I promised to be back with more links and here I am. Unfortunately, one of the best stories that I read about this was in the Wall Street Journal, which is not accessible on the Internet unless you subscribe. It went into detail about a presumed cover-up at the FDA.

In brief, the association between SSRI antidepressants and suicide has been a controversial topic since Prozac, the first drug in this class, was introduced. In 1991, an FDA advisory panel concluded that there was no association but questions continued to persist, particularly with pediatric patients. The FDA began an investigation of Paxil in late 2002, and the following June, issued an advisory to physicians which cautioned against its use in juveniles because of a possible increase in suicidal thinking. In October they broadened their advisory, stating that evidence from clinical trials showed that Paxil, along with several other SSRIs, was not any more effective than a placebo.

The Plot Thickens

While a number of recent studies have suggested an association between SSRIs and suicide in children, many of these trials were funded by the pharmaceutical industry and left unpublished. Andrew Mosholder, MD, an epidemiologist with the FDA, analyzed 22 studies involving seven antidepressants and over 4,200 children. He concluded that pediatric patients using SSRIs were almost twice as likely to become suicidal as those given a placebo. About the same time that Mosholder reached his conclusion, the Committee on Safety of Medicines in Great Britain banned the use of all SSRIs for patients under the age of 18 except for Prozac, the only one formally approved for this age group.

But Mosholder found himself with duct tape across his mouth. He was not permitted to present his analyses at the hearing on this, and critics accused the FDA of trying to conceal negative information and protect the drug industry. In a confidential report which was later leaked to the press, ie, the Wall Street Journal, Mosholder said that the FDA should follow the Britain’s lead and discourage usage of these agents.

FDA officials wrote in internal memorandums that Mosholder’s analysis was “unreliable,” and so hired researchers at Columbia University to essentially conduct the same research (good use of money, n’est-ce pas?). Much to the dismay of the FDA, I’m sure, the study out of Columbia reached an almost identical conclusion.

The Empire Fights Back

In April 2004, Rep. Joe Barton (R-TX), Chairman of the House Energy and Commerce Committee, issued the following statement upon receiving the Food and Drug Administration’s response to a March 24 letter from the committee seeking information on the use of antidepressants by children:

“Oversight and Investigations Subcommittee Chairman James Greenwood (R-PA), has been dogged in his pursuit of the antidepressant issue, and in response to our letter, the FDA admits important facts for the first time.

“FDA’s primary medical reviewer believed that the available data were sufficient to conclude an association exists between the use of antidepressants and suicidal behavior in children. He also recommended that action occur without further delay, although others at FDA disagreed with his recommendation. There are troubling questions of whether FDA supervisors inappropriately suppressed significant information that would have been of consequence to their own advisory committee, not to mention the public.”

About six months ago, the FDA did finally ask the manufacturers of 10 major antidepressant drugs to add a warning to drug labels about the risk of suicidal behavior, but many critics felt that they were doing too little too late. On the other side of the coin, other critics believed that the data linking suicide and SSRIs is weak and inconclusive, and there are too many other variables involved.

Anyway, some links. Here is a good one from the International Herald Tribune that tells a little bit about this saga’s history.

Another good article at the Post Gazette

NPR did a whole series of stories about this.

And last but not least, an interesting story from the American Medical Association’s AMNews which points out that an American College of Neuropsychopharmacology task force concluded that SSRIs do not increase teens’ risk of suicidal thinking or suicide attempts.

Image: Courtesy of Stock.XCHNG

After several years of debate, controversy, accusations that the FDA was dragging its feet and reluctant to move on this, antidepressants will now be bestowed with a “black box” warning. It is the strongest warning the United States can put on prescription drugs, and no drug company likes having to put one on–for obvious reasons. When you take medicine you like to think of the curative effects, not see a skull and crossbones glaring at you.

Okay, the black box warning is not quite skull and crossbones, but it indicates that there could be a severe reaction to a drug. In the case of antidepressants, the warning is that there may be an increased risk of suicide among teens and children.

The UK has banned the use of nearly all antidepressants in children and adolescents, save for Prozac, which is the only one that has been extensively tested in this population and declared not to raise the risk of suicide. The U.S. has not gone that far, as the new warning language does not expressively prohibit antidepressants from being prescribed in children and adolescents. It just warns that the danger exists.

Some say that this is more hype than science, and others say that the FDA is not going far enough. There were a number of stories about this, one notably in the Wall Street Journal. Sorry, don’t have a link to it–but here’s a short update that appeared from Reuters

I’ll check and see if there are any other good links, which give more of a history about this.