IN THIS ISSUE:
December 2010

Asenapine: More Data
Olanzapine (Zyprexa) may be better tolerated and more efficacious for patients with bipolar I disorder than asenapine (Saphris).

Sibutramine (Meridia and others): Risks versus Benefits
After a large trial found a higher frequency of adverse cardiovascular events in sibutramine- versus placebo-treated patients, this "diet pill" was withdrawn from the US market.

Antidepressants and Weight Gain
While some antidepressants have no significant effect on body weight, many may cause weight gain or loss during short- or long-term treatment.

In Brief
Psychiatric Disorders Associated with Suicide Attempts in Prisoners; Buprenorphine Implants for Opioid Dependence

Bupropion for Smoking Cessation in People with Schizophrenia
In smokers with schizophrenia, bupropion (Wellbutrin, Zyban, and others) increases the odds of abstinence.

2010: Close and Save
Dr. Gelenberg's end-of-year editorial and holiday message.

INDEX
2010 Index

Sibutramine (Meridia and others): Risks versus Benefits

December 2010

In October, we reviewed lorcaserin and the history of medications to help people lose weight (BTP 2010;33:40-41). The rationale for "diet pills" rests for the most part on the adverse physiologic effects of excess body weight. Presumably, weight loss from a medication should improve long-term health outcomes. But a recent pharmaceutical company-funded multicenter trial came to the opposite conclusion.1

Abbott Laboratories, the manufacturer of sibutramine (Meridia and others), conducted a large study called Sibutramine Cardiovascular OUTcomes (SCOUT).1 SCOUT was designed to determine the effects of sibutramine-aided weight loss on cardiovascular events among high-risk subjects.

More than 10,000 overweight or obese individuals, aged 55 years or older, with preexisting cardiovascular disease or type II diabetes mellitus were enrolled in this trial. In addition to participation in an individualized diet and exercise program, subjects were randomly assigned to receive placebo or the serotonin norepinephrine reuptake inhibitor sibutramine. The mean duration of treatment was 3.4 years. During a 6-week single-blind lead-in period, subjects lost an average of 2.6 kg (5.8 lb). After randomization, subjects who received sibutramine achieved and maintained an additional loss of 1.7 kg (3.8 lb) on average. At 12 months, sibutramine-treated patients had lost an average of 4.3 kg (9.6 lb), but during the remainder of the study, they regained roughly 0.5 kg (1.1 lb). At 12 months, the average weight loss with sibutramine was 4.5% of initial body weight.

A worrisome finding from the SCOUT trial was the higher frequency of cardiovascular events (myocardial infarction [MI] and stroke) in sibutramine-treated patients (11.4%) than in the placebo group (10.0%; P = .02). Patients with diabetes but without preexisting cardiovascular disease did not show an increase in cardiovascular events, but patients with diabetes and cardiovascular disease had more nonfatal MIs and stroke when treated with sibutramine.

In an editorial accompanying the SCOUT paper, Curfman and others suggest that the risk-benefit ratio does not justify sibutramine remaining on the market.2 They observe that the number of patients needed to be treated to cause one cardiovascular event is 70, and among patients with known cardiovascular disease, the number needed to harm declines to 52. In their opinion, the < 4 kg (8.4 lb), 4.5% weight reduction brought about by sibutramine does not justify the elevated risk of an MI or stroke.

In our earlier article, we observed that sibutramine-containing medications had recently been removed from the European market. The US Food and Drug Administration (FDA) had recommended that labeling for sibutramine advise patients with a history of cardiovascular disease not to take it. In September, half of the FDA's Endocrinologic and Metabolic Drugs Advisory Committee recommended that sibutramine use be further restricted, while the other half recommended that the agent be withdrawn.3 A few weeks later, Abbott announced that they were voluntarily withdrawing sibutramine from the US market. The search for a "diet pill" that delivers on its promises continues.

1James WP, Caterson ID, Coutinho W, Finer N, Van Gaal LF, Maggioni AP, Torp-Pedersen C, Sharma AM, Shepherd GM, Rode RA, Renz CL: SCOUT Investigators: Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects. N Engl J Med 2010;363:905-917.

2Curfman GD, Morrissey S, Drazen JM: Sibutramine-another flawed diet pill. N Engl J Med 2010;363:972-974.

3Redmond C: FDA-approved weight loss drug: Panel suggests Meridia withdrawal. Available online at http://www.suite101.com/content/possible-withdrawal-of-fda-approved-prescription-weight-loss-drug-a286838. Accessed October 4, 2010.