Stapleton JA, et al. Varenicline in the routine treatment of tobacco dependence: a pre-post comparison with nicotine replacement therapy and an evaluation in those with mental illness. Addiction 2008;103:146-54. doi:10.1111/j.1360-0443.2007.02083.x
What is the background to this?
Varenicline (Champix▼) is a non-nicotine aid to smoking cessation that was first marketed in the UK in December 2006. Published data comparing the effectiveness of varenicline with nicotine replacement therapy (NRT) are limited. In this evaluation from an NHS tobacco dependence clinic in London, short-term cessation rates were compared using consecutive routine cases before and after the introduction of varenicline – so this was not a randomised controlled trial (RCT) and there is no indication that allocation was concealed.
What does this study claim?
In this setting and with group support, varenicline appeared to improve success rates over those achieved with NRT. However, significantly more patients taking varenicline than NRT experienced adverse drug reactions. Carbon monoxide (CO)-verified abstinence four weeks after ‘quit day’ was 72.1% (150/208 patients) with varenicline and 61% (125/204 patients) with NRT, a difference of 10.8% (95% CI 1.8% to 19.9%); odds ratio 1.63 (95% CI 1.08 to 2.47). When combination and single-product NRT was analysed separately, varenicline was significantly more effective than single-product NRT but not combination.
The authors claim that varenicline is equally effective and safe in those with and without mental illness, but this is based on a very small cohort of just 111 smokers, and varenicline has recently been the subject of a safety review in this area – see below.
How does this relate to other studies?
In July 2007, NICE recommended varenicline as an option for smoking cessation, normally as part of a programme of behavioural support. Based mainly on indirect comparisons and a confidential open-label trial (n=957) comparing varenicline with NRT, NICE concluded that varenicline was superior to NRT in achieving continuous abstinence.
In December 2007, the Medicines and Healthcare products Regulatory Agency announced an update to the product information for varenicline (Champix® ▼) highlighting concerns over suicidal thoughts and behaviour. Following a European review in conjunction with the European Medicines Agency (EMEA) it was recommended that:
Clinicians should already be aware of the risk of using varenicline in patients who have an underlying mental illness. The SPC currently reads, “Smoking cessation, with or without pharmacotherapy, has been associated with the exacerbation of underlying psychiatric illness (e.g. depression). Care should be taken with patients with a history of psychiatric illness and patients should be advised accordingly.”
Clinicians should advise patients who are trying to stop smoking that they can develop symptoms of depression.
Patients who develop suicidal thoughts while taking varenicline should stop their treatment and contact their doctor immediately.
The effectiveness data from the current study concurs with NICE guidance, adding to the limited published information comparing varenicline with NRT in smoking cessation. Ideally, evidence from a high quality prospective RCT with allocation concealment is required to fully judge the place in therapy of varenicline. In addition, recent guidance from the MHRA would dispute the safety data they present for the use of varenicline in patients with mental illness.
A section devoted to smoking cessation is available on NPC
Healthcare professionals should follow current NICE and MHRA guidance. Varenicline is an option in smoking cessation, but its use should be avoided in patients with underlying mental illness.
Design: Evaluation of consecutive routine cases before and after the introduction of varenicline. This was not a randomised controlled trial and no indication is given that allocation was concealed
Patients: 412 cases receiving routine care in an NHS tobacco dependence clinic in London.
Intervention and Comparison: Seven group support sessions over six weeks with either NRT (n = 204) or varenicline (n = 208).
Outcomes and Results: CO-verified abstinence four weeks after ‘quit day’ was 72.1% (150/208 patients) with varenicline and 61% (125/204 patients) with NRT, a difference of 10.8% (95% CI 1.8% to 19.9%); odds ratio 1.63 (95% CI 1.08 to 2.47). When combination and single-product NRT was analysed separately, varenicline was significantly more effective than single-product NRT but not combination (cessation rates of 72.1%, 57.9% and 66.3%, respectively; odds ratio 1.88 [95% CI 1.18 to 3.02] for varenicline vs. single-product NRT). Significantly more patients taking varenicline than NRT experienced adverse drug reactions, including nausea, disturbed sleep, vivid dreams, drowsiness, constipation, headache, dyspepsia, dry mouth, bad taste, low mood/depression, diarrhoea and disorientation/confusion. Nausea occurred in 38% of the varenicline group and disturbed sleep in 30%, compared with 1% and 6%, respectively, in the placebo group. The authors claim that varenicline is equally effective and safe in those with and without mental illness, but this is based on a very small cohort of just 111 smokers (NRT, n = 58, varenicline, n = 53).
Sponsorship: This study was conducted without the involvement of any commercial organisation.