The main goals of treatment of chronic obstructive pulmonary disease (COPD) are to relieve symptoms, reduce the frequency and severity of exacerbations, prevent disease progression, and reduce mortality. GOLD (Global Initiative for Chronic Obstructive Lung Disease) guidelines for treatment of COPD were updated recently. Treatment of acute exacerbations is not discussed here. Drugs available for treatment of COPD are listed in Tables 1 and 3.

Our December 11, 2023 article on Drugs for Depression included a single sentence on the safety of bupropion use during pregnancy: "The safety of bupropion during pregnancy has not been established; data from a bupropion pregnancy registry suggested a possible increase in cardiac malformations." A reader asked us to provide more information.

The FDA has approved an extended-release fixed-dose combination of dextromethorphan and bupropion (Auvelity – Axsome) for treatment of major depressive disorder (MDD) in adults.

The main goals of treatment for chronic obstructive pulmonary disease (COPD) are to relieve symptoms, reduce the frequency and severity of exacerbations, and prevent disease progression. Several guidelines and review articles on COPD treatment have been published in recent years. Treatment of acute exacerbations is not discussed here.

Smoking tobacco remains the primary preventable cause of death in the US. Smoking cessation often requires both pharmacotherapy and behavioral support.

View the Expanded Table: Some Drugs for Smoking Cessation

The main goals of treatment for chronic obstructive pulmonary disease (COPD) are to relieve symptoms, reduce the frequency and severity of exacerbations, and prevent disease progression. Updated guidelines for treatment of COPD have been published in recent years.

Tobacco dependence remains the primary preventable cause of death in the United States. It is a chronic disorder that often requires pharmacologic therapy, but counseling may be equally effective and can add to the effectiveness of any treatment for this indication. Abrupt cessation of smoking appears to be as effective as gradual reduction.

The FDA has approved a fixed-dose combination of the opioid receptor antagonist naltrexone (ReVia, and others) and the antidepressant and smoking cessation agent bupropion (Wellbutrin SR, Zyban, and others), as Contrave (Orexigen/Takeda) for weight loss. The combination was approved for use as an adjunct to diet and increased physical activity in patients with a body mass index (BMI) ≥30 kg/m² or a BMI ≥27 kg/m² and one or more weight-related comorbidities such as hypertension, diabetes, or dyslipidemia. Naltrexone/bupropion is not a controlled substance.

Electronic cigarettes, also called e-cigarettes, are advertised as a safer, more convenient, and socially acceptable alternative to smoking tobacco cigarettes. Widely available in retail stores and on the Internet, their use has been increasing over recent years, primarily among smokers, but also among non-smokers.

INHALATION DEVICES — Metered-dose inhalers (MDIs) require coordination of inhalation with hand-actuation of the device. Valved holding chambers (VHCs) or spacers help some patients, especially young children and the elderly, use MDIs effectively. VHCs have one-way valves that prevent the patient from exhaling into the device, minimizing the need for coordinated actuation and inhalation. Spacers are tubes or chambers placed between the canister and a face mask or mouthpiece, which also avoids the need to coordinate actuation and inhalation. Both VHCs and spacers retain the larger particles emitted from the MDI, decreasing their deposition in the oropharynx and leading to a higher proportion of small respirable particles being inhaled.

Electronic cigarettes, also called e-cigarettes, are battery-operated nicotine-delivery devices that resemble tobacco cigarettes. They deliver vapor containing a mixture of nicotine and either propylene glycol or glycerol. E-cigarettes are widely available in retail stores and on the internet in labeled strengths ranging from zero to high levels of nicotine and in flavors such as tobacco, mint, coffee, cherry, bubblegum, and chocolate. They are advertised as a healthier alternative to smoking a tobacco cigarette and, although not FDA-approved, as a smoking cessation tool.

Varenicline (Chantix), which has been associated with neuropsychiatric symptoms such as agitation, depressed mood, changes in behavior and suicidal ideation, appears to be the most effective drug available for treatment of tobacco dependence.1 Recently, the FDA warned that varenicline may also increase the risk of cardiovascular adverse events in patients with cardiovascular disease.2 This warning was based on the results of a 12-week randomized trial in 714 smokers with stable cardiovascular disease. The drug was effective in helping patients stop smoking; long-term quit rates (at 52 weeks) were 19% with varenicline and 7% with placebo.3 The results also included the following cardiovascular adverse events:

The authors of the study interpreted these results as providing reassurance that varenicline appears to be safe for use in smokers with stable cardiovascular disease. The FDA interpreted them as an association with a small increased risk of cardiovascular events if varenicline is used in patients with stable cardiovascular disease, and required the manufacturer to add this information to the labeling of the drug.

After the FDA's decision, a meta-analysis of 14 clinical trials in a total of 8216 patients with or without heart disease found that serious cardiovascular events occurred in 52 (1.06%) of 4908 patients treated with varenicline and in 27 (0.82%) of 3308 taking placebo. This difference was statistically significant.4

Until more data become available, the benefit of varenicline in helping patients stop smoking would appear to outweigh the risks of the drug.

1. Drugs for tobacco dependence. Treat Guidel Med Lett 2008; 6:61.

2. FDA Safety Communication: Chantix (varenicline) may increase the risk of certain cardiovascular adverse events in patients with cardiovascular disease. Available at www.fda.gov/Drugs/DrugSafety/ucm259161.htm. Accessed August 15, 2011.

3. NA Rigotti et al. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial. Circulation 2010; 121:221.

4. S Singh et al. Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ 2011 July 4 (epub).

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The goals of drug therapy for chronic obstructive pulmonary disease (COPD) are to reduce symptoms such as dyspnea, improve exercise tolerance and quality of life, and decrease complications of the disease such as acute exacerbations. Other guidelines for treatment of this condition have been published or updated in recent years.

The most effective drugs available for treatment of tobacco dependence are bupropion (Zyban, and others and varenicline (Chantix). The FDA recently ordered the manufacturers of both to add boxed warnings about the risk of psychiatric symptoms and suicide to their prescribing information (FDA Alert, 7/1/2009).

Peptic ulcers caused by treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) are mainly gastric ulcers. The greater the number of office visits and the longer the counseling time, the higher the smoking cessation rates have been.

When the nicotine receptor partial agonist varenicline (Chantix – Pfizer) was first marketed, The Medical Letter concluded that it was moderately effective in increasing smoking cessation rates.1 More recent publications and the clinical experience of Medical Letter consultants now suggest that varenicline is the most effective drug available for this indication, more effective than nicotine replacement therapy or bupropion SR (Zyban).2,3 A word of caution: exacerbations of psychiatric illness have been reported in patients who took higher-than-recommended starting doses of varenicline.4,5

1. Varenicline (Chantix) for tobacco dependence. Med Lett Drugs Ther 2006; 48:66.
2. P Wu et al. Effectiveness of smoking cessation therapies: a systemic review and meta-analysis. BMC Public Health 2006; 6:300.
3. K Cahill et al. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2007; (1):CD006103.
4. R Freedman. Exacerbation of schizophrenia by varenicline. Am J Psychiatry 2007; 164:1269.
5. I Kohen and N Kremen. Varenicline-induced manic episode in a patient with bipolar disorder. Am J Psychiatry 2007; 164:1269.

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The goals of drug therapy for chronic obstructive pulmonary disease (COPD) are to reduce symptoms such as dyspnea, improve exercise tolerance and quality of life, and minimize complications of the disease such as acute exacerbations and cor pulmonale. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines developed by the World Health Organization and the National Heart, Lung and Blood Institute were updated in 2006. The American Thoracic Society and the European Respiratory Society jointly developed guidelines for COPD in 2004.

Varenicline tartrate (Chantix - Pfizer) is now available for oral treatment of tobacco dependence. Some other drugs for this indication are listed in this article.

Management of intermittent claudication, the most common symptom of peripheral arterial disease (PAD), involves both risk factor modification and symptomatic treatment (WR Hiatt, N Engl J Med 2001; 344:1608; RM Schainfeld, J Am Board Fam Pract 2001; 14:443).

Tobacco dependence is a chronic illness that may require pharmacological treatment (MC Fiore et al, JAMA 2000; 283:3244; DPL Sachs in JE Hodgkin et al, eds, Pulmonary Rehabilitation: Guidelines to Success, 3rd ed, Philadelphia; Lippincott Williams & Wilkins, 2000, page 261).