Rimonabant: perspectives and controversies

LETTER TO THE EDITORS

Rimonabant: perspectives and controversies^*

Karine Zortéa, Rafaela Festugatto Tartari

Nutritionist.

Dear Editors,

Cardiovascular diseases are a public health problem, accounting for more than 30% of worldwide deaths.¹ Diabetes, hypertension, smoking and occurrence of new risk factors (increased abdominal circumference and dyslipidemia) are known to contribute to global cardiovascular risk.² The American adult population has about 66% of overweight and 34% of obesity.³ In Brazil incidence is approximately 32% of overweight and 8% of obesity.⁴ As a consequence, specialists have been developing new conducts to treat/prevent such condition.

Attention to the therapeutical potential of substances interfering with the endocannabinoid system⁵ has been growing due to their role in the control of food ingestion and energy balance. This system acts on specific brain areas, such as the hypothalamus, and on peripheral tissues (adipocytes, hepatocytes, gastrointestinal tract, and skeletal muscle). Therefore, drugs (rimonabant) interfering with its action are promising in the treatment of many diseases, including obesity, dyslipidemia, insulin resistance, and atherosclerosis.⁶ Rimonabant has been approved in Brasil⁷ and Europe, but not in the USA.⁸ Large studies corroborated rimonabant efficacy, such as the RIO-Europe, RIO-North America, RIO-Lipids, and RIO-Diabetes. One year of treatment using rimonabant 20 mg/day, along with a hypocaloric diet and promotion of physical activity, caused reduction in weight and waist circumference, and improvement in HDL cholesterol, triglycerides, glucose, and insulin resistance. Although rimonabant is well tolerated, it may cause side effects, such as mood changes, depression, anxiety, dizziness, nausea and even suicidal ideation.⁹

The Strategy to Reduce Atherosclerosis Development Involving Administration of Rimonabant - the Intravascular Ultrasound Study (STRADIVARIUS) is another large study, conducted in North America, Europe and Australia, in which patients with cardiovascular diseases and abdominal obesity were given rimonabant 20 mg for 18 months. There was reduction in body weight, improvement in lipid profile, reduction in C-reactive protein levels and in glycosylated hemoglobin. However, side effects were also observed, such as depression, anxiety (43.4%) and cases of suicidal ideation; one patient using the medication committed suicide.¹⁰

Psychiatric side effects were the main concern of the Food and Drug Administration (FDA) against approval of rimonabant in 2007.⁸ Although studies report low rates of complications, a condition of depression and suicidal intention cannot be considered irrelevant. If there were cases such as these, and especially after a real case of suicide has been confirmed, professionals should be warned. Before prescribing such drug, the patient should be strictly assessed in terms of psychological conditions, so that a condition of depression is not worsened. Even so, a psychologically normal individual has the risk of developing a depressive condition caused by this medication. This manuscript aims at increasing awareness of health professionals to prevent indiscriminate use of rimonabant.

References

• 1. Strong K, Mathers C, Leeder S, Beaglehole R. Preventing chronic diseases: how many lives we can save? Lancet. 2005;366(9496):1578-82.
• 2. Cleeman JI, Grundy SM, Becker D, Clark LT, Cooper RS, Denke MA, et al. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486 -97.
• 3. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006;295(13):1549-55.
• 4. Sposito AC, Caramelli B, Fonseca FAH, Bertolami MC, Afiune NA, Souza AD, et al. IV Diretriz brasileira sobre dislipidemias e prevenção da aterosclerose: Departamento de Aterosclerose da Sociedade Brasileira de Cardiologia. Arq Bras Cardiol. 2007;88(S1):2-18.
• 5. Godoy-Matos AF, Guedes EP, Souza LL, Valério CM. O sistema endocanabinóide: novo paradigma no tratamento da síndrome metabólica. Arq Bras Endocrinol Metab. 2006;50(2):390-9.
• 6. Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev. 2006;27(1):73-100.
• ⁷
  Sanofi-aventis Laboratório. Acomplia^® (Rimonabanto) é aprovado no Brasil para o tratamento de pacientes obesos ou com sobrepeso com fatores de risco cardiometabólico associados como diabetes do tipo 2 ou dislipidemia. http://www.sanofi-aventis.com.br/live/br/pt/layout.jsp?cnt=A6FED1FE-9C3D-4E15-8161-F3FD54B6E606&strSelectView=CONTENT-NORMAL&strPageView=2 Acessado jul 2008.
• 8. Rumsfeld JS, Nallamothu BK. The hope and fear of rimonabant. JAMA. 2008;299(13):1601-2.
• 9. Van Gaal L, Pi-Sunyer X, Després JP, McCarthy C, Scheen A. Efficacy and safety of rimonabant for improvement of multiple cardiometabolic risk factors in overweight/obese patients: pooled 1-year data from the Rimonabant in Obesity (RIO) program. Diabetes Care. 2008;31 Suppl 2:S229-40.
• 10. Nissen SE, Nicholls SJ, Wolski K, Rodés-Cabau J, Cannon CP, Deanfield JE, et al. Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial. JAMA. 2008; 299(13):1547-60.

*

Nota dos Editores: Após o aceite desta carta, o rimonabanto foi retirado do mercado pela agência de regulação devido aos seus importantes efeitos colaterais. Apesar disso, decidimos manter a publicação, como demonstração de que tais comunicações dão suporte científico à prática clínica.

Publication Dates

• Publication in this collection
  17 Mar 2009
• Date of issue
  Dec 2008