Dec 07 2012

Promoting Off-Label Use of Drugs

The off-label use of prescription drugs is often misunderstood by conflating it with the non-evidence-based use of drugs. I actually don’t have an issue necessarily with using drugs off-label. A distinct issue is whether or not drug companies can promote off label uses, and how they can advertise their drugs at all. A recent court decision may loosen restrictions on the pharmaceutical industry (and by extension the supplement industry and the marketing of any health product).

In a case that could have broad ramifications for the pharmaceutical industry, a federal appeals court on Monday threw out the conviction of a sales representative who sold a drug for uses not approved by the Food and Drug Administration. The judges said that the ban on so-called off-label marketing violated the representative’s freedom of speech.

The ongoing battle between regulation and free speech rages on. First for some background, in the US the FDA regulates the marketing of drugs, which are defined as a substance that is used to treat or modify any disease. Supplements are now defined as substances use to enhance or improve some structure or function in the body, but cannot be claimed to treat any specific disease. So these categories are based, for regulatory purposes, on the kinds of claims that are made for them.

Pharmaceutical companies must apply to the FDA for the right to study a potential new drug in humans, to meet the requirement for evidence of safety and effectiveness to get the new drug on the market. A drug cannot be sold at all unless it has been approved by the FDA for at least one indication. Once a drug is approved (and again, that approval is tied to a specific disease indication) it can be sold on the market. The drug company, however, can only market the drug for the approved indication, and only to doctors in a relevant specialty. They can also now advertise the drug directly to the public.

Any use of the drug for something other than its precise indication is considered “off label.” The FDA does not regulate medical practice, however, only drug companies, so doctors can use approved drug in any way they feel is appropriate. (There are other regulatory mechanisms to maintain the standard of care in terms of what doctors do in practice.)

Drugs often have multiple and complex effects on the body. This means they always have some side effects, but it also means they can have multiple beneficial effects as well. Also, diseases may share features or mechanisms and therefore one drug may be effective for multiple conditions. Drug companies may seek approval for additional indications, but the only reason for them to do this is if they think it will expand the market for the drug. This is therefore a marketing decision, not a scientific one necessarily. Drug companies have tried to skirt the rules by promoting off-label use in he past, sometimes resulting in mutli-billion dollar fines from the FDA.

There are times, however, when there is solid published evidence supporting off-label use of a drug, and in fact such use of the drug may be life-saving or cost effective (in other words, good medicine). Some have argued that restricting drug company promotion of off-label but evidence based use of certain drugs harms consumers and public health.

I have taken the position that congress should explore new rules for the FDA that will allow them to approve off-label promotion of drugs based upon a review of existing published peer-reviewed research (therefore the drug company does not have to spend millions of dollars on new research just for the FDA). But (and here is the key, relevant to the new development) – there needs to be an official review of the evidence to determine which claims are sufficiently evidence based.

The basic concept here is that it is the FDA’s role to protect the public not only from unsafe drugs and health products, but also from false or misleading corporate claims or advertising.  (The Federal Trade Commission also shares this latter responsibility, although the FTC is restricted to post-market regulation.) How can they do this if not by reviewing claims?

Now we get to the crux of the recent court decision. This was an appeals court decision resulting from a case brought against a drug company sales representative who was promoting off label use of the company’s drug. He argued that doing so was protected free speech. He was simply relaying the results of scientific research, and the FDA does not have the right to essentially muzzle him from discussion public information. Further, off label use of drugs is not illegal, so he was not promoting any illegal activity.

Two of the three judges in the case decided that the FDA did not have the power to restrict free speech that was essentially promoting an evidence-based and legal activity. The one dissenting judge, however, pointed out that this will create a precedent that will effectively neuter the FDA in terms of regulating drugs sales. I would add that this precedent will extend beyond drugs to supplements and any health care product or service, and will not only neuter the FDA but the FTC as well. (Orac wrote about this topic yesterday and made the same point. )

I tend to agree with the dissenting opinion in this case. Freedom of speech does not give people carte blanche to make whatever commercial speech they desire. Looked at another way – I am a big believer in the free market, but markets are constructs and they are constructed of rules and regulations. In the marketplace of medicine, unrestricted claims and marketing, in my opinion, lead to chaos. The consumer will be overwhelmed by complex claims that are very difficult to assess because they involve understanding the scientific literature in a thorough and nuanced way. There needs to be at least a basic filter in place to weed out patently false claims and give a minimal reassurance that health claims are reasonable – and then let the public decide among legitimate claims. In an unregulated marketplace, however, legitimate claims will be overwhelmed by slick but false or misleading claims. I give as evidence for this the supplement industry.

There is a balance between freedom and open markets, and also regulations to assure at least a basic level of honesty, fairness, and safety. Just citing freedom of speech on one side of the equation ignores this balance.

I don’t necessarily think we are currently at the optimum balance. We are too far to the freedom end with some things, and the regulation end with others. I do think, as I stated above, that it would be reasonable to have more efficient and less expensive review processes to approve the marketing of off-label use of drugs, and for specific health claims for supplements – as long as there is some review process. Otherwise it is left to the FTC to clean up the mess after the fact, and they are already overwhelmed.

Hopefully this decision will spur meaningful discussion on this issue. Let’s not get bogged down in accusations of evil government regulators or evil big pharma. There is a rational compromise in the middle.


23 responses so far

23 thoughts on “Promoting Off-Label Use of Drugs”

  1. nybgrus says:

    I agree with you fully Dr. Novella.

    Free speech has a precedent for being limited in cases of direct and obvious harm – yelling “Fire!” in a crowded movie theatre is the classic example. The question is how do we deal with more nuanced ways of free speech causing harm? I think it is fair to say that we can’t limit free speech based on someone being offended at the speech. However, verbal abuse can be genuinely abusive and harmful. But then we have laws to protect against that, because it would become criminal harrassment or assault. In this case we find no legal protection against representatives of drug companies making completely spurious off-label recommendations and thus leading – directly, though in difficult to detect ways – harm to the public.

    We have already seen how drug companies are absolutely willing to push every limit and loophole of the law in their development and marketing of drugs. Having this precedent allows cart blanche to do as they will. I have no doubt that representatives will be considered expendable and since many of them work for a bonus, there is significant financial incentive to really push this to the limits which will undoubtedly be deleterious for public health.

    At my institution drug reps are not allowed anywhere on any of our campuses. Off campus drug rep funded “journal clubs” still happen from time to time, but they are strictly limited to being off campus, on the participants own time, and no more often than quarterly. I also think it is ridiculous for prescription drugs to be marketed to the public on television. As far as I know, we are the only developed (and maybe only period) nation to allow this. Obviously there is a financial upside for the drug companies, but I see no scientific upside (if anybody has an angle I haven’t thought of I am genuinely interested to hear it).

    In any event, I think creating a blanket protection of what is undoubedtly commercially motivated speech in a field known for taking advantage of legal loopholes is a bad idea.

  2. Direct to consumer (DTC) ads are complex. They can have positive effects (see

    They can potentially increase awareness of a beneficial treatment, give consumers information to ask their doctor about, and get them more engaged with their treatment decision-making.

    I don’t think the final word is in yet about the net effect of DTC drug ads, but I would not assume it’s a net negative or just about drug company profits.

  3. steve12 says:

    “Free speech has a precedent for being limited in cases of direct and obvious harm – yelling “Fire!” in a crowded movie theatre is the classic example.”

    The only reason that one won’t go down is because it doesn’t benefit some wealthy demo. Otherwise, we’d have to watch it fall to this new Freedom Fetish in the US. It’s what’s ushered in Wall St shenanigans (repealing of Glass Steagall et al.), absurdly low tax rates on investments, unlimited & untraceable campaign contributions, and lack of action on climate change.

    What I’ve noticed is that these sacred freedoms can only be exercised by a tiny, tiny minority of people, and are in no way applicable to the rest of us.

    I wonder why that is?

  4. nybgrus says:

    Thanks for the link Dr. Novella.

    I suppose I can see the benefits of having the population more engaged with their care and asking questions. I suppose it is my anecdotal bias that keeps creeping in though, because more often than not – in my experience – it turns into patients demanding specific drugs when they aren’t indicated or when there are better options from a financial perspective. The FDA survey results seem to contradict this notion of mine. How reliable they are and if it really is 88% of people that would be contrary to my assumption, I cannot say. I would even toss in the question about the objectivity of physicians since we know that exposure to sales reps influences prescription practices, so perhaps some of this concordance is an overlap of bias. But in any event I have to concede that at least some large portion of people are in that camp.

    I am still unconvinced that the net good outweighs the net harms, particularly given that supplement ads tend to copy DTC pharmaceutical ads in style thus further garnering false legitimacy and conflating the two sorts of claims. But I will have to be a little less strident in my thoughts.

    Interestingly and related to your original post, is this section from the FDA link:

    That means the agency must ensure that prescription drug information provided by drug firms is truthful, balanced, and accurately communicated. This is accomplished through a comprehensive surveillance, enforcement, and education program, and by fostering better communication of labeling and promotional information to both health professionals and consumers.

    It seems obvious that a DTC ad from a pharmaceutical company should be supported by evidence and be balanced and accurate. I see this protection of off-label use recommendations by pharma reps as being a very easy way to completely mitigate that goal. Being allowed to promote off label would mean encouragement to promote off label and anyone can claim that a rep making a strong (but appropriately vague) statement that “others are using it off label for [X] condition” and chucking in a bit of basic science fact would meet the criteria of “truthful, balanced, and accurate.” As long as the rep doesn’t say you should use it for this off label condition or that it has been established that there is evidence for the off label use, then they are 100% legally protected. Even saying something as vague as “I’ve heard of physicians using [X] for [Y]” becomes an influential statement which may have little or no basis in reality or evidence, but would be equally protected. And that doesn’t even get into the possibilities of knowingly going beyond those bounds.

    It is indeed a complex and nuanced topic. I just tend to think that the nuance makes it extremely difficult and perhaps (practically) impossible to quantify accurately and tend to think erring on the side of caution is preferred.

  5. ConspicuousCarl says:

    steve12 on 07 Dec 2012 at 12:11 pm
    What I’ve noticed is that these sacred freedoms can only be exercised by a tiny, tiny minority of people, and are in no way applicable to the rest of us.

    It’s always ridiculous to see someone make some rant against the value of free speech while they are running their mouth on the Internet. Apparently, by your own brief description of “lack of action”, your opinion conflicts with what the government has decided. And yet nobody is silencing you over it! You must be one of that tiny minority.

    I must be too, since I bought stock and got paid dividends. Or maybe not. The corporation I bought stock in had up to 30% of their profits taken before the dividends were distributed, AND I had to pay tax on those dividends after that, so I must not be in whatever secret “absurdly low” tax club you are talking about.

  6. Xplodyncow says:

    As I’ve posted elsewhere, this ruling seems to be based on a false assumption, that preventing a rep from discussing off-label uses “prohibits the free flow of information.”

    Draft FDA guidance posted a year ago acknowledges that Big Pharma is sometimes the only source of off-label information. Reps can put a doctor in touch with their company’s medical information department–staffed with MDs, not salespeople–for the specific data.

    So it’s not like crucial information is being kept from physicians. It’s just that the reps, who aren’t extensively trained in off-label uses anyway, can’t say very much about it. How is that a bad thing?

  7. sonic says:

    While I agree with what Dr. N. suggests about how to deal with this situation and I agree that direct marketing has a variety of effects both good and bad–

    The FDA link provided by Dr. N. about the direct marketing discusses the results of a surveys done by the fda in 1999 and 2002.
    Here is a link to more specifics–
    (look down to Attachment C)

    The consumer surveys were done by phone.
    The doctors to be surveyed were randomly selected from a large data base of doctors (excellent!), but the doctors were given a choice to respond (ouch!) and the response rate was 46% (indicating a large degree of self-selection in the process of sampling).
    Some of the questions asked for subjective evaluations of things like “Do you feel pressure to prescribe…”, the type of question that is as good for determining bias as getting the real answers.
    And the type of question that might get different answers now- over 10 years and bazillion advertising dollars later– ya, know?

    I think these results need to be updated and the surveys done more thoroughly before taking them too seriously. I’m not sure that the last 10 years of saturating the ad market with drug ads hasn’t changed the dynamic (every magazine is filled with them and the TV has a drug ad every few minutes).

    Perhaps a vigilant attitude is the correct one here- after all, I’m guessing the drug companies will want advertising techniques that lead to people to ask for their products by name. Think that’s a good guess?

  8. nybgrus says:

    Very solid points, Sonic, and exactly the source of my skepticism as well. I think I had the appropriate amount and type of skepticism based on my lack of knowledge on the topic and my lack of time to review it in any depth.

    But yes, all of those certainly do cloud the picture and, IMO, make whatever positive effects purported much smaller. But I still must concede there are indeed some positive effects, though my overall stance remains the same.

  9. Jared Olsen says:

    Nybgrus: New Zealand (but NOT Australia) is the only other country in the world that allows DTC drug

  10. ccbowers says:

    This is a topic that I have a lot of thoughts about, but have a hard time coming up with solutions to the difficult trade-offs. I agree that a more streamlined process for adding indications (to already existing drugs) that is more flexible could be very helpful… not just for brand names (which really the only time Drug Rep issues come up), but for generic medications for which there is little/no incentive to get additional indications.

    Although I think the free speech issue is a legitimate consideration, I fear the consequences of easing up on the restriction on off label uses. There have been many situations in which a given drug was thought to have potential to treat a wide range of indications, was approved for one indication, but later failed to provide enough evidence for others.

    If a drug company knows that it could promote off label uses, then once the data was looking mixed for a given indication, they could decide that they would be financially better off if they did not pursue the additional indication (and additional research). They may be better off financially in a given situation to just promote the off label use with cherry-picked data, avoiding additional cost of research and possible failure at getting the indication approved.

    This will effectively carry some of the problems of the supplement industry into the prescription drug world, and that is not good at all

  11. BillyJoe7 says:

    In Australia, advertisements by pharmaceutical companies look like public service announcements. They publicise the disease but they are prohibited from mentioning their product. There is usually end with “ask your doctor” and a link to their website but at least there is no “in your face” advertising of the product name for patients to pester their GPs with.
    It seems to me a reasonable compromise.

  12. BillyJoe7 says:

    ^Sorry, edit fail

  13. Kawarthajon says:

    I have to disagree with your broad approval for off-label drug use. In my opinion, it is often abused when prescribing psychotropic drugs to adolescents and children, especially those children/teens who are difficult to manage and have severe behavioural disorders. Warnings about unproven, off-label use of drugs with children/teens are frequently ignored and they are overprescribed drugs that can be dangerous and sometimes kill them. I believe more regulation is needed when prescribing off-label drugs for children/teens.–adult-antidepressants-suspected-in-suicides-of-canadian-kids

  14. steve12 says:

    ConspicuousCarl said:

    “It’s always ridiculous to see someone make some rant against the value of free speech while they are running their mouth on the Internet. Apparently, by your own brief description of “lack of action”, your opinion conflicts with what the government has decided. And yet nobody is silencing you over it! You must be one of that tiny minority.”

    I wasn’t talking specifically about speech and never said that I was being silenced in any way. It’s always helpful to read what people have written, then say rude things about them running their mouth.

    My point was that bad public policy that benefits very few people has been put in place in the name off freedom, but it’s all bullshit. E.g., let’s look at your completely incorrect reading of what I said about climate change. Climate change is not being dealt with, in large part, because the necessary policies would infringe on our freedom, which is absurd.

    The Wall St collapse was in large part caused by a lack of regulations, of course in the name of freedom. Capital requirements or reinstating Glass would be tyranny! Instead, we’ll just crash the global economy – but we’re free to do so!

    But none of these things are really about freedom for 99% of people – they’re druthers that are completely non-applicable to the average person. Yet the exercising of these freedoms for the few by the few costs us all dearly.

  15. nybgrus says:


    Nobody here is arguing for a broad or blanket acceptance of just any off-label usage. We are arguing that evidence based off-label usage is an important facet of quality patient care.

    Of course that requires some extra work and intellectual honesty on the part of the prescriber, as well as some sort of evidence base to work with (which, as we have seen thanks to Ben Goldacre is tougher than we had hoped). So of course there is opportunity for abuse as well as mistakes.

    But citing evidence of abuse of off-label use does not negate the fundamental principle and rationale for it. And citing evidence of mistakes being made doesn’t either. We fully recognize it is an imperfect system and no physician around these parts would like anything more than a robust set of data for all drugs for all indications in all populations. But that is simply impossible to do.

    Perhaps off-label use in children, particularly with psychotropic agents, is something over-abused and much more likely to mistakes in usage. In fact, I think that is an entirely reasonable argument. The question is how much are the harms and do they outweigh the benefits? One needn’t elucidate the precise outcomes of specific drugs in pediatric populations to do a good study demonstrating that we should exercise more caution and decrease off-label usage in [children in general, psychotropics in children, etc] and thus change the culture of usage to reflect this until we have better data to fill in.

    But merely saying there should “be more regulation” of something that by definition can’t really be regulated (that’s why it is called “off-label” after all) without offering some ideas for an alternative is a non-starter.

    Perhaps something like what Dr. Novella proposed where the FDA (or pharma co’s) can aggregate lesser evidence to provide a framework to better rationally direct off-label use. Couple that with a general admonition that children are a special population for whom these ideas apply less and that may be a reasonable solution. But until we are much better at what we do, have much more resources to devote to it, and a population with priorities and desires in line with it, I don’t see a fundamental shift in how it is done to be reasonable. Because a lot of off-label use is beneficial and I posit that completely removing it without any other fundamental changes in how we do things would be a net detriment to peoples’ health and well being. I could be wrong, of course.

  16. locutusbrg says:

    Usually you and I are on the same page. Not in this statement. “Direct to consumer (DTC) ads are complex. They can have positive effects”.
    I would disagree that. DTC marketing, especially television marketing, is frankly a waste of time and resources.
    Costly problem #1. Watch the national news and you will see ad after ad for prime time commercials. We are all paying for that. “In 2004, Astra-Zeneca spent $216 million promoting Crestor, almost matching the $212 million spent on Pepsi for that year.”

    “Pharmaceutical companies spend nearly twice as much on marketing in the U.S. as they do on research and development (R&D)”
    Gagnon, M. A. and Lexchin, J. (2008, Jan) The Cost of Pushing Pills: A New Estimate of Pharmaceutical Promotion Expenditures in the United States. PloS Medicine.

    Is this a judicious use of resources?

    Problem 2: Some would argue that you spend as much time arguing over the facts as beginning the conversation. Destroying any benefit of them being exposed to the new treatment.

    Problem 3: It is marketing not education. The greatest resources are behind new drugs. Biggest unknowns, risks, and expense. Good upside for company not patients. There is no drive to market proven treatments with a less favorable bottom line. Everyone knows what the “purple pill” is due to great marketing but how many people still are on it now?

    Problem 4: You and I spend a lot of time money and education to stay current in medicine. Is it realistic that a consumer can learn anything useful in a 60 second TV spot other than the tag line.

    I do not think that you can justify the money the US has spent on pharm in the last decade without considering the cost of marketing. I can think of several ways to better educate my patients about new treatment options other than antonio banderas voiced bee marketing. Or the 2007 zoloft commercial that asked the question have you ever had a bad day, or felt down.

    You can easily argue that it begins the discussion with you doctor or starts the patient looking for treatment. I give you that, but is it cost effective?
    In my opinion no.

  17. Kawarthajon says:

    “But merely saying there should “be more regulation” of something that by definition can’t really be regulated (that’s why it is called “off-label” after all) without offering some ideas for an alternative is a non-starter.”

    I have to disagree with you. It would be quite easy to regulate the off-label drug use – it is ‘off label”, not black market, illegal or clandestine. Regulation is a very complicated matter and there are many ways that the use of these drugs with children/teens can be controlled or even restricted. In my experience, general family physicians, who have no specialization in psychiatry or paediatrics, should not be prescribing psychotropic medication for children without knowing the efficacy of the drugs or the risks (which they often do). At the very least, these drugs should be prescribed only by a paediatrician or a child psychiatrist, someone with some specialized knowledge in the field. There should also be proper follow up with those specialists – what often happens is that a child will see a psychiatrist, who will write a script, but then ask the family physician to follow up with the patient. Again, that family physician does not have the expertise to understand how the drug may impact the child. Furthermore, it is common that group homes, youth jails and other facilities use these drugs in an effort to control children’s behaviours, when there are other means of controlling their behaviours that are more effective and less risky. Currently, there are few, if any, guidelines regarding off label use of these medicines for children. In my opinion, medical colleges and other regulatory bodies need to come up with standards of practice when prescribing medicines for children.

    “The question is how much are the harms and do they outweigh the benefits? ”

    If there is evidence to suggest that the medication is effective and has few risks, fine, prescribe the medication. The reality is, we either don’t know or we know they aren’t effective, but they are used anyway by people who don’t know what they’re doing. These drugs often aren’t tested on children or adolescents and, therefore, practitioners just assume that the drugs will do the same thing for kids/teens that they do for adults. Alternatively, they are tested but the results are buried by pharmaceutical companies (look up Study 329 for an example). Steve advocates for science based medicine. Off label use of a drug in this situation is not science based. There is some evidence to suggest that it can be harmful and, in some cases, contribute to the death of a kid/teen. We don’t know what impact these drugs may have on a child’s brain development, even though they are routinely used. We know more about the effect illegal drugs (i.e. marijuana) and alcohol have on child cognitive development, than we do about these commonly prescribed drugs.

    This is an excerpt from the article I linked to above:

    ‘Australian child psychiatrist Jon Jureidini, who has extensively researched Paxil’s safety and effectiveness in youth, said, “none of the antidepressant trials in children show any clinical advantage of the drug over a placebo. The ones that claim to have (shown such an advantage) have all got flaws in them, either scientific or in the way that they’re presented. That means we have no evidence at all to support the use of antidepressants in children.”’

    “Because a lot of off-label use is beneficial and I posit that completely removing it without any other fundamental changes in how we do things would be a net detriment to peoples’ health and well being. ”

    I never advocated for removing off-label drug use. Steve was talking about areas in which it can be helpful – where there is evidence that it is helpful. My wife was prescribed domperidone (a drug banned in the US by the FDA) – it is a stomach medication that prevents nausea – but they accidentally found out that it increases breast milk production (an off-label use), which is why my wife took it. I just think that off label use is reckless in the case of children receiving psychotropic medication, especially when we know that certain drugs have no efficacy with young people.

  18. SimonW says:

    The freedom of speech issue is a red herring, he can quit being a drug rep in one phone call to his boss.

    When he is a drug rep, he is paid to tell doctors the approved uses of the drugs he is selling, not his opinion or what the company would like him to be able to say.

    If the drug companies are prepared to accept liability for off-label uses promoted by their representatives, rather than doctors, I’m sure we can come to a compromise, until then I suspect a mistake was made here and it will likely be successfully appealed.

    I agree it may be a difficult position for a drug rep, but it is probably more helpful if the law is clear (no promotion of off-label uses) than some more nuanced position.

    Vioxx was promoted off-label with Merck both ignoring FDA warnings, and withholding safety data. The story of Vioxx is shady from beginning to end, and highlights why such restrictions are a necessary safeguard and thus justify a restriction on the free speech of drug salesmen.

  19. locutusbrg says:

    @ Kawarthajon
    “Australian child psychiatrist Jon Jureidini, who has extensively researched Paxil’s safety and effectiveness in youth, said, “none of the antidepressant trials in children show any clinical advantage of the drug over a placebo. The ones that claim to have (shown such an advantage) have all got flaws in them, either scientific or in the way that they’re presented. That means we have no evidence at all to support the use of antidepressants in children.””
    ” I just think that off label use is reckless in the case of children receiving psychotropic medication, especially when we know that certain drugs have no efficacy with young people.”

    To admit I have the same reservations, but I would like to point out you have to answer several other questions before you can make that blanket statement. reckless and no efficacy.

    1. Does what he says about the research match with the research on paxil? otherwise it is just an argument from authority.
    2. Is there good research in other drugs of that class in children?
    3. What does that research say about safety and efficacy?
    4. How long has the class of drug been used in children and what is FDA( or aussie eqiv.) feedback?

    If all those pieces line up with an equal fail I think your point is valid. If it just opinion and scare mongering with children as a emotional component then no.

  20. Kawarthajon says:


    In my opinion, I am not fear mongering. I believe that medicine should be prescribed if there is evidence that it is helpful (i.e. stimulants for AD/HD in children), as long as the proper follow up medical care is provided to ensure that the side effects aren’t more harmful than the problem they are trying to resolve (i.e. liver damage, weight gain, no effect on behaviours, etc.).

    There is no research to suggest that Paxil is helpful for children. There has been research on the subject, by GSK. It is not an “argument from authority” because the guy I quoted above has actually done research on Paxil for children and found that there is no evidence to support its use. There has also been a successful lawsuit against GSK by the US Dept. of Justice for falsely promoting Paxil use in children. The company was fined $3 billion for, in part, promoting Paxil use in children/teens. (

    Search for Study 329 for more information about the misinformation provided by GSK.

    Paxil is not safe for children, in my opinion, because it does not provide benefits (this has been researched) and there is evidence to suggest that it increases the risk of suicide in depressed teens and children (this has not been thoroughly researched, but antidepressants now carry warnings about this).

    The FDA has not approved Paxil for use with children/adolescents, neither has Health Canada or the UK equivalent. I don’t know about the equivalent agency in the Australian government (I’m not Australian).

  21. nybgrus says:


    But you still haven’t addressed how to do this. How can you regulate that? Make a law that says on pediatricians can prescribe drugs to children? Or limit it to classes of drugs in certain cases? How do you define that? And especially only for off-label use? It quickly becomes a quagmire to implement and navigate. Also, your experience aside, many family practice physicians actually take the time to gain further knowledge and relevant specialization. How do you regulate that? Is their knowledge suddenly worthless? Do they have to get official licensure? Who would devise it? On what evidence would it be based? Would the patients of this doctor suddenly need to go to a child psychiatrist? What if there wasn’t one available nearby? Or in the network of the patient? Or didn’t have an appointment for a very long time?

    It is vastly more complicated than just saying we should regulate an off-label use. Because yes, while it isn’t illegal, it is still off-label. So how do you then define the regulation you wish to impose? Because saying “Any use not on the label” is too broad – it (potentially) affects to many populations with too diverse a range of conditions. So then you have to be specific, and that becomes the quagmire.

    Your further assume that the family physician doesn’t have the necessary or relevant expertise. This is certainly not true. Family/general practice physicians are specifically trained to be within their limitations. They will hedge and say a referall is needed to prescribe medications they are not comfortable with (and since your evidence is experience, I will counter with mine – in my GP rotations, I had many instances with new patients and child patients asking for psychotropic medications and the attending GP refused to prescribe more than a handful to get them by until proper follow up was met with the referall we gave). And it is also false to think that a GP can’t then follow the case – part of the training is to recognize when things go wrong and a referall back to specialist is needed. Insisting that all cases must be initiated and followed by a specialist (in this case sub-specialist) is onerous, expensive, and certainly not necessary. Certain more difficult and complicated cases do, and those are, usually at the bhest of the GP.

    The issues raised here are more about bad doctoring rather than bad regulation and a need for a plethora of laws to describe every scenario for every off label use of every drug. And it is sadly tough to regulate bad doctoring. I would also argue that it is the minority – though still a significant problem – that would fall under this category.

    There are few regulations regarding off label use… for exactly the reasons I have been discussing. As I said before, creating a system to make an evidence base to help guide off label use is, IMO, a decent idea. But I still fail to see how to regulate things the way you seem to think they can/should. Perhaps I am misreading you, but at least a good chunk of what you have written is based on incorrect assumptions and experience rather than actual data – which contradicts what I know about how physicians are trained and how we are already supposed to act.

    Furthermore, in regards to your link about the child psychiatrist, there are studies which claim there is no efficacy beyond placebo for any anti-depressants in any population… which have been thoroughly debunked by the likes of Jim Coyne and others. The point is that accurate measurements and quality studies are hard to do, and much more so in special populations like children. It is absolutely unfair and untrue to say that they do not help any children at all and that most prescribers don’t know what they are doing. They do help, and in many cases it is a limit of knowledge on the topic rather than a limit of practitioner knowledge that is the issue. So you are left either throwing the baby out with the bathwater or merely saying “Exercise more caution when prescribing to children” which is something already drilled into our heads and not something one can codify into a regulation.

    I am certain more clever people can come up with a few god regulations to improve the situation, but it is not as simple as “regulate it more and make it so that only pediatric psychiatrists can prescribe…”

  22. daedalus2u says:

    I think the FDA should ask for comments on changing the policy on off label use and see what Big Pharma wants.

    The FDA can allow free speech on off-label uses, but restrict MD prescribing power to only on-label indications, or they can keep the status quo which is prohibiting off-label marketing by drug reps but allowing off-label prescribing.

    Maybe the FDA can’t regulate drug rep speech, but the FDA can regulate MD prescribing authority.

  23. locutusbrg says:

    One person’s opinion about their own research can be argument from authority especially if it contradictory to the majority of science related to that topic. SSRI as a class have a great deal of research associated with them. If you cherry pick paxil as one drug of that class and say no efficacy in pediatrics you are ignoring the body of research associated with it. I agree that the body of research is weak in SSRI in children. I am not advocating that SSRI be widely prescribed for children. The type of dismissive absolutism you advocated based on a single physician’s opinion smacks of dogma not science. Again medicine research is more complex than one study or focusing on one drug’s body of research. You require multiple lines of evidence from the entire class of medications.
    I am against any legislation about medication that takes decision out of the Physician and Patients hands, and places limits on treatment option. It would be onerous and impossible to utilize the resources to research every drug in every scenario that a drug may be prescribed. Laws are inflexible and do not allow for quick reaction. There are reasonable conclusions a physician can make based on the body of research related to the drugs about safety and efficacy. It is not perfect but it very good.

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