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Q/ Which smoking cessation interventions work best?


A/ NICOTINE REPLACEMENT THERAPY (NRT), bupropion, nortriptyline, clonidine, and varenicline are all effective, although insufficient evidence exists to recommend one intervention over another (SOR: A, systematic reviews).

Effective nonpharmacologic interventions include brief physician advice and more intensive counseling, such as proactive telephone counseling, group and individual counseling, and use of quit lines (SOR: A, systematic reviews).

Evidence summary

NRT. A Cochrane review of 111 randomized controlled trials (RCTs) with a total of >40,000 subjects evaluated abstinence rates after 6 months of NRT and placebo or no treatment. (1) All forms of NRT increased abstinence vs placebo or no treatment, independent of setting, duration of treatment, and intensity of non-pharmacologic therapies. Overlapping confidence intervals suggested that no one form of NRT was superior. (The TABLE summarizes all the studies discussed here.)

* Bupropion. A Cochrane review of 36 RCTs (N=11,140) showed higher abstinence rates with bupropion than placebo after [greater than or equal to] 6 months of follow-up (average quit rate 17% vs 9%). Duration (6 vs 12 months) and intensity (150 vs 300 mg) of therapy didn't influence the results. (2) Six separate RCTs comparing bupropion plus NRT with NRT alone showed significant heterogeneity, but found no significant differences using a mixed-effects model. (2)

* Nortriptyline. A Cochrane review that pooled results from 6 RCTs (N=975) showed superior 6-month abstinence rates for nortriptyline compared with placebo. (2) Adding nicotine patches in other RCTs (N=1219) didn't change abstinence rates. (2) No long-term studies have examined other tricyclic antidepressants.

* Clonidine. A pooled analysis of 6 RCTs found clonidine superior to placebo after [greater than or equal to] 12 weeks of follow-up. (3) Results were heavily influenced by one trial limited to heavy smokers and poor tolerability due to adverse effects of therapy, especially sedation and dry mouth.

* Nicotine receptor partial agonists and antagonists. Standard dose varenicline was more than twice as likely as placebo to produce abstinence at 6 months in a Cochrane review of 10 RCTs. (4) Lower doses were slightly less effective, but had fewer side effects. Adverse effects included mild to moderate nausea and sleep disorders; causation has not been established between varenicline and rare postmarketing reports of severe psychiatric disturbances. (4,5)

The pooled results of 3 RCTs suggested that varenicline was superior to bupropion, but different abstinence rates for bupropion users in other placebo-controlled trials necessitate caution in interpreting these results. (4) Varenicline was not superior to NRT. (4)

One RCT (N=48) comparing nicotine patches plus the nicotine antagonist mecamylamine with patches plus placebo found improved abstinence rates at 6 and 12 months; a larger RCT didn't support these findings. (6)

These interventions are not supported

A review of placebo-controlled RCTs found no evidence of improved abstinence at 6 to 12 months with fluoxetine, paroxetine, sertraline, venlafaxine, citalopram, or monoamine oxidase inhibitors, alone or as adjuncts to NRT. (2)

No good evidence supports using anxiolyrics, silver acetate, Nicobrevin (a nicotinefree smoking cessation aid), lobeline, or naltrexone for smoking cessation. (7-9)

Simple advice and quit lines help

A Cochrane review of 17 RCTs found that simple advice improved quit rates and maintenance of abstinence at 12 months. (10-13)

A review of 9 RCTs (N>24,000) found that telephone quit lines increased abstinence, particularly after more than 2 sessions. (14)

No high-quality studies demonstrate the effectiveness of acupuncture, hypnotherapy, or acupressure for smoking cessation. (15,16)


The Agency for Health Care Research and Quality recommends counseling (including individual, group, and telephone sessions and brief physician advice) in addition to sustained-release bupropion, NRT, and varenicline as first-line agents. It considers clonidine and nortriptyline second-line therapies. (17)

Smoking cessation: Help patients stop (and get paid for it)

Elliot Wineburg, MD, Director, Stop Smoking Medical Center, New York, NY


(1.) Silagy C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2008;(3):CD000146.

(2.) Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2010;(4):CD000031.

(3.) Gourlay SG, Stead LF, Benowitz NL. Clonidine for smoking cessation. Cochrane Database Syst Rev. 2008;(3):CD000058.

(4.) Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2011;(2):CD006103.

(5.) Product Information for Chantix. New York, NY: Pfizer; 2006.

(6.) Lancaster T, Stead LF, Mecamylamine for smoking cessation. Cochrane Database Syst Rev. 2009;(1):CD001009.

(7.) Hughes JR, Stead LF, Lancaster T. Anxiolytics for smoking cessation. Cochrane Database Syst Rev. 2010;(1):CD002849.

(8.) Lancaster T, Stead LF. Silver acetate for smoking cessation. Cochrane Database Syst Reu 2009;(2):CD000191.

(9.) David S, Lancaster T, Stead LF, et al. Opioid antagonists for smoking cessation. Cochrane Database Syst Rev. 2009;(4):CD003086.

(10.) Lancaster T, Stead LF. Self-help interventions for smoking cessation. Cochrane Database Syst Rev. 2009;(2):CD001118.

(11.) Lancaster T, Stead LF. Physician advice for smoking cessation. Cochrane Database Syst Rev 2008;(2):CD000165.

(12.) Lancaster T, Stead LF. Individual behavioral counseling for smoking cessation. Cochrane Database Syst Rev. 2008;(4):CD001292.

(13.) Stead LF, Lancaster T. Group behavior therapy programs for smoking cessation. Cochrane Database Syst Rev. 2009;(2):CD001007.

(14.) Stead LF, Perera R, Lancaster T. Telephone counseling for smoking cessation. Cochrane Database Syst Rev. 2009;(3):CD002850.

(15.) White AR, Rampes H, Campbell JL. Acupuncture and related interventions for smoking cessation. Cochrane Database Syst Rev. 2008;(4):CD000009.

(16.) Abbot NC, Stead LF, White AR, et al. Hypnotherapy for smoking cessation. Cochrane Database Syst Rev. 2010;(10):CD001008.

(17.) Fiore MC, Jaen CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 Update. Rockville, MD: US Department of Health and Human Services, Public Health Service; May 2008.

Tracy Mahvan, PharmD; Rocsanna Namdar, PharmD; Kenton Voorhees, MD; Peter C. Smith, MD

University of Wyoming School of Pharmacy, Laramie (Dr. Mahvan); University of Colorado School of Pharmacy, Aurora (Dr. Namdar); University of Colorado School of Medicine, Denver (Dr. Voorhees); Rose Family Medicine Residency, Denver (Dr. Smith)

Donna Flake, MSLS, MSAS

Health Sciences Library, Southeast Area Health Education Center, Wilmington, NC


Gary Kelsberg, MD

Valley Family Medicine Residency, Renton, Wash
How effective are smoking cessation interventions?

                                          Effect size *
                               No. of    (95% confidence
Intervention                   studies      interval)       Total N

NRT vs placebo or no             111     1.58 (1.50-1.66)   >40,000
  treatment (1)
Bupropion vs placebo (2)         36      1.69 (1.53-1.85)   11,140
Bupropion 300 mg/d vs             3      1.08 (0.93-1.26)    2042
  150 mg/d (2)
Bupropion + NRT vs NRT (2)        6      1.23 (0.67-2.26)    1106
Nortriptyline vs placebo (2)      6      2.03 (1.48-2.78)     975
Nortriptyline + NRT vs            4      1.29 (0.97-1.72)    1219
  NRT (2)
Clonidine vs placebo (3)          6      1.63 (1.22-2.18)     776
Varenicline vs placebo,          10      2.31 (2.01-2.66)    4443
  standard dose (4)
Varenicline vs placebo,           4      2.09 (1.56-2.78)    1272
  low dose (4)
Varenicline vs bupropion (4)      3      1.52 (1.22-1.88)    1622
Varenicline vs NRT (4)            2      1.13 (0.94-1.35)     778
Mecamylamine + NRT vs NRT+        1       37.5% vs 12.5%      48
  placebo (6)
Simple advice vs usual           17      1.66 (1.42-1.94)   15,930
  care (10-13)
Patient-initiated telephone       9      1.37 (1.26-1.50)   24,000
  quit line vs usual
  care (14)

NRT nicotine replacement therapy.

* An effect size >1.0 means that patients using this intervention
are more likely not to smoke at 6 to 12 months; larger
numbers correlate with greater effectiveness.
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Title Annotation:CLINICAL INQUIRIES: Evidence-based answers from the Family Physicians Inquiries Network
Author:Mahvan, Tracy; Namdar, Rocsanna; Voorhees, Kenton; Smith, Peter C.; Flake, Donna
Publication:Journal of Family Practice
Geographic Code:1USA
Date:Jul 1, 2011
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