Abstract: 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.  One trial of taranabant was not included in our meta-analyses, as it followed participants only until end of treatment; at eight weeks it found no benefit for treatment over placebo, with an OR of 1.2 (90% CI 0.6 to 2.5).  For rimonabant, 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. For taranabant, weight gain was significantly lower for 2-8 mg versus placebo at the end of eight weeks of treatment.  In 2008, post-marketing surveillance led the European Medicines Agency (EMEA) to require Sanofi Aventis to withdraw rimonabant, because of links to mental disorders. The development of taranabant was also suspended by Merck & Co because of unacceptable adverse events. From the trial reports available, rimonabant 20 mg may increase the chances of quitting approximately 1½-fold. The evidence for rimonabant in maintaining abstinence is inconclusive.  Rimonabant 20 mg may moderate weight gain in the long term. Taranabant 2-8 mg may moderate weight gain, at least in the short term.  In 2008, development of both rimonabant and taranabant was discontinued by the manufacturers.

Plain-language summary: 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. The available information shows 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 with rimonabant 20 mg were 1½ times more likely to remain abstinent on active treatment (5 mg or 20 mg for 42 weeks) 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. One trial of taranabant (317 smokers) did not find a benefit for treatment over placebo, and the taranabant group suffered more side effects than the placebo group. Main side effects for rimonabant included nausea and upper respiratory tract infections, and serious harms were reported to be low. For taranabant, the main side effects included problems with digestive, nervous, psychiatric, skin and blood vessel organ systems. For both drugs, the number and severity of the side effects increased in those taking higher doses. Although the evidence on weight change is sparse in these trials, weight gain was reported to be significantly lower among the rimonabant 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. Taranabant also limited weight gain during cessation attempts. In 2008 both rimonabant and taranabant were withdrawn by the manufacturers, because of links to mental disorders and unacceptable side effects.