Medications / Pharmacotherapy

Clinicians should encourage all patients attempting to quite to use effective medications for tobacco dependence treatment except where contraindicated or for special populations for which there is insufficient evidence of effectiveness.

Overview of Medications

· Non-nicotine medications for smoking cessation work through varying biological mechanisms to increase the likelihood of achieving a successful smoking cessation attempt.  Some work as agonists which tie to a receptor site in the brain causing an increase in reaction and others work as antagonists which tie to a receptor site and work against a substance by blocking the response.  

· Non-nicotine medications work to decrease cravings or decrease the feeling effect of the nicotine.  Similar to NRT, non-nicotine medications have been found to be efficacious when combined with counseling and is recommended that when possible, clinicians should provide multiple counseling sessions, in addition to medications, to their patients who are trying to quit smoking.

· In a large, multinational clinical trial, including people with and without psychiatric disorders, Anthenelli et al. (2016) found that Varenicline was more effective than placebo, nicotine patch, and Buproprion in helping smokers achieve abstinence.  Buproprion and the nicotine patch were more effective than placebo.  Despite past concerns, neuropsychiatric adverse events (e.g. suicidality risk and aggression) were not significantly higher with either Varenicline or Bupropion treatment relative to nicotine patch or placebo.  This finding was true for those with and without psychiatric disorders.4  

Forms of Medications

Medications Strength of Evidencea Availability
1st Lineb    
Bupropion SR (Sustained Release) A Rx
Varenicline A Rx
2nd Linec    
Clonidine (oral and transdermal) A Rx
Nortriptyline A Rx

1st lineb: First-line medications are those that have been found to be safe and effective for tobacco treatment and that have been approved by the FDA for this use, except in the presence of contraindications or with special populations for which there is insufficient evidence of effectiveness.

2nd linec: Second-line medications are medications for which there is evidence of effectiveness for treating tobacco dependence, but they have a more limited role than first-line medications because: 1) the FDA has not approved them for a tobacco dependence treatment indication; and 2) there are more concerns about potential side effects than exist with the first-line medications.

Rx = prescription only

Adapted from TTUD


Strength of Evidencea:  The Department of Health and Human Services’ Treating Tobacco Use and Dependence (TTUD) Clinical Practice Guidelines 2008 Update includes a comprehensive review of cessation effectiveness research based on the following guidelines.

Strength of Evidence A = Multiple well-designed randomized clinical trials, directly relevant to the recommendation, yielded a consistent pattern of findings.

Strength of Evidence B = Some evidence from randomized clinical trials supported the recommendation, but the scientific support was not optimal.

Strength of Evidence C = Reserved from important clinical situations in which the Panel achieved consensus on the recommendation in the absence of relevant randomized controlled trials.

Review Studies on Non-nicotine Medications

Studies have been fairly consistent in showing the efficacy of using non-nicotine pharmacotherapy to assist in abstaining from tobacco use.  In a meta-analysis on the randomized controlled trials for both nicotine replacement therapy and non-nicotine pharmacotherapy, results indicated that the non-nicotine pharmacotherapy lead to two times greater abstinence when compared to placebo.2  Reviews of the literature support the use of non-nicotine pharmacotherapy as a first line treatment for tobacco dependence in combination with NRT and psychosocial treatments when possible and if recommended considering the population.1,3

  1. Fiore, M. C., Jaen, C. R., Baker, T. B., & al., e. (2008). Treating Tobacco Use and Dependence 2008 Update.  Clinical Practice Guideline. In U.S. Department of Health and Human Services (Ed.). Rockville, MD: U.S. Department of Health and Human Services.
  2. Eisenberg, M. (2008). Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials. CMAJ: Canadian Medical Association Journal, 179(2), 135-144.
  3. Aubin, H., Karila, L., & Reynaud, M. (2011). Pharmacotherapy for smoking cessation: present and future. Current Pharmaceutical Design, 17(14), 1343-1350.
  4. Anthenelli, R. M., Benowitz, N. L., West, R., St Aubin, L., McRae, T., Lawrence, D., ... & Evins, A. E. (2016). Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. The Lancet.