There are an interesting series of news articles available lately (the Yahoo Mental Health News page is a good place to view them) that cover the evolving controversial over the proper regulation and labeling of antidepressant medications as prescribed for children. The stories illustrate how the American drug regulation process works and doesn't work to protect end users of medications.
Pharmaceutical companies spend small fortunes on drug development, gambling that their investment in the creation of a new compound and the patents they receive for the molecules and manufacturing processes they develop will enable them to reap big profits. Profits are not an option for these companies until drugs can be marketed, however. In the United States, a new medicine must be shown to be effective and safe before it will be allowed to be marketed. The government agency charged with the task of regulating medications in the United States is the Food and Drug Administration or FDA.
Pharmaceutical companies want to make quality medicines that will be genuinely helpful in solving medical problems. They also want to make large profits. These two goals are somewhat at odds with each other. Profit motives tend to push companies towards an action bias; towards getting to market sooner rather than later. Quality motives, on the other hand, push companies towards carefulness and precision; towards spending the time and money necessary to demonstrate the safety and efficacy of their products. Although both goals are real forces within these companies, let's face facts that these motives are not equivalent in strength. In this world, profit pressures invariably will trump quality pressures. As I understand it, what ends up happening is that pharma companies comply with FDA mandated testing (as they must by law in order to sell in the USA), but don't as a rule volunteer further data or study that might risk them their market access. This behavior is understandable in many respects. There is a genuine competition and profit motivation that pushes these companies to develop new medicines. Without the promise of profit, they wouldn't be as motivated to do research and development, and the pace of new drug development would probably slow. Recognizing this market reality, the system is set up so as to work with the FDA in an adversarial role as protector and defender of the people. It is up to the FDA to be the force for quality and safety. This system can only work right if the FDA is incorruptible, however. Given our present business and political climate, who can blindly assume that this is the case? Although we can't know for sure, we'll give them the benefit of the doubt, and assume that the good folks at the FDA do their best to protect the public with regard to new medications coming onto the market.
All with the best of intentions, the FDA says to many different manufacturers of new antidepressant drugs, "prove to our satisfaction that your product works and is safe". The different drug manufacturers then go out and do studies to produce this required evidence to the FDA's satisfaction. In most cases, however, the drug companies have only applied to the FDA for permission to market the drugs in question to adults, and in response, the safety data the FDA mandates the pharma companies to produce is only focused on whether the drugs in question are safe for adults. Assuming this bar is passed, the drug can then be marketed - to be used as an adult treatment. No problem so far, right?
Well, maybe there is a problem. So far as I know, however, physicians have traditionally been free to prescribe drugs outside of the narrow confines the FDA approves them for. In this case, as I understand it, physicians are free to use the antidepressant drugs labeled safe for adults, with the very young and the very old. The FDA knows this, of course, but does not mandate that safety testing be done for all persons. There is a problem here, I think. One that would be difficult to fix without on the one hand, reducing physician's freedom to treat according to their best training, or on the other hand placing a far higher and more stringent burden on the drug companies to prove the safety of their products (which might reduce innovation). What to do?
It is simply not a safe assumption to make that if a drug is safe for an adult that it will be similarly safe for children and the elderly. It is well known by physicians that how old a person is, how much they weigh, and other similar factors have a real bearing on how a drug will affect that person. Drug doses that work find on a 30 year old skinny person, might not work the same way on a 30 year old chunky person. Drug doses that work on a 30 year old person of any weight might not work well on a young child, or on an older person. There are differences in how drugs are metabolized by different people and these must be respected if the drugs are to be used safely.
It seems that at least some of the popular antidepressant drugs ruled to be safe for adults lead to an elevated incidence of suicidal behavior in children. This effect is not huge - perhaps 2 or 3 children are at risk out of every 100 treated, and being at risk doesn't mean actually attempting suicide - but the idea of putting any child at risk is abhorrent. Ethics would seem to demand that these drugs be prohibited for use with children. Except that this is not necessarily a great policy either, because if these drugs are pulled from use, some children who might have benefited from them will not get them and they may then be at elevated risk for suicide and unnecessary dysfunction. What is needed is a middle path.
This stuff is in the news right now because the FDA took a very long time (some say unnecessarily and unethically long) in determining that there was a real problem and deciding to do something about it. According to one news report, Dr. Andrew Mosholder, an FDA epidemiologist, determined that there was a real risk but FDA superiors asked him to suppress the findings in a 2003 report to congress. There was a governmental hearing meeting on the subject in February, 2004 and the FDA released this FAQ in March,2004. However, at that time the data were presented as tentative near as I can tell. The findings were not confirmed and made public until a few weeks ago in early Fall, 2004. We're talking months and months between when the government knew there was a serious risk to the health of millions of kids and when they decided to do something about it. You'd think this sort of thing would be fast tracked ...
The FDA says they were being careful to get the facts right before making them public. This seems plausible to me actually. But then again, it's also kinda disturbing that the FDA would be sitting there disbelieving what their own qualified people are saying. How much evidence do you really need actually to recommend an enhanced warning when young lives are at unnecessary risk? It smells bad that they'd sit there waiting for confirmation when they might be able to reduce risk to children by acting quickly.
In this case with the antidepressants, it's fairly easy to jump to conclusions that the FDA was stonewalling and hiding evidence based that might have saved lives. Some Congresspersons and physicians are thinking just this, apparently, and it may be true, for all we know. Then again, there may be no malice. Regular old bureaucratic inefficiency is perfectly capable of accounting for this as well. At this point in time, it simply is not clear.
The good news is that the FDA is apparently going to do something about their recently released findings. They plan to update the labeling on antidepressants (Prozac, Paxil, Wellbutrin, Zoloft, Celexa, Effexor, Luvox, Remeron, and Serzone, and generic forms of these drugs) so that it is crystal clear to prescribing physicians that young children could be at increased suicide risk if they are administered the medicines. This seems to be a reasonable outcome. Remember that these medicines do potentially have a lot to offer to the majority of depressed children. It is a minority of cases that are noted to have a dangerous reaction. When you have a case where a medicine could help AND hurt depending on the circumstance, it should be up to our highly trained physicians to make the judgment as to when the risks outweigh the benefits for any individual case. It seems reasonable that the FDA should at the very least, make it clear to all physicians that they must prescribe with great care, however.
The FDA has even announced that they will begin a study to find out if the same medicines are possibly associated with suicide risk in adults. You would think they would already have been studying data on this possibility, as the antidepressant drugs in question are already approved for use with depressed adults, and because suicide is a well known symptom of depression. Oh well.
All of this just goes to show you what can get done when enough attention gets focused on an issue ... and also how little can get done when the spotlight is not glaring.