What's in a Warning?
By SHERRY F. COLB
|Wednesday, Apr. 21, 2004|
A House committee is currently investigating the Food and Drug Administration ("the FDA" or "the Agency") for allegedly muzzling one of its scientists, Dr. Andrew Mosholder, who has expressed the view that the use of antidepressants is linked to suicide in children. His view is based on an analysis of drug companies' research comparing rates of suicide and suicidal gestures among depressed children taking antidepressants versus placebos.
Dr. Mosholder's conclusions depart from those of the Agency and the majority of its scientific advisors at this time. But if his conclusions were ultimately accepted, they would lead - at a minimum - to an FDA requirement that a warning label be placed on antidepressants, revealing the link to parents who purchase the drugs for their children.
FDA officials discouraged Dr. Mosholder from presenting his conclusions at a February public meeting of the Agency's Advisory Committee. Reportedly, they did so out of a fear of conveying the impression that his views represented the Agency's formal position.
The Point of Warnings
Even medications that have been approved as safe are ordinarily associated with some undesirable but unavoidable side effects or the risk of such side effects that must accordingly be revealed to consumers, in the form of a warning. (The same is true for surgical procedures and other medical interventions.) In a typical television advertisement for a medicine that treats allergies, for example, viewers hear a (quieter and more rapidly read) list of medical harms that may befall those who choose to take the medication.
Providing warnings for medical interventions serves a number of objectives. First, individuals have a right to give or withhold their informed consent, and part of what it means to be "informed" is to know not only the potential benefits of an intervention, but also the risks. By telling a patient of both the good and the bad that may come from taking a particular medicine, the relevant health professional or pharmaceutical company facilitates the patient's exercise of autonomy.
If a proposed surgical procedure, for example, will excise a tumor but may impair the patient's ability to sing, then an opera singer may choose to forego the procedure and thereby allow her own values to influence her choice of treatment. Similarly, a patient can choose to leave his cancer untreated because the available medicines will lengthen his days only by making them painful and nauseating.
Ideally, when a fully informed patient consents to a course of treatment, then, she takes charge of her life and weighs competing values in a manner that no one could do effectively in a state of ignorance.
A second purpose for warnings is to allow members of an especially high-risk subclass of patients to identify themselves and avoid the medication in question. Birth control pills, for example, may carry a risk of fatal blood clots for any patient who uses them. However, women over 35 and smokers might be at a higher risk for such clots than others in the population. Women who fall into this category might therefore choose not to use the birth control pill at all or to quit smoking before doing so -- and their doctors may, by the same token, avoid prescribing the birth control pill to them.
In this sense, warnings serve both to separate potential patients into different subclasses, based on the relative safety of medicines, and to help patients avoid activities that are contra-indicated.
The Risk of Warnings
Like the medications about which they warn, warnings themselves carry some risks. First, patients may be so frightened of the potential side effects of an intervention that they refrain from taking a useful medicine from which they would have benefited substantially. (Put another way, unlike the presumptively rational patient who calculates the weight of risks and benefits against the background of her own value set, an actual patient may focus so much on the risks of treatment that he fails to appreciate fully the potential costs of having no treatment at all.)
A second risk of warnings is that they will overwhelm the patient into passively accepting the recommendation of his physician. If a long list of hazards is read to a patient, it may eventually become difficult if not impossible to integrate each risk and assign it its proper value.
Sometimes, in other words, having too much information can be as disabling as having too little information. The difference is that with too much, a patient may experience the illusory feeling of having made a decision (one that he perhaps lives to regret) because he did, after all, receive warnings.
Antidepressants and Suicide
How do the purposes and risks of warnings translate when it comes to the potential for suicide among children who use antidepressants? Not especially well.
Consider by contrast the case of the opera singer facing surgery to remove a tumor - a case that pits the patient's desire to minimize the odds of her cancer recurring, against her desire to avoid the possibility of losing her voice. Unlike in this case, the parent of a patient in need of antidepressants faces two versions of the same risk. On the one hand, the child will, if left untreated, continue to suffer from depression, a mental illness that, left untreated, carries a serious risk of suicide. On the other hand, the child can take a medicine that may increase the chances of suicide but may also improve his condition and allow him ultimately to avoid suicide.
In this scenario, there is thus no real opportunity to allow one's competing values to determine the course of treatment. If another treatment plan, perhaps an alternative antidepressant, were effective but did not carry a risk of suicide, then the values competition might have a role to play -- particularly given the likelihood that alternative treatments would carry distinct side effect profiles that might have led doctors to avoid prescribing them to children in the first place.
As to the second purpose of warnings, it does not appear that we can know in advance of particular patients' using an antidepressant, which patients are likely to become suicidal as a result. Indeed, the determination of causation may be difficult even in those patients who do commit suicide, precisely because this risk is associated with both the disease and the cure. For parents trying to protect their children who suffer from depression, then, the knowledge that antidepressants can cause suicide will not give them guidance on whether or not their child ought to be avoiding the medication.
There is one respect, however, in which warnings can be useful in the prevention of suicide among those who take the medicine. Doctors who prescribe antidepressants can make sure to monitor their patients closely and watch for agitation and other indicators of potentially suicidal inclinations. When a person is preparing to commit suicide, there are often warning signs that a professional is equipped to detect.
To the extent that a general practitioner or pediatrician simply prescribes antidepressants without monitoring or even knowing how to monitor for suicide risk, the warning could have the salutary effect of motivating such a doctor to send her patient to a mental health professional, rather than simply writing a prescription for an antidepressant without further supervision.
As to the risks of warnings, it scarcely needs stating that if a parent is terrified of a child's committing suicide, that parent could make a terrible mistake by denying the child potentially life-saving treatment in the form of antidepressants. Learning that taking a drug may be lethal - whether the fatality is self-inflicted or not - can be quite scary, and there is a substantial risk that the person hearing about the potential lethality of a drug could be distracted from the reality of the underlying disease. If that were to happen, then the warning could lead to more deaths than it avoids.
And finally, there is the risk of passivity in the face of too much information. The parent who hears about the risk of suicide might be overwhelmed and simply direct the doctor to do what he thinks is best.
In such a case, the parent may feel that she has made a decision when, in truth, she has simply shut down in the face of threatening facts. If the risk of the child's suicide ultimately does come to pass, she may therefore be left unfairly blaming herself.
How Rational Are We?
The utility of warnings -- about antidepressants and other interventions -- seems to turn, at bottom, on the degree to which actual patients and their parents truly resemble rational calculators who weigh risks and benefits against each other and make decisions that are best suited to the patients' values.
In the case of suicide risk from taking antidepressants, it may turn out that warnings do more harm than good -- because they decrease drug-induced suicides only by increasing the number of suicides due to depression, over time, to a greater extent.
Given this risk, it may well be that the FDA was justified in attempting to prevent the premature public dissemination of the disputed scientific view that children who take antidepressants are at an elevated risk for suicide. In making its assessment, the House Energy and Commerce Committee should accordingly take care not to neglect the fact that warnings, like medicines, can have serious detrimental side effects.