Overview of Reviews

You have free access to this content

Pharmacological interventions for smoking cessation: an overview and network meta-analysis

  1. Kate Cahill*,
  2. Sarah Stevens,
  3. Rafael Perera,
  4. Tim Lancaster

Editorial Group: Cochrane Tobacco Addiction Group

Published Online: 31 MAY 2013

Assessed as up-to-date: 16 NOV 2012

DOI: 10.1002/14651858.CD009329.pub2

How to Cite

Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD009329. DOI: 10.1002/14651858.CD009329.pub2.

Author Information

  1. University of Oxford, Department of Primary Care Health Sciences, Oxford, UK

*Kate Cahill, Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK. kate.cahill@phc.ox.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 31 MAY 2013

SEARCH

 
Table 1. Characteristics of included reviews

Review IDAssessed as up-to-dateParticipants 

Interventions
 

Comparisons
 

Outcomes
 

N Pts/trials
Review limitations

Antidepressants

Hughes 2007
June 2009Current smokers, mostly adult but two studies of adolescents

 
Bupropion1.  vs placebo
2.  + NRT vs NRT alone
3.  vs patch
4.  vs varenicline
6m+ abstinence:
- all;
- by setting;
- by level of behavioural support;
- by dosage.
1.11440/36
2. 1106/6
3. 657/3
4. 1622/3
Biochemical validation was reported in all B trials except Swan 2003, and in all N trials except Da Costa 2002.
Four B trials included based on abstracts only.
Sensitivity analyses of each limitation made no difference to findings.

 

Nortriptyline1.  vs placebo
2.  +NRT vs NRT alone
3.  vs NRT
6-12m1. 975/6
2. 1219/4
3. 417/3

Fluoxetine1.  vs placebo
2. +NRT vs placebo+NRT
6 or 12m1. 1236/2
2. 250/2

Paroxetine vs placebo6m224/1

Sertraline vs placebo6m134/1

MAOIs:
Moclobemide
Selegiline
1.  vs placebo
2.  vs placebo
12m, 6m1. 88/1
2. 250/3

Venlafaxine +NRT vs placebo+NRT12m147/1

Anxiolytics

Hughes 2011
October 2009Any smokersBuspirone1.  vs placebo
2.  vs NRT
1. 12m
2. 6m
409/4Most trials did not report methods in enough detail to assess quality of randomisation.
Abstinence often not clearly defined or bio-validated.
Meprobamate outcome was reduction, not abstinence.

Diazepam vs placebo6m76/1

Meprobamate1.  vs placebo
2.  +individual counselling vs placebo
3.  +group counselling vs placebo
reduction >85% at12m216/1

Oxprenololvs placebo12m130/1

Metoprolol

CB1 receptor antagonists (rimonabant)

Cahill 2011
January 2011Adult smokersRimonabant1.  20mg vs placebo
2.  5mg vs placebo
3. 20mg vs 5mg
50 weeks1049/2Study reports unpublished, not peer-reviewed

Taranabant1.  vs placebo8 wksN/AN/A

Clonidine
Gourlay 2008
June 2008Adult smokers (4/6 trials specified heavy smokers)Clonidine1. C vs placebo6m or 12m776/6No details of randomisation or blinding; Abstinence not clearly defined

Lobeline
Stead 2009
January 2009Any smokersLobeline1. vs placebo
2. vs any treatment
6m+0/0N/A

Mecamylamine
Lancaster 2011
December 2010Healthy volunteer smokersMecamylamine1. +NRT vs placebo+NRT
2. +NRT vs M vs NRT vs placebo
6m or 12m128/2
(no MA)
Studies too small to be conclusive

Nicobrevin
Stead 2009
January 2009Adult smokersNicobrevin1. vs placebo6m0/0N/A

Nicotine vaccines
Hartmann-Boyce 2012
2012 Adult smokers 

NicVAX
1. vs placebo

2. High Ab vs placebo

3. 400 vs 200

- 4 shots

- 5 shots

4. 5 vs 4 shots

- 200ug

- 400ug
 

 

12m, 6m
 

 

201/1
Hatsukami 2011 stratified active group to give the highest level of statistical significance. Nabi trials gave insufficient info to assess.

NIC002 

1. vs placebo

2. High Ab vs placebo
12m, 6m341/1 Possibly post-hoc stratification to give significant results.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

NRT

Stead 2013
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

October 2012
 

 

 

 

 

 

 

 

 

Adult smokers (not trials that randomised therapists)

 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Nicotine Replacement Therapy
1. Any NRT vs placebo
1. Gum
2. Patch
3. Inhaler

4. Nasal spray
5. Tabs/lozenge
6. Oral spray
7. Choice of NRT

8. Patch + Inhaler

9. Patch + lozenge
6m+51265/119
22581/56
19586/43
976/4

887/4
3405/7
479/1
2798/5

245/1

308/1
In 1.1, 2 trials (Shiffman 2002, Shiffman 2009) split into separate dosage comparisons 

 

 

 

 

 

 

 

 

26% of studies rated as at low risk of bias for randomisation, and 5% at high risk. Excluding all but low risk made little difference.

Variable definitions of abstinence, including 4 trials allowing up to 4 cpd; excluding these made no difference.

65% reported sustained abstinence, and 80% measured to 12m or more.

89% used some form of validation.

One third reported some type of blinding.

2. Abstinence definition:
1 Gum
2 Patch
-Sus 12m
-Sus 6m
-PP/ns 12m
-PP/ns 6m
22581/56
13737/32

4187/8

2501/8
2156/8

19586/43

10928/21
4640/9
2582/6
1436/7

3. Level of support:
1. Gum
2. Patch
3. Long vs short:
-Gum
-Patch
Gum or patch:
- Low
-High individual
-High group
Long vs Short:
-Gum
-Patch
21759/55
-11257/17
-6891/18
-3611/20

19585/43
-4388/12
-11559/22
-3638/10

800/3
-296/2
-504/1

4. Setting for Recruitment/Treatment:

1. Community
1. Gum

2. Patch

3. Inhaler

4. Tab/lozenge

5. Nasal spray

6. Combo

7. Oral spray
2. SC Clinic

1. Gum

2. Inhaler

3. Nasal spray
3. Primary care

1. Gum

2. Patch

3. Choice
4. Hospitals

1. Gum

2. Patch

3. Combo

4. Choice
5. Antenatal clinic

1. Gum

2. Patch

3. Choice

6. OTC volunteers

1. Gum

2. Patch
6m+24199/66
8336/28
10816/28
443/2
3405/7

412/2

308/1

479/1

2291/10

1283/6

533/2

475/2

11705/23

7277/16

4150/6

278/1

5506/10

2194/3

1042/4

245/1

2025/2

1675/4

194/1

1300/2

181/1

5575/5

3297/2

2278/3

5. Dosage of gum
1. 4mg vs 2mg
-High dependence
-Low dependence
6m+856/5
618/4
238/3

6. Gum: Fixed vs ad-lib

gum
6m+689/2

7. 1. Patch: High vs standard dosage
1. 44mg vs 22mg

2. 42mg vs 21mg
2. 25mg vs 15mg
6m+5101/8
1188/4

467/1
3446/3

8. 1. Patch: duration
1. 16hr vs placebo
2. 24hr vs placebo
3. 24hr vs 16hr
6m+/42
7618/11
10820/32
106/1

9. 1. Patch: Course of treatment:
1. ≤8 wks
2. >8 wks

2. Direct comparison
1. 28 wks vs 12 wks

2. 24 wks vs 8 wks
3. 12 wks vs 3 wks
4. 12 wks vs 6 wks
5. 6 wks vs 3 wks
6m+/42
6191/17
9906/26

/5
2861/1

568/1
98/1
140/1
80/1

10. 1. Indirect comparison
1. patch vs placebo; no weaning
2. patch vs placebo; with weaning

2. Direct comparison
1. patch; abrupt withdrawal vs weaning
6m+17427/41
2807/9

14620/32

264/2

11. Combinations:

1. Long-term Smoking cessation
1. patch+gum vs patch alone
2. patch+gum vs gum alone
3. spray+patch vs patch alone
4. spray+patch vs spray or patch
5. patch+inhaler vs inhaler alone
6. patch+inhaler vs patch or inhaler
7. patch+lozenge vs patch or lozenge
6m+4664/9
395/2

300/1
237/1
1384/1
400/1
337/1
1611/2

12. Direct comparisons between NRTs

1. Smoking cessation
1. inhaler vs patch
2. spray vs patch

3. Lozenge vs patch
6m+.3201/6
222/1
1272/2

1707/3

13. Prescribed NRT with physician support vs OTC NRT without support

1.1 patch

1.2 inhaler
6m+820/2

300/1

520/1

14. 1. Precessation NRT

1. Patch

2. Gum

3. Lozenge
6m+2774/8

1772/6

406/2

596/1

15.1 NRT in pregnancy

1. At end of pregnancy

2. At longest post-partum follow-up.
1675/4

625/3

16. 1. NRT v bupropion
1. patch vs bup
2. Lozenge vs bup

3. Choice vs bup
2. Combination vs bupropion alone

1. Patch + bup vs bup alone

2. Gum + bup vs bup alone

3. Lozenge + bup vs bup alone

3. Combination vs placebo

1. Patch + bup vs placebo

2. Lozenge+bup vs placebo
6m+2544/5

1552/4
781/2

211/1

1991/3

489/1

452/1

526/1

1991/4

405/1

299/1

17. Palpitations with NRT vs placebo

1. Palpitations/chest pains

Nicotine receptor partial agonists

Cahill 2012
April 2012Any adult smokersCytisine1. Cytisine (Tabex)
1. vs placebo
6m or 12m937/2Well-conducted trials

Dianicline2. Dianicline
1. vs placebo
6m602/1Well-conducted trial

Varenicline3. Varenicline 1mg bid
1. vs placebo
2. vs placebo
3. vs placebo in pts with schizophrenia
6m+
12+m
6m
6166/14
378/1
127/1
Trials were generally conducted to a high standard, with biochemically validated outcomes.

4. Low-dose varenicline
1. V vs placebo
2. Standard V vs low-dose V
12m1272/4
1083/3

5. Varenicline
1. vs bupropion
2. vs bupropion
3. vs bupropion
12m
3m
6m
1622/3
1367/2
1367/2

6. Varenicline
1. vs NRT (open label)
6m778/2

7. Varenicline as maintenance therapy
1. vs placebo
2. vs placebo at end of double-blind phase
12m
6m
1208/1
1210/1

8. Commonest AEs
1. Nausea
2. Insomnia
3. Abnormal dreams
4. Headache
During 3m treatment6619/16
6309/15
5585/12
5913/13

10. SAEs
1. vs placebo
During and after treatment8175/17

Opioid antagonists
David 2009
June 2009Adult smokersNaltrexone1. vs placebo
2. +NRT vs placebo+NRT
6m or 12m582/4Wong reported data from only 1 of 4 centres

Silver acetate
Lancaster 2009
January 2009Adult smokersSilver acetate1. vs placebo
2. vs nicotine gum
12m785/2
414/1
randomisation not described. One trial was open-label.

 
Table 2. AMSTAR scores: NRT, antidepressants and nicotine receptor partial agonists

QuestionNicotine
Replacement
Therapy
BupropionNicotine
receptor partial agonists

1.A priori design provided?CAN'T ANSWERCAN'T ANSWERYES

2. Duplicate study selection and data extraction?YESYESYES

3. Comprehensive literature search performed?YESYESYES

4. Published and unpublished studies included?YESYESYES

5. List of included and excluded studies?YESYESYES

6. Characteristics of included studies provided?YESYESYES

7. Scientific quality of included studies assessed?YESYESYES

8. Scientific quality of included studies applied to conclusions?YESYESYES

9. Appropriate methods for combining studies?YESYESYES

10. Likelihood of publication bias?YESNONO

11. Conflict of interest stated?YESYESYES

SCORE10/119/1110/11

 
Table 3. AMSTAR scores: other pharmacotherapies

QuestionAnxiolyticsCB1 receptor antagonistsClonidineLobelineMecamylamineNicobrevinVaccinesOpioid antagonistsSilver acetate

1.A priori design provided?CAN'T ANSWERYESCANT ANSWERCAN'T ANSWERCAN'T ANSWERCAN'T ANSWERYESYESCAN'T ANSWER

2. Duplicate study selection and data extraction?YESYESYESYESYESYESYESYESYES

3. Comprehensive literature search performed?YESYESYESYESYESYESYESYESYES

4. Published and unpublished studies included?YESYESYESYESYESYESYESYESYES

5. List of included and excluded studies?YESYESYESYESYESYESYESYESYES

6. Characteristics of included studies provided?YESYESYESN/AYESN/AYESYESYES

7. Scientific quality of included studies assessed?YESYESYESN/AYESN/AYESYESYES

8. Scientific quality of included studies applied to conclusions?YESYESN/AYESN/AYESYESYES

9. Appropriate methods for combining studies?YESYESYESN/AN/AN/AYESYESYES

10. Likelihood of publication bias?NON/ANON/AYESN/AYESNON/A

11. Conflict of interest stated?YESYESYESYESYESYESYESYESYES

SCORE9/1110/109/115/69/105/611/1110/119/10

 
Table 4. Risk of bias summary for trials in the included reviews

ReviewN trialsrandomisation %Sustained
abstinence %
Biochemical
validation %
Blinding %

  






  Low
risk
Unclear
risk
High

risk
  Low risk

NRT14725723708633

Antidepressants6048502858550

Nic recep partial ags246633-758458

Anxiolytics7-100-29290

Clonidine6-100-0670

Lobeline0No included studies



Mecamylamine2100--100100100

Nicobrevin0No included studies



Nicotine vaccines42575-505050

Opioid antagonists45050-50100100

Rimonabant3-100-1001000

Silver acetate2-100-10010050

 Numbers from columns 3 to 8 are percentages of the total number of trials for each review.