Cytisine for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation

Piotr Tutka; Denis Vinnikov; Ryan J Courtney; Neal L Benowitz

doi:10.1111/add.14721

Cytisine for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation

Addiction. 2019 Nov;114(11):1951-1969. doi: 10.1111/add.14721. Epub 2019 Jul 19.

Authors

Piotr Tutka^{1

2

3}, Denis Vinnikov^{4

5}, Ryan J Courtney³, Neal L Benowitz^{6

7}

Affiliations

¹ Department of Experimental and Clinical Pharmacology, University of Rzeszów, Rzeszów, Poland.
² Laboratory for Innovative Research in Pharmacology, University of Rzeszów, Rzeszów, Poland.
³ National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia.
⁴ School of Public Health, Al-Farabi Kazakh National University, Almaty, Kazakhstan.
⁵ Biological Institute, National Research Tomsk State University, Tomsk, Russia.
⁶ Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
⁷ Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.

PMID: 31240783
DOI: 10.1111/add.14721

Abstract

Aims: To review cytisine's history of use, pre-clinical evidence, clinical pharmacokinetics, efficacy, adverse reactions (ARs) and safety for smoking cessation.

Methods: A synoptic review of the use of cytisine as a smoking cessation medication, mechanism of action, pharmacokinetics and safety. Relevant literature on data included in these sections were identified through a search of 11 databases with additional literature obtained from reports and monographs. Three databases (PubMed, EMBASE and www.elibrary.ru) were systematically searched for studies published from 2012 to August 2018 in any language to provide an updated meta-analysis of cytisine's efficacy and ARs for smoking cessation compared with placebo. We pooled the relative risks (RR) of abstinence in the efficacy analysis and RR of ARs, either reported by the authors or calculated from the reports.

Results: Cytisine has been in use since 1964 and is currently marketed in 18 countries. Systemic bioavailability from oral ingestion is high and clearance is primarily renal, with minimal or no metabolism. Brain uptake in animal models is moderate. The plasma half-life averages 4.8 hours. Eight studies were included for meta-analysis of efficacy. With heterogeneous results, the overall RR versus placebo of successful continuous abstinence at the longest follow-up was 1.74 [95% confidence interval (CI) = 1.38-2.19]. Nausea, vomiting, dyspepsia, upper abdominal pain and dry mouth that were mild or moderate were the most common ARs, with RR versus placebo 1.10 (95% CI = 0.95-1.28). The cost of cytisine in eastern and central Europe is several-fold less than that of other smoking cessation medications.

Conclusions: Cytisine is a low-cost medication found to increase the likelihood of smoking cessation. The most frequently reported ARs of cytisine involve gastrointestinal symptoms that are mostly reported as either mild or moderate in severity.

Keywords: Addiction; cessation; cytisine; low-/middle-income country; nicotine; nicotinic receptor partial agonist.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Alkaloids / pharmacology*
Alkaloids / therapeutic use*
Azocines / pharmacology
Azocines / therapeutic use
Clinical Trials as Topic
Humans
Quinolizines / pharmacology
Quinolizines / therapeutic use
Smoking Cessation / methods*
Tobacco Use Disorder / drug therapy*

Substances

Alkaloids
Azocines
Quinolizines
cytisine

Grants and funding

GNT148497/National Health and Medical Research Council Career Development Fellowship/International