Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation
Abstract
Background
Rimonabant is a selective type 1 cannabinoid (CB1) receptor antagonist. It may assist with smoking cessation by restoring the balance of the endocannabinoid system, which can be disrupted by prolonged use of nicotine. Rimonabant also seeks to address many smokers' reluctance to persist with a quit attempt because of concerns about weight gain.
Objectives
To determine whether selective CB1 receptor antagonists increase the numbers of people stopping smoking
To assess their effects on weight change in successful quitters and in those who try to quit but fail.
Search methods
We searched the Cochrane Tobacco Addiction Review Group specialized register for trials, using the terms 'rimonabant' and 'smoking' in the title or abstract, or as keywords. We also searched MEDLINE, EMBASE, CINAHL and PsycINFO, using major MESH terms. We acquired electronic or paper copies of posters of preliminary trial results presented at the American Thoracic Society Meeting in 2005, and at the Society for Research on Nicotine and Tobacco European Meeting 2006. We also attempted to contact the authors of ongoing studies of rimonabant, and Sanofi Aventis (manufacturers of rimonabant).
Selection criteria
Types of studies
Randomized controlled trials
Types of participants
Adult smokers
Types of interventions
Selective CB1 receptor antagonists, such as rimonabant.
Types of outcome measures
The primary outcome is smoking status at a minimum of six months after the start of treatment. We preferred sustained cessation rates to point prevalence, and biochemically verified cessation to self‐reported quitting. We regarded smokers who drop out or are lost to follow up as continuing smokers. We have noted any adverse effects of treatment.
A secondary outcome is weight change associated with the cessation attempt.
Data collection and analysis
Two authors checked the abstracts for relevance, and attempted to acquire full trial reports. One author extracted the data, and a second author checked them.
Main results
We found three trials which met our inclusion criteria, covering 1567 smokers (cessation: STRATUS‐EU and STRATUS‐US), and 1661 quitters (relapse prevention: STRATUS‐WW). At one year, the pooled risk ratio (RR) for quitting with rimonabant 20 mg was 1.50 (95% confidence interval (CI) 1.10 to 2.05). No significant benefit was demonstrated for rimonabant at 5 mg dosage. Adverse events included nausea and upper respiratory tract infections.
In the relapse prevention trial, smokers who had quit on the 20 mg regimen were more likely to remain abstinent on either active regimen than on placebo; the RR for the 20 mg maintenance group was 1.29 (95% CI 1.06 to 1.57), and for the 5 mg maintenance group 1.30 (95% CI 1.06 to 1.59). There appeared to be no significant benefit of maintenance treatment for the 5 mg quitters.
Weight gain was reported to be significantly lower among the 20 mg quitters than in the 5 mg or placebo quitters. During treatment, overweight or obese smokers tended to lose weight, while normal weight smokers did not.
Post‐marketing surveillance has led the European Medicines Agency (EMEA) to require themanufacturers to withdraw the drug, because of links to mental disorders.
Authors' conclusions
From the preliminary trial reports available, rimonabant 20 mg may increase the chances of quitting approximately 1½‐fold.
Adverse events include nausea and upper respiratory tract infections; the risk of serious adverse events is reported to be low. However, in October 2008 post‐marketing surveillance led to the withdrawal of rimonabant as a prescription drug in European countries, because of links to mental disorders.
The evidence for rimonabant in maintaining abstinence is inconclusive.
Rimonabant 20 mg may moderate weight gain in the long term.
PICOs
Plain language summary
Can rimonabant help smokers to quit, and could it also reduce the amount of weight gained during the quitting process
Long‐term use of nicotine can upset the endocannabinoid system in the brain, which controls food intake and energy balance. Rimonabant may help smokers to quit by rebalancing the system, which then reduces nicotine and food cravings. We searched our own specialised register of controlled trials. We also contacted Sanofi‐Aventis, the manufacturers of rimonabant, and researchers who presented early findings at conferences. We found two randomized controlled trials (RCTs) of rimonabant for smoking cessation, covering 1567 smokers, and one RCT of rimonabant for relapse prevention covering 1661 quitters. Although full trial reports are not yet published, our own analyses show that rimonabant at the 20 mg dose increased by 1½‐fold the chances of not smoking at one year, compared with placebo. Rimonabant 5 mg did no better than placebo at any time point. In the relapse prevention trial, smokers who quit successfully on rimonabant 20 mg were 1½ times more likely to remain abstinent on active treatment (5 mg or 20 mg) than on placebo. For those who quit successfully on 5 mg, neither active nor placebo treatment appeared to benefit them in avoiding relapse. This inconsistent picture makes it difficult to find a clear benefit for rimonabant in preventing relapse. Although the evidence on weight change is sparse in these trials, weight gain was reported to be significantly lower among the 20 mg quitters than in the 5 mg or placebo quitters. During treatment, overweight or obese smokers tended to lose weight on 20 mg, while normal weight smokers did not. Main side effects were nausea and upper respiratory tract infections, and serious harms were reported to be low. However, in October 2008 rimonabant was withdrawn as a prescription drug in European countries, because of links to mental disorders.
