To the Editor: Dr Pi-Sunyer and colleagues1 reported the results of the RIO-North America trial on the efficacy of rimonabant for weight loss. In this study, patients who received 20 mg of rimonabant daily had a 2.7-fold higher rate of psychiatric disorders (leading to early withdrawal or removal from the study) compared with those receiving placebo. Psychiatric adverse events have accounted for about half of all early terminations attributed to adverse events with the 20 mg of rimonabant dose in all RIO trials published to date. In the RIO-Europe trial,2 of the 14.5% of patients who withdrew early during treatment with 20 mg of rimonabant daily, 7.0% were attributed to psychiatric adverse events. In the RIO-Lipids trial,3 psychiatric adverse events accounted for 7.5% of patients withdrawing early during treatment with 20 mg of rimonabant daily, whereas only 2.3% withdrew in the placebo group for the same reasons (a 3.3-fold increase in risk with rimonabant).
In all of the RIO trials, depression and anxiety symptoms were monitored with the Hospital Anxiety and Depression scale. Depressive and anxiety symptoms are scored separately, with scores of 0 to 7 considered as within the normal range, 8 to 10 suggesting borderline symptoms, and 11 or higher suggesting probably significant symptoms.4 Although the eligibility criteria reported in the RIO studies did not mention a specific Hospital Anxiety and Depression score at which patients were excluded, the participants in these trials had a mean subscore for depression of approximately 3, suggesting that efforts were made to enroll individuals with minimal or no depressive symptoms. Furthermore, at least 1 of the 3 RIO studies noted that patients with a Hospital Anxiety and Depression score of 11 or higher during the study had to be referred to a psychiatrist.2 However, none of the 3 articles reported how many patients were removed from the studies following referral to a psychiatrist.
The prevalence of depression is high among obese persons seeking treatment.5 The question then is whether the psychiatric safety data of rimonabant presented in the reports of the RIO trials can be generalized to real-life clinical practices in which most obese patients are likely to have a Hospital Anxiety and Depression scale subscore for depression far higher than 3.
There is evidence suggesting that CB1 knockout mice demonstrate depressive state and that the CB1 blockade might induce depression.6 There is not sufficient evidence from the RIO trials to determine whether rimonabant is safe for use in obese individuals with even mild depression.
Financial Disclosures: Dr Gadde reported receiving research support from Vivus, GlaxoSmithKline, Eli Lilly, Elan, and Johnson & Johnson pharmaceuticals; reported being a consultant for Vivus and Orexigen; and reported owning stock in Orexigen.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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