why some people may learn to abuse alcohol," says MacDonald, who estimates that between one in six or seven people is highly susceptible to anxiety. "Knowing why leads to knowing what to do about it."

The new insights into alcoholism and smoking are already changing the way these addictions are treated. Just a few years ago, both alcoholics and smokers had few options beyond going "cold turkey" to kick their habits. Treatment meant little more than masking the effects of withdrawal -- tranquilizers to minimize anxiety and tremors, and vitamins to restore nutritional deficiencies.

After detoxifying, most recovering alcoholics continue to want to drink. They resist by joining support groups and "12 step" programs, such as Alcoholics Anonymous, taking it, as the saying goes, "one day at a time." Smokers could try to wean themselves from nicotine through programs such as Smoke Enders. For both groups, recovery is often painful -- and marked by frequent relapses.

Antabuse turns alcohol into a poison that causes horrible hangover symptoms

Until recently, only one drug was used for alcoholism, a draconian medication called disulfiram, or Antabuse. It would be considered only by the truly desperate. In use since 1948, Antabuse turns the slightest amount of alcohol into a poison that almost immediately causes the symptoms of the worst hangover any drinker can remember. Even the tiny amounts of alcohol in foods, mouthwash, or expensive chocolates can be enough to trigger the Antabuse.

Things began to change in 1995 when the Food & Drug Administration approved naltrexone for treating recovering alcoholics. Originally prescribed to help drug addicts avoid relapse, it blocks the opiod receptors in the brain that produce the characteristic "high" that comes from using drugs -- and alcohol. Social drinkers given naltrexone told researchers that they felt less stimulating effects from alcohol and more of the sedative effects, and they waited longer between their first and second drinks. Alcoholics treated with naltrexone resisted returning to drinking for a longer time than those given a placebo.


  Naltrexone is now also being tested to see if it reduces nicotine cravings in smokers. Smokers got their first alternative to replacements such as nicotine patches and chewing gum in the form of a mild antidepressant called bupropion. Marketed as Zyban by Burroughs Wellcome, it appears to mimic nicotine's ability to increase the amount of dopamine in the brain.

Meanwhile, the number of drugs under study is growing. A newer opiate antagonist called nalmefene shows promise of being more effective than naltrexone because it binds to more types of receptors and seems to be less toxic. In a preliminary study conducted in 1999, Barbara J. Mason and her colleagues at the University of Miami School of Medicine found in a 12-week trial that patients who received nalmefene were 2.4 times less likely to relapse to heavy drinking than those who received a placebo.

Another drug not yet approved in the U.S., known as acamprosate, targets different receptor systems in the brain that seem to be involved in maintaining alcohol dependence. This drug, which decreases voluntary alcohol intake, has been approved in France since 1989 and has been used to treat more than 1 million alcoholics in 30 countries. It's manufactured by Lipha in Lyon, France. The first U.S. test, conducted by Miami's Mason, produced results similar to those of 10 European studies. Lipha's U.S. unit, New York-based Lipha Pharmaceuticals Inc., has been granted investigational new drug status by the FDA and is hoping to win regulatory approval.

The notion of treating a drug problem with other drugs is now gaining acceptance

Serotonin is the target of the experimental drug ondansetron, which appears to be effective against early-onset alcoholism, an intractable form of the disease that occurs in young patients with a family history of alcoholism and a propensity for antisocial behavior. Test results revealed last summer by Bankole A. Johnson of the University of Texas Health Science Center found that alcoholics who took the drug had fewer drinks per day and fewer drinking days.


  The new drugs are convincing evidence that "the prospects for improving treatment outcome have never been better," insists Enoch Gordis, director of the NIAA. And, increasingly, the community dedicated to treating addictions, which has a tradition of being chary of using drugs to treat the effects of other drugs, is incorporating pharmaceutical interventions into their regimen of psychotherapy and counseling. "Things have changed. If a drug looks like it will help, we'll prescribe it," says Ray Haley, a counselor at the Weekend Center in Mount Kisco, N.Y., an alcohol- and drug-treatment center.

Another change is the attitude toward treating addictions to alcohol and nicotine as one. Where asking alcoholics in treatment to give up smoking was once considered to be imposing an unnecessary obstacle to their recovery, therapists are now concluding just the opposite. "Treatments for both alcoholism and smoking need to combine their efforts," says addiction researcher Stephanie S. O'Malley, a professor of psychiatry at Yale University School of Medicine. "Greater attention should be given to both [alcohol and nicotine] when we're developing and evaluating behavioral and pharmacological treatment options for either."

Among the first clinics to ask alcoholics to put away their cigarettes -- and even another plant-derived addictive substance, caffeine -- was the University of Texas Medical School. Since it became "smoke-free" in 1991, it has observed no change in the rate of premature discharge or the number of people who completed the program.


  Like scientists, clinics are also looking for co-factors to addiction -- all too often anxiety and depression. Antidepressants are playing a more important role in the treatment of alcohol and nicotine addition -- in particular, sertaline (Pfizer's Zoloft) and fluoxetine (Eli Lilly's Prozac). These drugs, which were developed in the mid-1980s, are generally known as "selective serotonin reuptake inhibitors" because they increase serotonin levels by blocking its reabsorption by neurons.

A number of studies suggest that SSRIs may help smokers and drinkers to indulge less, but the results have been inconclusive. A 1995 study found that Prozac helped smokers with depression to quit but had no effect on smokers who weren't depressed. "Some patients wouldn't need nicotine replacement once they received appropriate medications for their underlying conditions," says University of Michigan's Pomerleau.

A magic bullet that would simply stop a deadly addiction in its tracks would be a drugmaker's dream blockbuster. For now, it's not likely. Despite the rapid progress in neuroscience and pharmacology, the intertwined relationship between addiction and psychological disorders is far from being deciphered. No one knows why one person becomes addicted and another doesn't, or why a treatment that works for one person does nothing for another. "There are multiple reasons why things happen, and it's important to understand them before you get into any kind of treatment," says McGill University's Pihl.

As scattershot as today's treatments may be, if research continues at the pace it did over the last 10 years, that magic-bullet goal may be realized. "I'm confident that soon we'll be able to identify the genetic basis for a person's addiction, understand its biochemical basis, and intervene in a positive way," says the Weekend Center's Haley. Then, people may be able to put their minds at ease with regard to the toxic triple whammy of alcoholism, smoking, and anxiety.

Further Information:

National Institute on Alcohol Abuse & Alcoholism

National Institute of Drug Abuse

National Center for Health Statistics

Tobacco Information from the Centers for Disease Control

Anxiety Disorders Association of America

By Alan Hall in New York

Edited by Douglas Harbrecht

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