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Nortriptyline plus nicotine replacement versus placebo plus nicotine replacement for smoking cessation: pragmatic randomised controlled trial

BMJ 2008; 336 doi: https://doi.org/10.1136/bmj.39545.852616.BE (Published 29 May 2008) Cite this as: BMJ 2008;336:1223

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  1. Paul Aveyard, National Institute for Health Research career scientist1,
  2. Carol Johnson, lecturer2,
  3. Sally Fillingham, research associate1,
  4. Amanda Parsons, research associate1,
  5. Mike Murphy, consultant epidemiologist3
  1. 1Division of Primary Care and Public Health, University of Birmingham, Birmingham B15 2TT
  2. 2School of Health Sciences, University of Birmingham
  3. 3Childhood Cancer Research Group, University of Oxford
  1. Correspondence to: P Aveyard p.n.aveyard{at}bham.ac.uk
  • Accepted 20 March 2008

Abstract

Objective To test the efficacy of nortriptyline plus nicotine replacement therapy compared with placebo plus nicotine replacement therapy for smoking cessation.

Design Pragmatic randomised controlled trial.

Setting National Health Service stop smoking service clinics.

Participants 901 people trying to stop smoking.

Interventions Participants chose their nicotine replacement product, including combinations of nicotine replacement therapy, and received behavioural support. Nortriptyline was started one to two weeks before quit day, with the dose increased from 25 mg to 75 mg daily for eight weeks and reduced if not tolerated.

Main outcome measures Primary outcome was prolonged confirmed abstinence at six months. Secondary outcomes were prolonged abstinence at 12 months, drug use, severity of side effects, nicotine withdrawal symptoms, and urges to smoke.

Results 72 of 445 (16%) people using nortriptyline and 55 of 456 (12%) using placebo achieved prolonged abstinence at six months (relative risk 1.34, 95% confidence interval 0.97 to 1.86). At 12 months the corresponding values were 49 (11%) for nortriptyline and 40 (9%) for placebo (1.26, 0.84 to 1.87). 337 (79%) people in the nortriptyline arm and 325 (75%) in the placebo arm were taking combination treatment on quit day, median 75 mg per day in both groups. More people in the nortriptyline arm than in the placebo arm took lower doses. The nortriptyline arm had noticeably higher severity ratings for dry mouth and constipation than the placebo arm, with slightly higher ratings for sweating and feeling shaky. Both groups had similar urges to smoke, but nortriptyline reduced depression and anxiety. Overall, withdrawal symptom scores did not differ.

Conclusions Nortriptyline and nicotine replacement therapy are both effective for smoking cessation but the effect of the combination is less than either alone and evidence is lacking that combination treatment is more effective than either alone.

Trial registration Current Controlled Trials ISRCTN57852484.

Footnotes

  • We thank the stop smoking services in South Birmingham, Warwickshire, Buckinghamshire, Gwent, Hertfordshire, Coventry, Sandwell, Walsall, Wolverhampton, and Black Water Valley and Hart.

  • Contributors: PA and MM wrote the protocol, with contributions from Robert Walton and Mark Drury. CJ, SF, AP, and PA ran the study. Mike Bradburn (statistician, Cancer Research UK Medical Statistics Unit) prepared the randomisation schedule. PA, AP, and CJ analysed the data with help from Michelle Qume. PA drafted the paper, with help from all authors. PA is the guarantor.

  • Funding: The trial was funded by Cancer Research UK and NHS Support for Science. These are the views of the authors and not necessarily the funders. PA is funded by the National Institute for Health Research. King Pharmaceuticals donated nortriptyline for the study.

  • Competing interests: PA has done consultancy work for the pharmaceutical and biotechnology industry that has led to payments to him and his institution. This includes work for companies providing smoking cessation treatment, including nicotine replacement therapy. MM has received consultancy income from the European Network for Smoking Prevention and has provided scientific consultancy services through the University of Oxford ISIS Innovation to the National Audit Office and G-Nostics.

  • Ethical approval: We obtained approval from the multicentre research ethics committee and all local research ethics committees for the areas in which our trial took place. We obtained a clinical trials authorisation from the Medicines and Healthcare products Regulatory Agency. We obtained approval from all NHS research and development offices of the primary care organisations for the areas in which our trial took place.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Accepted 20 March 2008
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