Prozac Nicotine Patch

This is a double blind placebo controlled study of sustained release bupropion as a smoking cessation aid in alcoholics undergoing treatment for their alcoholism. Participants (N=58) were enrolled within one week of entry into alcohol treatment from community and Veterans Affairs Substance Use Disorder programs. All participants received nicotine patch and were invited to attend a smoking cessation lecture and group.

Cigarette smoking and alcohol outcomes were measured at six months. Bupropion when added to nicotine patch did not improve smoking outcomes. One-third of participants on bupropion reported discontinuing the drug during weeks 1-4. Participants reported cigarette outcomes with nicotine patch which are similar to those seen in the general population.

All study participants significantly reduced cigarette use. Co-morbid affective disorder or anti-personality disorder did not affect outcomes. Alcohol outcomes were improved in those who discontinued cigarettes. IntroductionThe World Health Organization (WHO) reports that 1.3 billion children, women and men are cigarette smokers worldwide.

According to the WHO, almost 5 million tobacco-related deaths occur each year and almost half of cigarette smokers will die as a result of their nicotine addiction. While cigarette smoking has decreased to 24.9% of the United States population age twelve or older (2005), approximately 80-95% of alcoholics smoke cigarettes (; ). Smoking alcoholics smoke more than non-alcoholics (; ), are more nicotine dependent , may experience more severe nicotine withdrawal symptoms and are particularly vulnerable to significant medical sequelae of concomitant use of both drugs (; ). Tobacco, rather than alcohol, has been shown to be the leading cause of death among alcohol dependent patients previously treated for their alcoholism in an inpatient setting. Previous studies of smoking cessation in alcoholicsSmoking quit attempts result in quit rates at 6 months of 10-40% in the general population and 0-29% in alcoholics.

In a study of lifetime quit attempts, remarkably only 7% of alcoholics reported being successful in their quit attempts while 49% of the general population were able to discontinue cigarette use. In a meta-analysis of persons with substance use disorders, smoking abstinence rates for comparison and intervention groups were 6 and 7% respectively for those in addictions treatment and 15 and 20% for those in recovery at 6-12 months.The authors found the greatest intervention effects in those recent studies that provided nicotine replacement therapy. When alcoholics are compared across various stages of their disease, individual quit attempts result in quit rates of 3-19% at 4-6 months while in alcoholism treatment (;;;; ) and 9-29% at 4-6 months in alcoholics who reported they were no longer drinking (;; ). 6 Months12 MonthsGeneralPopulationPlacebo ± PSS10.3-18.8%(Daughton et al., 1998;; )8.7-15.6%(Daughton et al., 1998;; )NicotineReplacement +PSS18.5-28%(Daughton et al., 1998; Fioreet al., 1994;; )14.7-16.4%(Daughton et al.,1998; )Bupropion +PSS24.2-34.8%(; )19.6-30.3%Bupropion +NRT + PSS38.8%35.5%Alcohol PopulationCommunitySampleNRT+PSS25%AlcoholTreatmentPsychosocialsupport3-11%(;; a)0-9%(; a)NRT+ PSS10.8-19% (; b)12.8-17.6%Recovery fromAlcoholismPSS21-29%26-27%Bupropion +PSS24.3%. B16 weeks f/u.Two studies found no adverse effects of concurrently treating alcoholism and nicotine dependence while Joseph showed that delayed treatment may be superior to concurrent treatment. Another study suggests that smoking cessation reduces the risk of alcohol relapse and an analysis of Project MATCH (a large multi-site study comparing various alcohol treatments) participants showed that persons who discontinued cigarettes had a significant and durable reduction in alcohol intake at the time of smoking cessation which persisted for six months post cigarette cessation.

A number of studies have found a positive association between abstinence from cigarettes and alcohol in alcoholics (;; ). Bupropion as a potential treatment for smoking cessation in alcoholicsSustained release bupropion, an antidepressant, has been approved for the treatment of cigarette smoking. In a review of 19 placebo-controlled trials, bupropion doubled the odds of smoking cessation.

It has multiple pharmacologic effects including blocking the reuptake of dopamine and noradrenaline (; ) and the nicotinic acetylcholine receptors. Sustained release (SR) bupropion has been shown to be efficacious in the treatment of smoking cessation in the general population, in African-Americans and in those who have relapsed to smoking (;;; ). Preliminary studies suggest that bupropion may be useful in smoking cessation attempts in persons with schizophrenia and chronic post traumatic stress disorder (;; ). Bupropion has also been shown to have efficacy in cigarette smokers with a former history of alcoholism with and without a history of major depression. However, in a study of bupropion in outpatient smoking clinics in France, participants with mild to moderate alcohol problems quit smoking at about half the rate of persons with no alcohol problems at 6 months. Bupropion has not been studied as a smoking cessation aid in individuals being treated for their alcoholism. Treatment SettingsParticipants were recruited between September 2002 and October 2004 from two substance use disorder (SUD) treatment programs in Eastern Nebraska: the Veterans Affairs Nebraska Western Iowa Health Care System (VA NWIHCS) Omaha site and Catholic Charities Campus for Hope (CFH).

Participants were recruited at admission to residential and nonresidential outpatient programs. The study protocol and consent form were approved by the VA NWIHCS Institutional Review Board and Catholic Charities. EnrollmentA total of 1,064 persons entering SUD treatment at the study sites were screened for study eligibility within seven days of treatment entry. If a review of the patient's chart indicated that the individual met criteria for study entry, a screening interview with the prospective participant was conducted. InterventionParticipants were randomized in a double blind manner into the treatment or control group. The treatment group received bupropion SR 150 mg per day for three days to be followed by 150 mg twice daily for 60 days.

The control group received identical placebo capsules and was instructed to follow the same medication regimen. All participants were instructed to begin their capsules eight days before their quit smoking date. Both groups received nicotine patches and were instructed in their appropriate use. Participants were asked to initiate the patches on their targeted quit date and to follow a tapering regimen of 21 mg (four weeks), 14 mg (two weeks), and 7 mg (two weeks). Study ProtocolAt the time of study enrollment, participants completed a baseline questionnaire. Each of the following three weeks the participants met with study staff to assess tolerability and compliance with study medication and participation in alcoholism treatment. Participants were asked to attend a single one hour smoking cessation group in which an educational video was shown and followed by a staff-lead discussion of smoking cessation techniques.

At week four, medication tolerability and compliance, cigarette smoking and alcohol outcomes were measured. At week nine and at six months, cigarette smoking and alcohol outcomes were measured.Participants received $10, $20, and $30 dollars at week 4, week 9 and 6 months respectively upon completing follow-up questionnaires. Participants were asked to return any unused nicotine patches and all bupropion/placebo medication bottles. The majority of participants were seen by the study coordinator at their treatment site during the first four weeks of study participation. Those participants who discontinued alcohol treatment during study weeks 1-4 were contacted by study staff and completed the questionnaire by telephone. However, blood pressure, pulse, exhaled carbon monoxide, and breath alcohol measurement were not measured in these participants.

Ninety four percent (94%) of participants completed all weekly screenings in person. At week 9 and 6 months, participants responded to the follow-up questionnaire via mail or telephone. At 6 months, collateral informants were contacted to confirm cigarette and alcohol use history provided by participant.

Adverse event information was collected and reviewed every four weeks throughout the study by study staff until the last enrolled participant completed the 6 month follow-up. Statistical MethodsData were analyzed with SPSS and SAS statistical packages. T-tests and chi-square tests were used to compare the baseline characteristics between the treatment groups. Fisher's exact test was used for comparisons for small sample situations and the Wilcoxon rank sum test was used for continuous data when normality assumptions were not met. An a priori sample size of 130 (65 in each group) was powered to detect a difference of medium size (.18). However, use of contraindicated medication and other factors noted above limited the number of prospective participants to 90.

Seventy-five percent of them were enrolled in the study. In order to help control the type I error rate due to testing multiple endpoints, p-values less than 0.01 will be considered statistically significant. When comparing the follow-up rates between the groups, the rates calculated account for the number of drop outs at each time point. In general, only data from participants who responded to the surveys were analyzed.

These are called “respondent” analyses. For the smoking cessation rates, we also did an “intention to treat” analysis, where non-responders are assumed to be smoking cigarettes. Sample CharacteristicsEighty-four percent of study participants were male. All females were enrolled from the community site. The bupropion and placebo groups were similar in gender, racial and ethnic composition, and age at study entry.

The mean number of cigarettes per day at study entry was 27 in the placebo group and 23 in the bupropion group. The mean Fagerstrom Test for Nicotine Dependence (FTND) was 6 in both groups.

Fifty-three percent of participants had at least one other substance dependence in addition to alcohol and nicotine. Drinking measures and mental health history were similar in the two groups. Two (7%) of the placebo group and four (13%) of the bupropion group were on antidepressants at study entry. Many of the study participants reported a history of mental illness, most commonly an affective disorder or anti-social personality disorder. Twenty-two percent of participants reported desire to quit smoking within the next 6 months and 78% reported wanting to quit within the next month.

Cigarette SmokingAt each follow-up point there was no significant difference in cigarette smoking outcomes between the placebo and bupropion groups. At week four there appeared to be a trend toward benefit with bupropion, however, by week 9 this trend was reversed and maintained through the remainder of the follow-up period in both the “intention to treat” and “respondents only” analyses. Interestingly, at weeks 4, 9 and 6 months there was a significant change (all P. AlcoholContinuous abstinence, drinks per day, drinks per drinking day and percent days abstinent in the previous 30 days were measured at each follow-up point. At week 4, the placebo group were more likely to be continuously abstinent from alcohol, had fewer drinks per day, and greater percent days abstinent in the previous 30 days but these were not statistically significant. When asked about continuous abstinence from alcohol since study entry, collateral contacts for 7 of 30 respondents who reported 30 days of continuous abstinence at 6 months reported at least a single episode of drinking several drinks since study entry. Also of note, participants who successfully discontinued smoking at 6 months reported greater continuous abstinence from alcohol, fewer drinks per day, and more abstinent days in the previous 30 days but, again, these differences were not statistically significant.

Compliance and TolerabilityThere was no significant difference in medication compliance between participants on bupropion and placebo weeks 1-4 however, at each week participants in the bupropion group reported taking fewer of the capsules than those on placebo. We attempted to assess medication compliance during weeks 5-9 by asking participants to return medication bottles (with any unused bupropion/placebo) and any unused nicotine patches with their week 9 follow-up questionnaires. However, the majority of participants did not comply with our request and we are unable to assess medication compliance for weeks 5-9.There were no seizures in the study population. The most common side effects reported with bupropion were insomnia and headache. Ten (33%) of the participants on bupropion reported discontinuing drug during weeks one through four while only three (11%) of participants on placebo reported discontinuing medication during the same time period (P=0.059).

Insomnia was reported by eleven of the participants in the bupropion SR group during weeks 1-4 but by only two participants in the placebo group. Effect of bupropion on cigarette and alcohol useTo our knowledge this is the first study evaluating the efficacy of bupropion for smoking cessation in alcoholics early in their alcoholism treatment. The primary outcome of this study indicates that bupropion, when added to nicotine patch therapy, did not improve smoking outcomes in this population of “in treatment” alcoholics. In this preliminary study, there was a trend toward poorer alcohol outcomes in three of the four alcohol outcomes measured at week four in the bupropion group.Given that bupropion has been been shown to be efficacious in multiple other populations, its lack of efficacy in early in treatment alcoholics may be associated with a feature unique to this population. It is possible that the side effects associated with bupropion may be less tolerable or more frequent in newly sober alcoholics prompting discontinuation of bupropion.

The current study is remarkable for the number of participants in the bupropion group who reported insomnia. By the end of week four, 33% of participants on bupropion had reported discontinuing the drug. In previous studies 6% , 11-12% , and 10% of participants discontinued bupropion due to side effects. Compliance with bupropion and placebo was not assessed weeks 5 – 9. It is possible that the side effects associated with bupropion prompted discontinuation of drug in weeks1-4 in one-third of participants and less compliance in the remaining subjects during the remaining 5 weeks of the study which went undetected. At week 4, participants on bupropion had better (but not significant) cigarette outcomes and worse alcohol outcomes. Early use of bupropion may have resulted in less cigarette use at week 4 but simultaneously contributed to increased alcohol use to combat insomnia.

Alcoholics typically report higher rates of insomnia (36% - 67%) than the general population (17%-30%) with 60% - 70% reporting using alcohol to assist with sleep. Insomnia in alcoholics has been associated with relapse to alcohol. In clinical practice, a patient's report of insomnia while on bupropion dosed twice daily would likely result in a dosage or schedule change. The study protocol did not allow for such an adjustment and it is conceivable that a modifed dosage or schedule may have been more tolerable in this population. Effect of Nicotine replacement on cigarette use in alcoholicsParticipants in this study, all of whom utilized nicotine patch with or without bupropion, showed a significant reduction in cigarette smoking at each follow-up point. Study participants reported a decrease from a median of 20 cigarettes per day at baseline to 4.8 cigarettes per day at 6 months. There was a significant change from baseline in the median number of cigarettes smoked in both the placebo and bupropion groups at weeks 4, 9 and month 6 (all p.

Relationship between smoking cessation and alcohol sobrietyIn our study, 75% of respondents reported continuous alcohol abstinence in the previous 30 days at 6 months. These findings are similar to those seen by Joseph at 6 months in alcoholics who were treated for cigarette smoking concurrent to their alcohol treatment (67%) or in those treated six months later (74%). While our findings, given the modest number of subjects, must be considered preliminary, we found no evidence that those who were successful at smoking cessation in this study jeopardized their sobriety from alcohol. Those who quit cigarettes had better alcohol outcomes at six months in three of four alcohol outcome measures supporting earlier studies which reported improved drug or alcohol outcomes in persons who discontinued cigarettes (;; ). Participants who discontinued cigarettes reported no non-alcohol drug use at six months. Affective and Anti-Social Personality DisorderTo our knowledge this is the first study to examine smoking quit rates in persons undergoing treatment for alcoholism with a history of affective disorder or with antisocial personality disorder (ASPD). Smoking cessation outcomes were similar in the affected and non-affected groups.

While eligibility criteria excluded persons with currently symptomatic depression and any diagnosis of bipolar affective disorder, smoking outcomes were similar in those participants who reported a history of or symptoms suggestive of depression or mood instability as those who did not. Likewise, the Mean Beck Depression Inventory score was similar in those who were and were not abstinent from cigarettes at six months. Similarly, persons with and without antisocial personality disorder had comparable outcomes. Clearly alcoholics with ASPD or stable depressive disorders may be candidates for a cigarette quit attempt.

Persons with cooccurring disorders (mood disorder + alcoholism or ASPD + alcoholism) are reported to have poorer SUD outcomes but, in this setting, had quit rates similar to those without the dual disorder. Strengths and weaknessesThis study of in treatment alcoholics has a number of strengths. Alcoholics who are recently symptomatic are typically excluded from cigarette cessation studies. This is the first study of bupropion in alcoholics undergoing alcoholism treatment. Participants were recruited in a naturalistic fashion within one week of entry into multiple levels of care (residential, intensive outpatient or low intensity outpatient alcohol treatment) in a community and VA setting. They were heavy smokers and the majority had made multiple alcohol and cigarette quit attempts.

Other drug use or treatment with many frequently prescribed anti-depressants did not preclude study enrollment. Persons with stable depression, anxiety, post traumatic stress disorder and anti-social personality disorder participated in the study. All participants were given an 8 week course of nicotine patch and encouraged to attend a one hour education and group session and continued with alcohol treatment as usual. The population studied is typical for many community and VA based treatment settings. Alcohol and cigarette outcomes were measured at six months.There are several factors which contribute to the limitations of this study.

Given the modest number of participants in this study, the findings discussed above must be considered preliminary. Secondly, we did not confirm participant reports of alcohol or cigarette use/abstinence bio-chemically and relied on self-report and the information provided by collaterals (in some cases the two collateral contacts disagreed with each other).While this practice is consistent with many previous smoking cessation studies, it does contribute to a lack of confidence about our findings. We were not reliably able to ascertain compliance with either the nicotine replacement product or bupropion/placebo capsules weeks 5-9 of the study which may have diluted any differences between the intervention and control groups. Given the apparent robust response to nicotine patch treatment in all participants and the size of the study population, a small difference in the two study groups would be difficult to detect. Participants were recruited from two publicly funded sites which largely serve low income alcoholics. Additionally, we did not enroll persons with a history of alcohol withdrawal seizures.

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The primary purpose of this study is to determine whether, among smokers with elevated depressive symptoms, sequential antidepressant pharmacotherapy with fluoxetine (20 mg) begun 8 weeks prior to and extended throughout standard smoking cessation treatment with transdermal nicotine patch (ST-TNP) will result in superior short-and long-term smoking cessation outcomes compared to sequential pharmacotherapy with placebo medication combined with ST-TNP. The secondary aim of the study is to test the hypothesis that, among smokers with elevated depressive symptoms, sequential treatment with fluoxetine will result in lower levels of depressive symptoms and negative mood and higher levels of positive mood immediately prior to and throughout the course of smoking cessation treatment relative to the placebo condition.

Condition or diseaseIntervention/treatmentPhaseMajor Depressive Disorder Nicotine Dependence DepressionDrug: Fluoxetine Drug: DextrosePhase 3. Cigarette smoking is the leading cause of death and disability in the United States, accounting for over 430,000 deaths in this country every year.

The selection hypothesis of smoking prevalence argues that smokers who are unable to quit successfully are likely to possess risk factors or characteristics that make it difficult to quit, such as nicotine dependence and psychiatric comorbidity. As such, significant strides in helping 'today's' smokers quit will ultimately be found in the ability to develop specialized treatments that target the particular needs of subgroups of smokers, especially those who are at higher risk for relapse. Depression is the psychiatric disorder most frequently associated with cigarette smoking in adults and strong associations have been demonstrated between cigarette smoking and both depressive disorders and depressive symptoms. In fact, a prospective analysis from the National Health and Nutrition Examination Survey showed that smokers with elevated depressive symptoms were 40% less likely than nondepressed smokers to have quit nine years later.The development of an efficacious, specialized treatment of nicotine dependence for smokers with elevated depressive symptoms would address this need by providing physicians with an effective treatment alternative for the large number of smokers with depressive symptoms seen daily in clinical practice.

This study examines the hypothesis that smokers with elevated depressive symptoms treated with fluoxetine 8 weeks prior to quitting and extended throughout 8 weeks of standard treatment with the nicotine patch post-quit will demonstrate superior cessation outcomes compared to placebo medication combined with standard treatment and the nicotine patch, administered with the identical treatment schedule. A secondary hypothesis is to examine whether reductions in depressive symptoms and negative mood and increases in positive mood will be greater for those in the sequential fluoxetine versus placebo condition. Layout table for MeSH termsTobacco Use DisorderDepressionDepressive DisorderDepressive Disorder, MajorBehavioral SymptomsMood DisordersMental DisordersSubstance-Related DisordersChemically-Induced DisordersFluoxetineSerotonin Uptake InhibitorsNeurotransmitter Uptake InhibitorsMembrane Transport ModulatorsMolecular Mechanisms of Pharmacological ActionNeurotransmitter AgentsSerotonin AgentsPhysiological Effects of DrugsAntidepressive Agents, Second-GenerationAntidepressive AgentsPsychotropic DrugsCytochrome P-450 CYP2D6 InhibitorsCytochrome P-450 Enzyme InhibitorsEnzyme Inhibitors.