Two overviews of trials of weight-loss drugs have added to concerns that the obesity treatment rimonabant may boost the risk of depression and anxiety.
The papers, published in Saturday's issue of The Lancet and online Friday by the British Medical Journal (BMJ), follow a decision in June by an advisory panel to the US Food and Drug Administration (FDA) that voted against marketing rimonabant in the United States on safety grounds.
Doctors led by Arne Astrup, a professor at the Faculty of Life Sciences at the University of Copenhagen, analysed four trials in which 4,105 patents were either given a 20mg daily dose of rimonabant or a dummy lookalike pill called a placebo.
Over one year, patients on rimonabant realised a weight loss that was 4.7 kilos (10.3 pounds) higher than counterparts in the placebo group.
But they were also 40 percent likelier to experience "adverse" or "serious adverse" events, according to Astrup's study, which appears in The Lancet.
Patients on rimonabant were two and a half times likelier to stop taking the drug because of depression than those on placebo, and three times likelier to discontinue the treatment because of anxiety.
The findings are significant because individuals with a history of depression -- a phenomenon common among the severely obese -- were specifically excluded from the trial, say the authors.
"We recommend increased alertness by physicians to these potentially severe psychiatric reactions," the Lancet paper says.
Meanwhile, a study published online Friday by the British Medical Journal (BMJ) said that rimonabant and two other anti-obesity drugs, orlistat and sibutramine, were of only limited effect in terms of weight loss over the long term.
Canadian researchers reviewed data from 30 trials in which obese volunteers -- average weight 100 kilos (220 pounds) -- took either anti-obesity drugs or a placebo for a year or more.
The three drugs reduced weight by less than five kilos (11 pounds), equivalent to a loss of less than five percent of total body weight.
The three drugs had various beneficial side effects but all had adverse effects, including, in rimonabant's case, an increase in depression and anxiety, they said.
The authors noted that no trials examined rates of death and disease as a result of taking anti-obesity pills and called for trials to looking into this aspect.
In June, all 14 experts on the FDA's Advisory Committee said rimonabant, which French maker Sanofi-Aventis had hoped would become a blockbuster drug under the brand name of Zimulti, voted against authorising the drug after they heard evidence that it was linked with an increased risk of suicide.
The European Union has approved rimonabant, locally marketed as Acomplia, as a support for diet and exercise for obese patients who have Type 2 diabetes and cardiovascular problems associated with obesity.
However, labelling of the drug has been stepped up to warn against prescribing it to European patients with depression or those taking anti-depressants.
A trial among 1,047 volunteers, published in The Lancet in October 2006, found ribonant improved control over blood glucose and blood fats among people with Type 2 diabetes.
The drug was "generally well tolerated," the study said. Among those volunteers who dropped out of the trial, depression, nausea and dizziness were the most cited reasons among the rimonabant group.
Rimonabant blocks endocannabinoid receptors in the brain that cause hunger.
Global sales of anti-obesity drugs reached 1.2 billion dollars in 2005, the BMJ said.