Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1999-09-16
2003-04-01
Jones, Dwayne C. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S282000, C514S321000, C514S326000, C514S398000, C514S399000, C514S401000, C514S652000, C514S657000
Reexamination Certificate
active
06541478
ABSTRACT:
This invention relates to the use of opioid antagonists such as naltrexone, naloxone or nalmephene alone or with either nicotine replacement therapy or with other withdrawal attenuating agents, to increase smoking abstinence rates, to decrease craving for cigarettes, reduce relapse to heavy smoking during detoxification or once smoking abstinence has been achieved, and to reduce weight gain associated with smoking cessation.
DESCRIPTION OF THE RELATED ART
Tobacco dependence continues to be a major health hazard for millions of Americans, and because smoking may pose a health risk for non-smokers as well, smoking cessation treatments are of great public interest.
Dependence is an adaptive biological state induced by chronic drug exposure which manifests itself in various behavioral and physiological responses when drug exposure ceases. Withdrawal from nicotine following chronic use of tobacco products results in the emergence of an abstinence syndrome which reaches its peak intensity within the first day. Cessation of smoking has been shown to result in a number of signs and symptoms of withdrawal such as increases in irritability, anxiety, restlessness, impatience, somatic complaints, cigarette craving, hunger, insomnia, tremulousness and heart rate as well as difficulty concentrating, all of which are collectively called the tobacco withdrawal syndrome.
In recent years, research efforts have focused on nicotine replacement strategies to treat nicotine withdrawal following smoking cessation. A transdermal nicotine delivery system popularly called the nicotine patch was introduced in 1992. Reported short term success rates for nicotine patch treatment range between 19% after three weeks in a study without concomitant support to 54% with support. In general, nicotine replacement results in quit rates approximately twice that of placebo patches. Detoxification using the nicotine patch may have limited success, in part, because of the long time frame (typically 8 weeks or more) specified for this procedure. Although active patch success rates at six months continue to be better than placebo, they are substantially lower than at the end of active treatment and range from 4% to 43% among active patch users compared with 0% to 30% in placebo patch users depending on the level of psychosocial treatment provided. This suggests the need for new treatments to prevent relapse following detoxification. The significant problem of weight gain observed with smoking cessation, particularly in women, has not been ameliorated by nicotine replacement strategies, and is often cited as a reason for relapse or for not attempting to quit.
The alpha-2 agonist clonidine is used in anxiety disorders and to decrease the abstinence reactions associated with opiate and alcohol withdrawal. Clonidine has also been tried as an alternative treatment for nicotine addiction. Two large placebo controlled trials of oral clonidine indicated that smoking cessation rates were no better that placebo (Davison, et al.,
Clinical Pharmacol Ther
44:265-7, 1988; Franks, et al.,
JAMA
261:3011-3, 1989). Since oral clonidine is associated with too many side effects other investigators tried to use transdermal clonidine. A double-blind randomized trial of transdermal clonidine in heavy smokers demonstrated that the success rates of smokers on clonidine was twice that in the placebo treated group (Glassman, et al.,
JAMA
259:2863-6, 1988) and a recent meta-analytic review confirms the doubling of quit rates with clonidine (Covey, et al.,
Br J Addiction
86:991-998, 1991). However, other investigators have found that transdermal clonidine attenuated nicotine withdrawal but did not increase smoking cessation (Prochazka, et al.,
Arch Intern Med
152:2065-9, 1992). A recent study of transdermal clonidine with and without behavior modification failed to demonstrate substantial benefits of clonidine over placebo. Clonidine was superior to placebo only in patients receiving behavior modification only at 6 weeks after smoking cessation (Hilleman, et al.,
Annals of Pharmacotherapy
27:1025-1028, 1993). Therefore, although clonidine is known to reduce nicotine withdrawal the efficacy of clonidine as a treatment for nicotine addiction remains controversial.
It would be desirable to have alternate treatments for nicotine cessation (detoxification) that are rapid, to prevent relapse during more gradual detoxification and after nicotine withdrawal, and to reduce weight gain typically observed during and after nicotine withdrawal.
BRIEF SUMMARY OF THE INVENTION
It is an object of the invention to provide new smoking cessation treatments.
It is a further and more specific object of the invention to provide smoking cessation treatments that yield optimal smoking cessation rates.
It is another object of the invention to provide a method for “rapid” (and “ultra rapid”) detoxification from nicotine in order to shorten the time required for detoxification and to facilitate smoking cessation.
It is another object of the invention to provide a method for minimizing weight gains often associated with smoking cessation.
It is an additional abject of the invention to provide a method for preventing relapse after completion of nicotine detoxification.
These and other objects are provided by the present invention which provides methods for treatment of persons with nicotine dependency. These include methods for “rapid” (and “ultra rapid”) detoxification from nicotine; methods for preventing relapse during more gradual detoxification and after cessation of nicotine intake; and methods for reducing weight gains during and after nicotine detoxification, by administration of an effective amount of an opioid antagonist such an nalmefene, naloxone, naltrexone, or a mixture of any of these. Naltrexone is used in one embodiment.
The invention further provides methods for treating a person for nicotine dependency by administering to the person a combination of an effective amount of an opioid antagonist such as naimefene, naloxone, naltrexone, or a mixture of any of these, and an effective amount of at least one other compound that enhances the nicotine dependency treatment such as an effective amount of a withdrawal attenuating agent. Embodiments include the use of nicotine, typically by employment of a transdermal nicotine delivery system, nicotine chewing gum, nicotine inhaler, other nicotine delivery methods, and/or administration of other compounds that manage nicotine withdrawal symptoms and/or enhance nicotine dependency treatment (e.g., antihypertensives, antidepressants, antianxiety agents, serotonergic agents, and the like) with an opioid antagonist; use of an opioid antagonist while the person is under sedation or anesthesia; and use of a withdrawal attenuating agent and an opioid antagonist after pretreatment with the attenuating agent.
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O&a
Krishnan-Sarin Suchitra
Meandzija Boris
O'Malley Stephanie
Jones Dwayne C.
Krinsky Mary M.
Yale University
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