Evidence that potential blockbuster weight loss drug Acomplia (rimonabant) causes neurological and psychiatric problems and increases the risk of suicide has led to a unanimous vote against the drug by a US FDA advisory panel. Although rimonabant is already being marketed in 37 countries, it is now unlikely the FDA will approve the weight loss drug, to have been sold in the United States under the name ‘Zimulti’, without more positive data on safety.
The FDA advisory panel considered evidence (see the FDA briefing document, released yesterday) that highlighted the risk of numerous so-called ‘psychiatric adverse events’ and ‘neurological adverse events’, as well as seizures — but the primary safety concern raised by the evidence was the risk of suicidality. From page 59 of the FDA briefing document:
Compared to placebo, 20 mg rimonabant statistically significantly increased suicidality based on analyses both of incidence rates and person-years.
And in all 13 studies analysed by the FDA, the percentage of patients experiencing at least one psychiatric adverse event was higher for the group receiving rimonabant than for the control group (page 68 of the report); an even larger body of separate studies showed a higher incidence of both other neurological adverse events (of more than 3 dozen different types) and seizures.
The drug, which works on the brain’s endocannabinoid system, as discovered through research into marijuana, which works on brain receptors to give users the ‘munchies’. Rimonabant is thought to curb hunger by suppressing cannabinoid receptors. However, interfering with the system — which is also involved in the modulation of the HPA (hypothalamus, pituitary, adrenal) axis and is thus thought to play a role in depression, phobias, anxiety, and other disorders — apparently also increases the risk of the psychiatric adverse events highlighted by the research. (Several clinical trials are still recruiting participants.)
According to coverage in the New York Times, FDA staff medical reviewer told the FDA panel that the drug doubled a patient’s risk of problems like anxiety, depression, aggression and psychosis.
The European Medical Agency (EMEA) approved the drug in June 2006, according to the FDA briefing document — just 4 months after the FDA had demanded more safety information in February 2006 due to its initial concerns about suicidality and other adverse effects. It is now marketed in 3 dozen countries and available for purchase in Argentina, Austria, Denmark, Finland, Germany, Ireland, Norway, Sweden, Greece, and the United Kingdom.
The zaniest part of this all?
According to the briefing document, the actual weight loss effects of rimonabant are quite similar to those of other drugs already on the market, such as Xenical and Meridia: a roughly 5% loss, followed by a regaining of the weight.
And that’s only if you’re one of the lucky 1 in 4 or so who actually experience the weight loss effect.
Is it worth the risk of suicidality, depression, seizures, and more?