GLAXOSMITHKLINE: DEADLY DEPRESSING

February 2, 2005

http://www.orlandoweekly.com/news/Story.asp?ID=4817

GlaxoKline, Paxil and selective serotonin reuptake inhibitors (SSRIs):

It was the story that foreshadowed and strikingly paralleled the controversy

surrounding Merck, Vioxx and -2 inhibitors.

With the antidepressant Paxil (generic name paroxetine), the story was

driven primarily from the United Kingdom, by the BBC program Panorama and a

public interest group called Social Audit. They called attention to the

severe side effects from the drugs - notably, that they are addictive and

lead to increased suicide rates in youth.

In 2003, the evidence of dangerous side effects had piled too high for

British regulators to continue to ignore them. In June, the U.K. health

experts advised that children should not be prescribed Paxil.

In February 2004, Panorama reported on internal documents from

GlaxoKline (GSK) showing the company knew that Paxil could not be

proved to work in children.

In March 2004, days after the Medicines and Healthcare Products Regulatory

Agency (the United Kingdom's drug regulatory agency) advised that Paxil

dosages should be kept to low levels, an expert participating in the Paxil

review resigned, claiming the agency had possessed evidence for more than a

decade suggesting that Paxil dosages should be kept low, but failed to act

on it.

By this time, the story had started to heat up in the United States. Dr.

Mosholder, of the FDA Office of Drug Safety, had conducted an

analysis of clinical trials related to antidepressant use in children, and

found a heightened risk of suicide. But his superiors refused to let him

present his findings to an advisory panel convened to look at the issue in

the wake of the British action.

According to an investigation by Sen. Grassley, R-Iowa, the FDA

actually tried to get Mosholder to present data that deceptively

underrepresented the risk.

Although Paxil is not approved by the FDA for prescription to children,

doctors routinely write " off-label " prescriptions for the product for

children, a practice permitted under FDA rules. More than two million

prescriptions for Paxil were written for children and adolescents in the

United States in 2002.

In April 2004, The Lancet, the prestigious British medical journal,

published a paper showing that clinical test data did show problems with

prescribing Paxil and other SSRIs to children.

In June, New York State Attorney General Eliot Spitzer filed suit against

Glaxo, charging the giant drug maker with suppressing evidence of Paxil's

harm to children and misleading physicians. Spitzer's complaint cited a 1998

GSK memo which states that the company must " manage the dissemination of

these data in order to minimi[z]e any potential negative commercial impact. "

GSK responded in a statement that it " acted responsibly in conducting

clinical studies in pediatric patients and disseminating data from those

studies. All pediatric studies have been made available to the FDA and

regulatory agencies worldwide. " Responding to Spitzer's suit, GSK claimed

that, " As for the 1998 memo, it is inconsistent with the facts and does not

reflect the company position. "

In August, the company settled with Spitzer for $2.5 million, plus a

commitment to maintain the policy of posting clinical trial results, for all

drugs marketed by the company.

In October, the FDA ordered Glaxo and other SSRI makers to include a " black

box " warning with their pills. The warning says SSRIs double the risk of

suicide in children, though some medical researchers say the number should

be higher. Glaxo continues to insist that it disclosed information to

appropriate authorities as soon as it discerned important results from its

clinical studies.

February 2, 2005