Use of varenicline in smoking cessation: two case reports

Abstracts

O objetivo deste trabalho foi antecipar informações sobre uma droga que está sendo lançada no combate ao tabagismo, auxiliando aqueles que desejam parar de fumar. O varenicline atua no sistema nervoso central, ligando-se ao receptor nicotínico alfa4beta2 e proporcionando redução do prazer que o cigarro provoca. É um mecanismo de ação novo, que nenhum psicofármaco atinge. Os estudos têm mostrado superioridade do varenicline em manter taxas mais altas e prolongadas de abstinência, quando comparado à bupropiona e placebo. Caso 1: Homem, 51 anos, mais de 30 anos de tabagismo. Nunca atingiu abstinência superior a algumas semanas. Utilizou varenicline na dose preconizada e, na 12ª semana, quando podia interromper, resolveu manter o fármaco até completar 24 semanas de tratamento. Está abstinente há 8 meses. Caso 2 Mulher, 48 anos, 30 anos de dependência do tabaco. Há 21 anos, parou espontaneamente na gestação da única filha e, após 6 meses, recaiu. Usou varenicline por 12 semanas associado à terapia cognitivo-comportamental. Há 7 meses, está abstinente. Os tratamentos disponíveis até o momento são incipientes em promover altos índices de abstinência no primeiro ano. Portanto, a abordagem engloba um conjunto de estratégias, como disponibilizar drogas de primeira linha, além de medidas e projetos que apóiem não só o parar de fumar, mas o continuar abstinente. O tratamento do tabagismo requer investimento público; do contrário, drogas como o varenicline vão beneficiar apenas uma pequena parcela da população.

Varenicline; tratamento; tabaco; cigarro

CASE REPORT

Use of varenicline in smoking cessation: two case reports

Fabiano Coelho Horimoto^I; Mariele Bevilaqua^II

^IProfessor, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS, Brazil

^IIMedical student, Universidade Federal de Santa Maria (UFSM), Santa Maria, RS, Brazil. This study was carried out at Psychiatry Service, Faculdade de Medicina, UFMS

^{Correspondence}

ABSTRACT

The objective of this study was to provide information about a new drug to help people quit smoking. Varenicline acts on the central nervous system and binds to the alpha4beta2 nicotine receptor, reducing the sensation of pleasure caused by smoking. Its mechanism of action is unique, different from any other psychotropic. Studies have shown that, when compared with bupropion and placebo, varenicline is more effective in maintaining smoking abstinence and for longer periods of time. Case 1: A 51-year-old male patient who has been smoking for more than 30 years. He has never been more than a few weeks without smoking. He used the recommended dose of varenicline and, although he could have stopped after 12 weeks, preferred to follow the treatment for 24 weeks. He has been abstinent for 8 months. Case 2: 48-year-old female who has been tobacco dependent for 30 years. She quit during the pregnancy of her daughter 21 years ago, but started again 6 months later. She used varenicline for 12 weeks associated with cognitive-behavioral therapy. She has been abstinent for 7 months. Currently available treatments still have limited effectiveness in assuring high abstinence rates over the first year. Therefore, our approach includes several strategies, such as administration of first-line drugs, besides measures and projects that not only help patients quit smoking, but also remain abstinent. Anti-smoking treatments require large investments from the government. Otherwise, new drugs, such as varenicline, will only benefit a few segments of the population.

Keywords: Varenicline, treatment, tobacco, cigarette.

Introduction

Smoking is currently the most serious public health problem faced by most countries, due to its confirmed effects on occurrence and worsening of many diseases. According to the World Health Organization,¹ smoking accounts for 4.9 million deaths a year.

Based on data from 1988² published by the American Health Ministry Report, costs related to diseases caused by tobacco amounted to US$ 1 billion a day. In Brazil,¹ around 200,000 people currently die every year due to diseases directly related to smoking. Therefore, besides being an extremely lethal dependence, smoking practically reaches the whole world, exposing every government to a confrontation of this problem. For taking millions of lives annually, it is considered the greatest independent avoidable cause of early deaths. As Silva³ states, tobacco is, along with alcohol, the social drug par excellence of modern world.

According to Frances & Franklin Jr.,⁴ alcohol and tobacco are still the most widely used and abused substance, and those that bring more risk to health. It is also remarkable the use of tobacco by special populations, such as mental patients. Cigarettes reduce the plasma level of many drugs, such as antipsychotics and antidepressants, due to induction of liver enzymes that metabolize them.⁵

Data from the American Ministry of Health Report² indicate that, in psychiatry, up to 50% of outpatient depressed individuals smoke, besides 70% of bipolar patients and 90% of schizophrenics. In a survey of psychiatric patients in São Paulo, Brazil, Ratto et al.⁶ observed the same prevalence increase in that population. Therefore, psychiatrists stand in a unique condition to approach this population and encourage them to stop smoking.

Case report

Case 1

A 51-year-old male patient, in his second marriage, born in Rio Grande do Sul and resident in Campo Grande. The patient has smoked since he was 16, when he already reported consumption of 20 cigarettes a day. His first attempt of cessation was about 2 years ago, and was abstinent for around 40 days, with the support of a multiprofessional team in Porto Alegre. His physician at that time diagnosed a bipolar affective disorder associated with abusive alcohol consumption. In March 2006, back to Campo Grande, he was hospitalized in a clinic for 1 week, but started smoking at the same day he was discharged. Dependence level according to Fagerström Score:⁷ high (6 points).

The patient and his wife sought psychiatric care 11 months ago and, due to a lack of control of alcohol consumption, he was once again hospitalized at the previous hospital. During his visits to the psychiatrist, he was explained about the possibility of using varenicline, and was receptive to using this new drug. His main motivation at that time was a pulmonary impairment, since he had already started an emphysematous process.

At hospital discharge 10 days later, he was taking oxcarbazepine 900 mg, escitalopram 20 mg, alprazolam 1 mg and disulfiram 250 mg. At the same week, he ordered the medication and, in the beginning of September 2006, had the same therapeutic scheme for 12 weeks, following the directions for taking it.⁸ He had no recurrences, was judiciously inspected as to alcohol and tobacco consumption by his wife, who administered the drugs. There were no adverse effects. In December, the patient decided to continue varenicline, after the first 12 weeks. After completing 24 weeks of use, a gradual removal was scheduled in 1 week, on patient's request. He has been abstinent for 8 months and stopped varenicline 2 months ago. He feels much better in terms of general and respiratory status.

Case 2

A 48-year-old female patient, divorced, born in Santa Catarina and resident in Campo Grande. She has been a smoker "since adolescence," does not remember when exactly she started smoking, but when she was in college (she entered at the age of 18) she already smoked one pack a day. At 30, she stopped smoking during the pregnancy of her only son, without specific treatment, and resumed smoking around 6 months after giving birth. Since then, she has made unsuccessful and occasional attempts of cessation, which did not last more than a few weeks. Due to her partner's insistence, a non-smoker, she recently tried to stop smoking by using nicotine patches associated with bupropion 300 mg a day, but was abstinent for 3 weeks, attributing such recurrence to a "desire of feeling the pleasure of smoking once again." Dependence level according to Fagerström Score:⁷ very high (eight points).

In October 2006, she started taking varenicline 0.5 mg once a day, doubling the dose after 7 days, when she stopped smoking. She felt mouth dryness during the first days. Three months ago, she interrupted the medication due to its high cost, completing 12 weeks of continuous use of 1 mg (dose recommended by the laboratory is 2 mg from the eighth day until 12 weeks) and, since then she has been abstinent, and does not feel any desire or compulsion to smoke. Concomitantly, she is undergoing cognitive-behavioral therapy for around 9 months and feels that such approach has been very useful for the treatment.

Discussion

Current pharmacological treatments usually follow different mechanisms of action in the central nervous system, causing some changes that can be positive in the abstinent individual, reducing desire to smoke, such as some antidepressants, or mimicking the effect of nicotine itself, such as in patches and gums.⁹ All therapies offered deal with extremely disappointing medium-term abstinence rates (6 months).

The most widely used drugs are:

a) Bupropion:¹⁰ it is a prodopaminergic drug that acts on the brain's reward circuit due to acute dopamine release into nucleo accumbens, responsible for the pleasant effect offered by cigarettes. However, tobacco has an acute and much more powerful action as a dopamine releaser, and such effect is minimal by bupropion.

b) Nortriptyline:¹¹ less used, studies indicate a 6-month abstinence in 20% of patients who used it vs. 5% in the placebo group. It is considered a second-line drug, but cost-effective. It does not have a specific mechanism of action favoring this treatment; those who support this therapeutic approach claim that mood and anxiety modulation and reduction in irritability provided by this drug in many abstinent individuals can avoid early recurrences. But not all individuals will benefit from this conduct or feel its effects.

c) Nicotine replacement therapy (NRT) associated with cognitive-behavioral therapy (CBT): this association can be useful in many cases. According to Gilbert & Warburton, apud Pedroso et al.,¹² by adding the non-pharmacological approach, there is the possibility of encouraging permanent changes, such as smoking cessation. With regard to NRT, many studies^13,14 have observed a higher efficacy in reduction of number of cigarettes compared with total abstinence. We know that reduction in risks for diseases related to smoking is minimal or inexistent in individuals who reduce the total amount of daily cigarettes, but keep smoking.

With the advent of varenicline, launched this year, a drug was finally obtained that can act to provide higher probabilities of efficacy in promoting higher and longer rates of abstinence. This psychotropic acts as a partial antagonist of nicotine receptor alpha4beta2,¹⁵ which is responsible for the desire of smoking, anxiety and craving, whereas its antagonism causes reduction in the pleasure of smoking.

A meta-analysis by Wu et al.,¹⁶ including 70 articles reporting the results of placebo-controlled studies, indicated superiority of varenicline compared with bupropion, nicotine replacement therapy and placebo over a 1-year period. Nides et al.¹⁷ observed abstinence rates of 48% in 4 weeks in the group taking varenicline 2 mg and 37% in the group taking 1 mg vs. 17% in those taking placebo.

In longer follow-ups, such as that performed by Oncken et al.,¹⁸ reduced efficacy is expected, but even so 22.4% of patients in this study taking varenicline 1 mg were abstinent, vs. 18.5% taking 0.5 mg and 3.9% taking placebo.

In both cases, the patients clearly reported a marked reduction in desire of smoking, in comparison to other attempts they had made. Despite the short abstinence period (8 and 7 months, respectively), the result of these reports is promising to encourage physicians and patients to consider this treatment as a really efficacious method for many patients.

Therefore, new drugs that can increase the therapeutic options in the treatment of smoking are valuable and indispensable measures to face this serious problem, and we hope that, in a near future, the rate of smokers can be significantly reduced.

References

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15. Coe JW, Brooks PR, Veteline MG, Wirtiz WO, O'Neill BT, Sands SB. Varenicline (CP-526,555): a novel, potent and selective nicotinic receptor partial agonist for the treatment of smoking cessation. In: Colby SM, Drobes DJ, West R, eds. Proceedings of the SRNT's 11th Annual Metting and 7th Annual European Conference. Praga, Rep Tcheca; 2005. Nicotine Tob Res. 2005;7(4):667-709.

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18. Oncken C, Gonzales D, Nides M, Rennard S, Watsky E, Billing CB, et al. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Arch Intern Med. 2006;166(15):1571-7.

Received April 30, 2007

Accepted July 21, 2007

Publication Dates

• Publication in this collection
  13 Dec 2007
• Date of issue
  Aug 2007

History

• Accepted
  21 Aug 2007
• Received
  30 Apr 2007