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Neuropsychiatric adverse effects signal the end of the line for rimonabant

Nature Reviews Cardiology volume 7, page 602 (2010)Cite this article

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In November 2008, the European Medicines Agency requested that all clinical trials of the selective cannabinoid-1 (CB1) receptor antagonist rimonabant be terminated with immediate effect following reports of serious neuropsychiatric adverse effects. CRESCENDO was one such study. The CRESCENDO investigators have now published the initial findings of this trial in the Lancet. Data collected before termination of the study indicate that rimonabant did not reduce the incidence of major cardiovascular events when compared with placebo, but was indeed associated with an increased risk of anxiety, depression, and suicide.

Rimonabant was the first selective CB1 receptor antagonist to be approved and used in clinical practice. Blockade of the endocannabinoid system carried high hopes as a pharmacological strategy for the treatment of obesity, which is a pandemic risk factor for cardiovascular disease. Over the past 5 years, clinical studies of rimonabant have shown beneficial effects in terms of weight loss, reduction in waist circumference, increases in levels of HDL cholesterol, and reductions in triglyceride levels and total atheroma volume. However, none of these studies demonstrated reductions in blood pressure or levels of LDL cholesterol (both major determinants of atherosclerotic progression) and, as early as 2007, an increase in the risk of psychiatric disorders associated with the drug was reported. CRESCENDO was the first randomized, placebo-controlled trial designed with the aim of evaluating the long-term effects of rimonabant on hard clinical end points (a composite of cardiovascular death, myocardial infarction, and stroke).

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ORIGINAL RESEARCH PAPER

  1. Topol, E. J. et al. Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial. Lancet 376, 517–523 (2010)

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  1. Alexandra King
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King, A. Neuropsychiatric adverse effects signal the end of the line for rimonabant. Nat Rev Cardiol 7, 602 (2010). https://doi.org/10.1038/nrcardio.2010.148

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  • DOI: https://doi.org/10.1038/nrcardio.2010.148

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