Acomplia (rimonabant, manufactured by Sanofi-Aventis) is an anti-obesity drug that was supposed to be a big hit in the U.S. However, earlier this year, U.S. FDA decided not to approve the drug here in the states because the drug was found to increase suicidal thoughts and depression. Acomplia is, however, approved and available in Europe. This week, medical journal The Lancet published a review of clinical trials involving Acomplia to look at the safety and efficacy of this drug.

According to the review analysis (a meta analysis) of 4 past clinical trials involving a total of over 4100 patients, Acomplia did reduce more weight after 1 year of treatment than placebo. However, patients taking Acomplia were more than twice as likely as patients taking placebo to stop treatment because of depression. More anxiety was also seen in the Acomplia treatment group than in placebo. Even though patients with a history or risk of depressive mood were excluded from clinical trials, the observation that depression and anxiety still arose when Acomplia was taken suggests that the drug increases the risk of depression of anxiety. The study researchers suggest that doctors should monitor patients taking Acomplia for these serious psychiatric side effects. Also reported by Reuters.

The Lancet 2007; 370:1706-1713
DOI:10.1016/S0140-6736(07)61721-8

Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials

Robin Christensen MSc a, Pernelle Kruse Kristensen BSc a b, Else Marie Bartels DSc c, Prof Henning Bliddal MD a and Prof Arne Astrup MD email address b Corresponding Author

Since the prevalence of obesity continues to increase, there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and improve comorbidity. We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant.

Methods
We searched The Cochrane database and Controlled Trials Register, Medline via Pubmed, Embase via WebSpirs, Web of Science, Scopus, and reference lists up to July, 2007. We collected data from four double-blind, randomised controlled trials (including 4105 participants) that compared 20 mg per day rimonabant with placebo.

Findings
Patients given rimonabant had a 4·7 kg (95% CI 4·1–5·3 kg; p<0·0001) greater weight reduction after 1 year than did those given placebo. Rimonabant caused significantly more adverse events than did placebo (OR=1·4; p=0·0007; number needed to harm=25 individuals [95% CI 17–58]), and 1·4 times more serious adverse events (OR=1·4; p=0·03; number needed to harm=59 [27–830]). Patients given rimonabant were 2·5 times more likely to discontinue the treatment because of depressive mood disorders than were those given placebo (OR=2·5; p=0·01; number needed to harm=49 [19–316]). Furthermore, anxiety caused more patients to discontinue treatment in rimonabant groups than in placebo groups (OR=3·0; p=0·03; number needed to harm=166 [47–3716]).

Interpretation
Our findings suggest that 20 mg per day rimonabant increases the risk of psychiatric adverse events—ie, depressed mood disorders and anxiety—despite depressed mood being an exclusion criterion in these trials. Taken together with the recent US Food and Drug Administration finding of increased risk of suicide during treatment with rimonabant, we recommend increased alertness by physicians to these potentially severe psychiatric adverse reactions.

Affiliations
a. The Parker Institute, Musculoskeletal Statistics Unit, Frederiksberg Hospital, Frederiksberg, Denmark
b. The Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark
c. Copenhagen University Library, Copenhagen, Denmark