A widely used high-blood-pressure drug has emerged as the first of what experts foresee as a growing number of nicotine-free chemicals capable of weaning smokers from their habit.
In the process of testing the drug, clonidine, drug-dependence researchers have concluded that, because of the success of anti-smoking programs, most of those who still smoke probably represent a hard core of addicted users for whom conventional cessation strategies will have only limited effect.
In addition, the research on the drug--commonly sold under the brand name Catapres--confirmed a 1986 finding that smoking is highly likely to be associated with a medical history of depression.
The observations about clonidine, published in today's issue of the Journal of the American Medical Assn., come in the wake of Monday's annual smoking report by U.S. Surgeon General C. Everett Koop that underscored the addictive potential of tobacco, linking it in habit-forming potential to heroin and cocaine.
The new clonidine study, led by a prominent New York expert on depression, appears to underscore what researchers say is a growing sense of how intractable smoking behavior can be. An editorial published with the new study predicts that clonidine will open the way for development of a family of nicotine-free drug treatments to help smokers quit.
Until now, only chewing gum, stick-on patches and nasal spray--all containing nicotine--have been available as pharmacologic smoking treatments. In an effort to eliminate nicotine products from smoking treatment, researchers have experimented with another blood pressure drug, mecamylamine (brand name: Inversine) and two anti-depressants, fluoxetine and doxepin--all with only modest success. Some research subjects have reported side effects common to psychoactive drugs. And researchers at UCLA are still testing an inhalant made from the active ingredient in lemon juice, though results are not expected for several months.
But to Dr. John Hughes, a University of Vermont expert on tobacco addiction, the new study of clonidine--which appears the most promising of all the nicotine-free agents tested so far, he said--represents a direction that has developed, virtually from scratch, since 1985.
"Three years ago, if you'd mentioned the idea that drugs (to treat smoking) are going to become more common, people would have said, 'You're crazy,' " Hughes said in a telephone interview. "(Today) we're right on the border of really starting to understand the mechanism of tobacco dependence. As we understand that, we'll see a lot more rational medication therapy going on."
Hughes and Dr. Daniel Freedman, a UCLA psychiatry and addiction expert, said researchers have begun to focus on an area of the brain called the locus ceruleus, which has also been identified as having a role in addiction to other psychoactive drugs. As an anti-hypertension medication, clonidine is thought to interfere with the brain's control over the manufacture of natural adrenaline and to prevent dangerous increases in blood pressure. Since some of the same adrenaline function is believed responsible for addictive behavior, researchers think clonidine's blood pressure effect is applicable to addiction treatment.
In the study of clonidine, a team of researchers at the New York State Psychiatric Institute and Columbia University tested the drug on 77 smokers trying to quit. Forty-five of them were given daily doses of the drug in the same amounts used for blood pressure treatment while the rest received a placebo. The clonidine group as a whole was able to give up smoking far more readily than the placebo group; clonidine was especially effective in women, for whom it was successful 72% of the time.
Overall, clonidine was effective for 64% of the subjects after four weeks' use. Dr. Alexander Glassman, who headed the research, said the different success rates between men and women may have been due to statistical quirks.
Six months after the clonidine treatment, Glassman said, the drug-treated group showed about the same success in staying off tobacco as patients elsewhere who were given nicotine gum or another nicotine product. Six months after the study, 27% of the group that received clonidine was still not smoking compared to 5% of those who got the placebo.
Success rates in smokers who reported histories of depression were significantly lower than in those who did not. A total of 75% of subjects who were free of depression successfully completed clonidine treatment, while 52% of those who had been through periods of depression earlier in their lives did so.
"We figured that it was going to be tough enough to get people to stop smoking without their being depressed or drug abusers," said Glassman. "But what we didn't expect was the effect of depression. Our sample was heavily addicted (to tobacco) and it follows Koop's concerns. These are hard-core smokers.