Risks outweigh the benefits

OBESE PATIENTS in the Republic have lost a potentially useful weapon in the fight against the condition

OBESE PATIENTS in the Republic have lost a potentially useful weapon in the fight against the condition. That's the response of consultant endocrinologist Dr Donal O'Shea to the news that the anti-obesity drug Acomplia - used by about 3,000 people in Ireland - was being temporarily taken off the European market by manufacturer Sanofi-aventis because of a risk of psychiatric side effects.

"I was disappointed when Acomplia was withdrawn because it was a new class of anti-obesity medication," says O'Shea, who directs the State's largest public weight management clinic at St Columcille's Hospital in Loughlinstown.

Unlike other anti-obesity medications on the market, Acomplia targets "cannabinoid" (CB1) receptors in the brain that are involved in regulating food intake. By blocking the receptors, the drug can help patients lose weight, but possible side effects include depression, aggression and anxiety. It has been on the Irish market since 2006.

"In the first few months that [Acomplia] was out we had certainly seen a lot of psychiatric issues, but people fairly rapidly stopped using it if there was any hint of a problem. And we avidly warned patients if they got moody to stop taking it," says O'Shea, who is an associate professor of medicine at University College Dublin. About 47 suspected adverse drug reactions to Acomplia have been recorded in Ireland since 2006.

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However, when combined with positive changes in diet and exercise levels, some obese patients did very well on the drug, notes O'Shea. "We have seen patients who have gone down 20-25 kilos on Acomplia when they had been struggling along with great difficulty before that. It's also particularly good in people with diabetes where weight is an issue, it's helpful. And it's a pity to lose that weapon, even it is for a select group."

Patients on Acomplia will no longer have prescriptions filled in Ireland, but they should have no concerns about stopping the drug cold, says O'Shea.

"For a weight-reducing tablet there won't be anything rapid or sudden if they stop it," he explains. "But if it has been particularly helpful for them, they will have to fight extra hard to keep the weight they have lost off."

On a wider scale O'Shea believes the suspension of Acomplia sales will stop other drug companies from developing CB1-blockers for use in tackling obesity.

"It has sunk a new class of drug," he says. "Up until last month we had three agents that had been properly trialled over prospective two-year studies and beyond, and it looked like obesity was getting a proper spectrum of therapies. This is a setback to that."

And he reckons it could have been avoided. "One of the things that's disappointing about Acomplia is that if the company had been more limited in the initial licence and excluded people with a history of depression then I think we would still have it," he says.

"The problem is that it takes so much money to develop a drug now that companies need to target the biggest possible market, and excluding depression for a drug for obesity would take out a lot of your potential patients."

But while O'Shea believes that anti-obesity medication combined with lifestyle change can substantially help suitable patients who are overweight or early obese, not everyone is disappointed to see Acomplia go.

"In general for me are a last ditch option and I would discourage them greatly in the practice when people come in looking for them," says Louth-based GP Dr Harry Barry, author of Flagging the problem: a new approach to mental health.

He prefers instead to target the psychological issues that may lie at the root of overeating. "I ask all patients who are overweight - what they are eating, when they are eating and why they are eating. And I would spend most of my time on the third,'' he explains.

"My big problem with using these drugs is that it's like the quick fix -'I am not prepared to really take on the big issues in my life like why am I eating so much to start with, what's the pattern in my house. And if I don't really deal with that then I am not going to move on.'

And in my experience, most of the people who use these kinds of drugs a lot of the time will lose a certain amount of weight, eventually they will come off them and then within six months they will be back to where they were.

Tonight in an Irish Times/RDS Ireland in 2030 lecture in association with the Institute of Biology of Ireland, Prof Niall Moyna of DCU and Prof Donal OShea of UCD will jointly present a talk at 7pm at the RDS Merrion Room entitled Obesity- Treating the Epidemic, Preventing the Pandemic. For free admission tel: 01-2407289 or e-mail science@rds.ie

'Patients taking Acomplia should stop treatment and visit their GP'

Last month three anti-obesity medications were available on prescription in Ireland. Now there are two.

The newest of the drugs, Acomplia, was introduced in 2006. It blocks a type of receptor in the brain involved in hunger signals and so helps to suppress appetite.

However, the medication also has the potential for side effects including depression, anxiety and aggression.

As new data came to light, the European Medicines Agency (EMEA) added extra warnings, but finally decided last month that the benefits of Acomplia in helping patients lose weight and improve blood sugar control no longer outweighed the potential risks.

In international studies involving about 36,000 patients, five suicides were reported among patients taking the drug, compared with one reported suicide on a placebo regime, according to the EMEA.

"As a precautionary measure to protect patient health, this product will no longer be available," said Dr Joan Gilvarry, director of human medicines at the Irish Medicines Board, in a statement.

"Patients currently taking Acomplia should stop their treatment and visit their GP at their convenience for further advice."

Two other anti-obesity medications- Reductil and Xenical - remain on prescription in Ireland and have different modes of action in the body than Acomplia.

However, just as news of Acomplia's demise was filtering through, two other anti-obesity medications appeared on the European horizon. A positive opinion from the EMEA on GlaxoSmithKline's weight-loss boosting drug orlistat (currently sold over the counter as Alli in the United States) has prompted estimates that it could be on sale in Europe by 2009. And a report in The Lancet highlights the success in human trials of the drug tesofensine, manufactured by Danish company NeuroSearch, which acts on the brain to make patients feel full early in a meal.