Sunday Times 19th December 2004.

Fight to prove acne drug caused suicides

JOHN BURNS

A BUSINESSMAN whose son committed suicide while taking the acne treatment Roaccutane has spent almost 500,000 on independent research to try to prove that the drug causes depression.

Grant is using the research in his legal action against Roche Pharmaceuticals, the drug's manufacturer, in the hope of forcing it to admit liability. Grant is one of hundreds of people worldwide who believe that family members killed themselves because of the side effects of Roaccutane, a "last resort" drug for severe acne that can be prescribed only by consultant dermatologists.

His son, also called Liam, was a student aged 20 when he took his own life in 1997. His father claims that he had become seriously depressed after taking Roaccutane in the months before his death.

In the same year Seumas Todd, the 20-year-old son of Richard Todd, the actor, also committed suicide after taking the drug. His father said Seumas became depressed after taking Roaccutane and he believes that it was "undoubtedly" a factor in his death. An inquest in October heard that Jon Medland, 22, a medical student at Manchester University, hanged himself earlier this year after being prescribed Roaccutane.

Leonard Gorodkin, the Manchester coroner, called for the drug to be investigated. Grant has sold properties that were intended to be his pension fund to finance his research. "I realised that the only way studies on Roaccutane were ever going to be undertaken was if I personally commissioned and financed them," he said.

"I engaged experienced scientists to identify what precise studies were needed and I commissioned the most relevant. "I had to sell two properties to finance the studies; money readily spent in the name of my wonderful son Liam who I know with certainty would still be alive today if he had not taken Roaccutane."

Grant hired J Douglas Bremner of Emory University hospital in Atlanta to check what effect the anti-acne drug had on the brain. Bremner's preliminary finding was that those who took Roaccutane showed decreased activity in the orbitofrontal cortex, a brain area thought to control mood and social interaction. Brain scans showed that acne patients who took antibiotics instead showed no change.

Dr Peter McCaffery, from the University of Massachusetts Medical School, was commissioned to study 13-cis retinoic acid, the active ingredient of the drug, and found that it reduced cell proliferation in the brains of mice and disrupted their capacity to learn spatial maze tasks. Grant plans to use this to show that the drug has a detrimental effect on the brain.

The court case being heard in Dublin seeks damages for the distress suffered by Grant because of the loss of his son as well as demanding an admission of liability. Grant has already turned down an ex gratia offer to drop the case in return for compensation that would have cost Roche up to 800,000. In an open letter to Grant and without admitting liability, Roche's lawyers offered to settle the case "having regard to the enormous costs and resources which would be involved in fighting the litigation and the length of time that a trial would take".

The drug firm, which is based in Switzerland, was offering him a sum equivalent to the amount he might have won in an Irish court, along with special damages and costs.

However, Grant believes that Roche offered to settle to avoid handing over its own research documents in court. A pre-trial deposition in a lawsuit against Roche in Florida heard that one of the company's doctors recommended that users of the drug be monitored for signs of depression. A spokesman for Roche said that it had offered to settle the case in order to avoid lengthy and distressing litigation.

It said that about 13m people have been treated with Roaccutane since it became available more than 20 years ago. "It is a well tolerated and effective medicine which means we have no option but to dispute the claim Mr Grant made," the spokesman said. "We continue to have the fullest confidence in the drug."

Roche disputes Grant's estimate of his costs and its lawyers are to make an application to the High Court in Dublin next year to have the case struck out on the basis that they have already offered a sum equivalent to the highest amount he might have won. Grant says he will settle only in return for an admission of liability. Several high-profile suicides in America have been blamed on the drug. The teenage son of Bart Stupak, a Democratic congressman, killed himself in 2000 while taking Accutane, the American brand name for the medication. Following a political campaign led by Stupak, government rules for the drug were tightened recently.

In January 2002 Charles Bishop, 15, killed himself when he crashed a plane into a 42- storey Bank of America building in Tampa. Florida. Police were said to have found a prescription for Accutane in Bishop's home, but the coroner found no trace in his system. Bishop's family is suing Roche.

In Britain the Department of Health is considering a request that it undertakes an examination of the medical records of up to 6,000 people a year who committed suicide over the past two decades to establish how many of them used Roaccutane. Campaigners against the drug believe that the exercise would demonstrate a strong link between use of the drug and suicide.

However, a British firm of solicitors that received legal aid to pursue litigation against Roche five years ago has now dropped the actions, believing that the cases would be impossible to prove. "About 80 or 90 claimants came forward but we had to report that we did not think the claims could be won," said Mark Harvey, now a partner in Hugh James, the solicitors in Cardiff. "You have to be able to link depression to the drug and it would be difficult to prove that it might not have arisen anyway and to eliminate other causes. Isn't depression a side effect of puberty or acne in any event? It is going to be difficult to get the Legal Aid Board to reopen this."