PHD THESIS STUDY ON THE USE OF THE PHARMACOLOGIC THERAPY WITH BUPROPION ON TOBACCO ABSTINENCE FOR SMOKERS WITH HIGH NICOTINE DEPENDENCE
THE GENERAL PART……………………………………………………. . ……. . . . . . . . .…….2
THE SPECIAL PART………………………………………………………………. . . . . . . . . ….2
MOTIVATION FOR CHOOSING THE THEME…………………. . . . . . . . . . . . . . .…2
THE PURPOSE FOR RESEARCH………………………………………………. . . . . . . . ……3
MATERIAL AND METHOD………………………………………………………. . . . . . . . .…. 3
OBJECTIVES………………………………………………………………………. . . . . . . . . . . 4
RESULTS………………………………………………………………………….…. . . . . . . . . …. 4
DISCUSSION………………………………………………………………………. . . . . . . . . …. .…6
CONCLUSIONS……………………………………………………………………. . . . . . . . . .…. 8
PROPOSALS…………………………………………………………………………. . . . . . . . . .10
CURRICULUM VITAE…………………………………………………….…. . . . . . . ……. . ….11
THE GENERAL PART In Chapter I are inserted data on smoking, nicotine addiction, withdrawal syndrome,
recurrence, smoking cessation, economic tobacco threat and general aspects of chronic
Chapter II describes data on the epidemiology, prevalence of smoking, mortality
caused by smoking, health benefits after giving up smoking, factors associated with quitting
smoking, variability of cessation in different countries and the potential of giving up smoking
to reduce future deaths due to tobacco. Chapter III contains information about the psychopharmacology of tobacco
dependence, the neurobiology underlying nicotine addiction, the nicotine test and diseases
Chapter IV shows the types of intervention and treatment methods for smoking
cessation, pharmacological intervention, types of intervention, specialized counselling and
Chapter V describes data on pharmacotherapy and nicotine replacement therapy. Chapter VI includes treatment with bupropion, and other pharmacological methods,
treatment with varenicline, general data. Chapter VII THE SPECIAL PART MOTIVATION FOR CHOOSING THE THEME
In this paper we propose the research of bupropion administration in pharmacological
therapy of tobacco withdrawal in smokers with a high degree of nicotine dependence in terms
of unfolding the National Program to promote health and health education of the Ministry of
Health in the prevention and control of tobacco for Valcea County. Bupropion therapy - the first non-nicotinic treatment - in terms of national program in
Valcea County, we considered it important as there was no study on pharmacological therapy
on tobacco withdrawal in smokers with high nicotine dependence and any other information
relating to the prevention and combating tobacco consumption in Valcea County.
For Valcea County, the program STOP SMOKING started in July 2008 in the second
stage of the National Program. The establishment of the STOP SMOKING cabinet in Valcea
County was held at the Pneumatology hospital “Constantin Anastasatu" in Mihaiesti after the
training courses conducted in December 2007 at the Institute of Pneumatology Marius Nasta -
Bucharest in the training program for physicians included in the National Program for
prevention and control of tobacco consumption. In Valcea county there was no assistance
cabinet in preventing and combating tobacco consumption until July 2008.
The establishment of the STOP SMOKING cabinet at the Pneumatology Hospital
“Constantin Anastasatu” - Mihaiesti involved:
1) ensuring appropriate therapy medication (bupropion, varenicline, nicorette patches)
and the metering device for carbon monoxide.
Before starting the program STOP SMOKING in Valcea County in the program
conditions, there was a small group of patients, 38 in number; in the bupropion therapy could
not be evaluated, as there is no necessary material base. THE PURPOSE FOR RESEARCH
Were investigated issues on the program STOP SMOKING at the Pneumatology
Hospital “Constantin Anastasatu” - Mihaiesti from Valcea County regarding pharmacological
therapy with bupropion in smokers with a high degree of dependence on nicotine in
The results obtained in therapy with varenicline in smokers with high nicotine
dependence were seen and identifying opportunities harnessed to some categories of smokers
The study was a prospective longitudinal study. When the varenicline therapy was
available, we proceeded to the randomized case, the file encoding and decoding at the end of
The blind randomized study - the operation being performed by a third party. The
author taking knowledge of the type of treatment that returned to each subject only at the end
MATERIAL AND METHOD
Were used the data in the consulting registry of the smoking cessation office from the
Pneumatology Hospital “Constantin Anastasatu” - Mihaiesti, Valcea County, and the
evaluation of the dependence was done by the Fagerström test; the subjects were respondents
is compiling a smoker’s observation sheet - initial - and the observation control sheets and
at the end of the program the smoker’s observation sheet - final evaluation.
They studied a total of 918 smokers divided into 2 groups:
- A group of 752 patients in therapy with bupropion
- A group of 115 patients in therapy with varenicline
THE SMOKER’S INITIAL, CONTROL ANF FINAL OBSERVATION SHEET
Subjects were questioned to submission to the Cabinet STOP SMOKING from the
Hospital “Constantin Anastasatu"- Mihaiesti preparing the initial observation sheet, the
control observation sheet at 2 to 4 weeks and final to 3 months. OBJECTIVES
1. The study of results on pharmacological therapy with bupropion on abstinence from
tobacco in smokers with high nicotine dependence in conditions of the National Program
and in comparison with the results obtained with varenicline.
2. Analysis of the most important reasons for smoking cessation in subjects who received
therapy with bupropion or varenicline, highly dependent smokers.
3. Analysis of demographic factors in smokers enrolled in the Valcea STOP SMOKING
program during July 2008-July 2009 in therapy with bupropion or varenicline.
4. Withdrawal rate analysis of varenicline versus bupropion therapy in categories of
smokers in the STOP SMOKING program recorded in the county of Valcea.
5. The daily cost of smoking to smokers with high nicotine dependence.
6. Tobacco consumption and nicotine dependence score in subjects included in the study
7. Adverse reactions to therapy with bupropion and varenicline. Chapter VIII Group distribution according to gender
The analysis of the entire batch includes 918 subjects in pharmacological therapy.
Distribution by gender showed a total of 301 women representing a rate of 32.79% and 617
The distribution by gender in the group that received treatment with bupropion
(Zyban) showed the following distribution:
- 518 males, representing a rate of 68.88%
- 234 females representing a percentage of 31.12%
The analysis of gender distribution of the group that received treatment with bupropion
respects the world-wide gender distribution and the dynamic of tobacco consumption among
The structure on gender of the group in therapy with varenicline (Champix) showed a
total of 46 women representing 40% and a total of 69 men representing 60%.
The analysis of gender distribution in the group with varenicline therapy respects
increased prevalence for smoking in men than in women in the population of our country. Environment of origin:
Distribution of the group according to the environment of origin shows the following:
- Rural113, representing a rate of 12.30%
- Urban 805, representing a percentage of 88%
Distribution of the group in therapy with bupropion shows:
Distribution of the group with varenicline shows: Distribution of the group depending on the final status The analysis of the entire batch depending on the final status shows: - Abstinents 424 subjects - Smokers 318 subjects - Lost 176 subjects
Distribution of the whole group depending on the final status in percentages shows the
- abstinents 46.19% - smokers 34.64% - lost 19.17%
Analysis of the distribution group with bupropion according to the final status shows the
- Abstinents 345 subjects - Smokers 263 subjects - Lost 144 subjects
In percentage the distribution group with bupropion shows the following:
- Abstinents 45.8% - Smokers 34.97% - Lost 19.15%
The analysis of the distribution group with varenicline according to the final status shows the
- Abstinents 59 subjects - Smokers 37 subjects - Lost 19 subjects
The analysis of the distribution group with varenicline according to the final status in
- abstinents 51.30% - smokers 32.17% - lost 16.52% Comparing the final results of the two groups a lot in addition to abstinent smokers in
varenicline therapy stands out as follows:
- 59 abstinents representing 51.30% in varenicline therapy
- 345 abstinents representing 45.88% in bupropion therapy Smokers:
- 263 representing 34.97% in bupropion therapy
- 37 representing 32.17% in varenicline therapy
Lost:
- 144 representing 19.15% in bupropion therapy
- 19 representing 16.52% in varenicline therapy
Chapter IX DISCUSSION
The analysis of demographic factors in smokers enrolled in Valcea County STOP
SMOKING program during July 2008 - July 2009 in therapy with bupropion or varenicline.
From the analysis of the entire group of 918 subjects in total, the distribution according
- Men 617representing 67.21% - Women 301 representing 32.79%
Comparing the gender division of the entire group based on gender division of the
National Program STOP SMOKING, there is a higher percentage of women in the national
group making a percentage of 45.2% from 32.79% in the study group. In males, the
proportion of the national group is 54.73% against 67.21% in the study group.
High rates of tobacco consumption in our country are largely made on account of higher
frequency of smoking among women and youth in general. Growth was evident in women:
11.3% of women aged over 15 years in 1989, 15.2% in 1994 and 25% in 2000. Teenagers
showed the same issue that 21% of the adult population of Romania were already smoking
daily at 15 years of age. (National Statistics Institute, 2001).
Comparing the reasons for cessation, the national group finds a high prevalence of
motivation represented by health (59.9%), followed by the financial motivation (18.1)%,
The motivation "I had enough" is found in 3% of subjects, much lower than the same
The motivation for quitting smoking was most frequently related to health, but also the
financial burden (especially in the context of recent higher prices of cigarettes) and pressure at
work (the law on banning smoking in public places and institutions). (Didilescu C., 2009).
In the therapy group with bupropion the statistics show the following:
- A peak prevalence for the motivation "I had enough" followed by financial reasons,
fear of illness, desire to no longer be dependent, partner pressure and pre-existing disease.
In the therapy group with varenicline the main motivation was fear of illness, followed
by financial reasons, desire to no longer be dependent, partner pressure and "I had enough."
From the statistic analysis for the final status for the two groups we consider that:
The national results of the clinical experience in the National Program STOP
It found a higher proportion of abstinents in the two groups studied. The proportion of
smokers is about equal in Valcea and national experience, and the proportion of lost patients
The analysis shows a high prevalence of subjects lost approximately 20% in study
groups and 34% in the nationwide group.
The ratio of smokers and those lost in the groups achieved show a rate of 53.81% from
According to bupropion therapy outcomes in the study group, the success rate is above
The rate of lost subjects in group therapy with bupropion is below the national lost
subjects’ rate in 2007 and close to the nationwide lost subjects’ rate in 2008, 19.5% from
Available in Romania since 2000, the drug has been used successfully on the Romanian
market and because of the advantage to be the only option available of pharmacological
treatment for tobacco abstinence between 2001-2007.
Bupropion works by amending some of the nicotine abstinence symptoms, including
depression in particular, reducing the overall severity of withdrawal syndrome, which we
recommend as an unquestionable aid in the smoking cessation process.
Administration of bupropion in smokers with severe addiction significantly reduces
depressive symptoms associated to withdrawal. Bupropion doubles abstinence rates compared
to placebo and has similar effect in both sexes. Chapter X CONCLUSIONS
1. Bupropion is the first non-nicotinic treatment used for smoking cessation.
Of bupropion therapy study group represented in 752 patients was obtained a rate of
abstinence greater than the abstinence rate at national level, representing 45.88%.
2. For the 115 patients in the therapy group with varenicline was obtained a rate of 51.30%
abstinence rate greater than the national rate.
3. Abstinence rates are similar to rates in clinical trials.
4. In the therapy group with bupropion was recorded a fairly large percentage of lost
5. The percentage of smokers is about 34.97% for bupropion and 32.17% for varenicline
6. The remaining subjects smoking rate still remains quite high and can be reduced through
better monitoring and increased treatment duration.
7. The rate of lost subjects achieved a fairly significant percentage of 19.15% for bupropion
and 16.55% for varenicline being placed under the national rates. High percentage of lost
subjects requires more effort from the staff involved in counselling and therapy to
8. There is no statistically significant difference between the two groups related to therapy
9. Bupropion significantly reduces withdrawal symptoms and the desire to smoke.
Bupropion has a well established safety profit and reduces the urge to smoke.
10. Bupropion causes significant reduction in symptoms of deprivation. (anxiety, difficulty in
concentrating, restlessness, irritability, frustration and anger).
11. Treatment with bupropion is effective, the success rate approaching 50%
12. Motivation for quitting smoking was most often related to fear of disease and financial
reasons for both the group in therapy with bupropion and the group in therapy with
13. From the analysis of demographic factors the patients were more frequently men than
women, from the urban environment, married with children, age groups with high
prevalence between 30-39 years, 40-49 years, 50-59 years and 20-29 years old.
There was no statistical difference between the average age of the subjects in the therapy
group with bupropion and the average age of subjects in the therapy group with
14. The daily cost analysis showed a cost between 6-10 RON from 676 subjects representing
73.64% followed by a group of 175 subjects with a cost between 11-15 RON representing
There is no significant difference for the subjects in the bupropion group and subjects in
the varenicline group on the average daily cost.
15. The tobacco consumption defined by the number of package-year showed a disposition
of subjects to a consumption higher than 20 packages-year, most subjects being part of
There is no statistically significant difference between the package-year average of the
group with bupropion and the group therapy with varenicline therapy.
16. The score of nicotine dependence determined by the Fagerström test allowed the
assessment of nicotine addiction severity in most subjects achieving 7, 8, 9, and 10 points
in the Fagerström test, the addiction being severe.
17. The most common adverse reactions were:
➢ For bupropion: insomnia, headache, dry mouth;
➢ For varenicline: nausea, insomnia, headache and abnormal dreams. Chapter XI PROPOSALS
Three key components of treatment should be part of every clinical intervention:
Counselling; Drug therapy; Change in the system that result in institutionalization of tobacco dependence treatments;
Counselling provided individually, in groups, or online via phone lines is effective.
While short-term counselling is effective, a more intensive counselling results in
clearly higher rates of smoking cessation. Drug therapy for treating tobacco addiction, including nicotine replacement
medications (e.g. patch, gum, nasal spray, inhaler, sublingual tablets, and aromatic pills),
bupropion and varenicline have shown to be effective. On average, these medications double
an individual's chances of obtaining a long-term abstinence.
In order to support smokers in Romania, limiting tobacco epidemic and preventing
tobacco-related deaths we consider the following policies mandatory:
• Monitoring tobacco use and prevention policies • Protecting people against tobacco smoke • Providing assistance to quit smoking • Supporting the ban on tobacco advertising, promotion and sponsorship. • Tobacco tax increases. CURRICULUM VITAE
3. Date and place of birth: 02 November, 1957, Spineni Commune, Olt County
1978 -1984 The Faculty of General Medicine Craiova 1984 - General Medical Practitioner, Ramnicu Valcea County Hospital 1984 -1987 - junior doctor at the Sanitary Department Valcea 1987 - general medicine physician medical services Malaia, Valcea 1988 -1991 - secondary physician at the Institute of Pneumatology "Marius Nasta",
1992 - Specialist in Pneumatology at the Hospital „Constantin Anastasatu "- Mihaiesti,
01.03.1997 - Senior Pneumatology at the Hospital „Constantin Anastasatu" -
7. Skills: bronchology, functional exploration, general ultrasound
8. Master in "Health Service Management"
9. Member of the professional associations:
11. Currently: MD, Head of Department at the Hospital „Constantin Anastasatu" Mihaiesti,