Patients given Rimonabant are at increased risk of severe psychiatric events.

The prevalence of obesity continues to increase worldwide, and there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and thereby reduce prevalence of conditions associated with being overweight.

Rimonabant is an anti-obesity drug. It is a CB1 cannabinoid receptor inverse agonist.
It is indicated for use in conjunction with diet and exercise for patients with a body mass index ( BMI ) greater than 30 kg/m², or patients with a BMI greater than 27 kg/m² with associated risk factors, such as type 2 diabetes or dyslipidaemia.

Arne Astrup, at University of Copenhagen, Denmark, and colleagues did a meta-analysis of four double-blind randomised controlled trials featuring 4105 patients, which compared treatment with 20mg per day Rimonabant with placebo.

They found that patients given Rimonabant had a 4.7 kg greater weight reduction after one year than did those given placebo. However, patients given Rimonabant were at 40% higher risk of having adverse events or serious adverse events.
Patients given Rimonabant were 2.5 times more likely to discontinue treatment because of depressive disorders than were those given placebo, and three times more likely to discontinue treatment due to anxiety.

The authors point out that there were no follow-ups after discontinuation of active treatment with Rimonabant, thus any weight regain could not be assessed. They say: "As with other weight-loss drugs, relapse is expected to occur after treatment has ended, and to achieve weight maintenance and maintain the improvement of the cardiovascular and diabetes risk factors the drug needs to be taken for life."

They conclude: " Our findings suggest that 20mg per day of Rimonabant increases the risk of psychiatric events ( ie, depressed mood disorders and anxiety ) despite depressed mood being an exclusion criterion in these trials. Taken together with the recent FDA ( 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."

In an accompanying Comment, Philip Mitchell and Margaret Morris, at University of New South Wales, Sydney ( Australia ), say: " These findings are especially striking since those with a history of significant depression or other psychiatric illnesses had been excluded before study entry; there is strong evidence that people with severe obesity are at high risk of depression -- [this] meta-analysis raises major questions about the safety of Rimonabant in obese people, who are already at an increased risk of depression, especially since the FDA review suggests that the risk of suicide is increased with this agent."

Source: The Lancet, 2007

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