14 Meds Widely Used Off Label Need More Study
7 CommentsBy Ed Silverman // November 24th, 2008 // 1:55 pm
A group of researchers has assembled a list of 14 widely prescribed meds that urgently need additional study to determine their safety and effectiveness for off-label usage. As it so happens, antidepressants and antipsychotics are the most prominent types of drugs on the list, which specifically targets meds that are widely used off-label without proper scientific backing.
At the top was AstraZeneca’s Seroquel, which yielded the highest off-label rate with limited evidence (76 percent of all uses). The pill also had features that raised additional concerns, including its high cost at $207 per prescription, heavy marketing and the presence of a “black-box” warning from the FDA, according to Randall Stafford, associate professor of medicine at the Stanford Prevention Research Center, who is the senior author of the study, in a statement.
The most common off-label use for six of the 14 drugs on the list was for bipolar disorder. Another antipsychotic ranking high on the list is Johnson & Johnson’s Risperdal. The study appears in Pharmacotherapy (here is the abstract).
“Many of the drugs and the conditions on the list represent situations where inadequate response to treatment is common and where drug side-effects are frequent,” Stafford says in his statement. “Not only are these areas where patients and physicians are naturally interested in trying off-label therapies, but areas targeted for expansion by the makers of these drugs. When the volume of off-label use of any drug reaches the magnitude that we’re documenting, it suggests a role of the pharmaceutical industry in facilitating these types of uses,” he added.
To compile the list, the researchers convened a panel of nine experts from the FDA, health insurers, pharma and academia, and identified three factors: The volume of off-label use with inadequate evidence supporting the use (based on an ongoing national survey of physician prescribing patterns conducted by IMS Health); drug safety based on any warnings issued by the FDA; and a composite of the drug’s cost, how long it had been on the market and the amount spent marketing the drug.
Stafford collaborated on the research with lead author Surrey Walton, assistant professor of pharmacy administration at the University of Illinois-Chicago, and other researchers at UIC and the University of Chicago. The study was funded by the US Agency for Healthcare Research and Quality.
Salmon
This is quite interesting:
It’s not only drug companies and opinion leaders who have been pushing antipsychotics for off-label use in bipolar disorder, NIMH has been too.
On May 7th, 2007 NIMH issued a press release where they talk extensively about Kathleen Merikangas, Ph.D. and her work on bipolar disorder.
The title of the Press release was “Bipolar Disorder May Be Underrecognized and Improperly Treated”.
They claimed that Bipolar I (BP-I; full blown mania) and Bipolar II (BP-II; Hypomania) each effects 1% of the population and Bipolar Not Otherwise Specified (BP-NOS) effected 2.4% of the population. Now BP-NOS is essentially depression with activating features, i.e. hostility, irritability, psychomotor agitation, (ants in the pants). The article said that 97% of people who had some type of bipolar disorder (including BP-NOS) had a comorbid disorder, e.g. anxiety, depression, ADHD and weren’t receiving appropriate treatment and people with BP-NOS were typically treated by general practitioners.
(This past year there was also an announcement that NIH said that 2.4% of people diagnosed with recurrent unipolar depression really had BP-NOS.)
The article states:
“The researchers found that many were receiving medication treatement considered “inappropriate” for bipolar disorder, e.g., they were taking an antidepressant, or other psychotropic medication in the absence of a mood stabilizing medication such as lithium, valproate, or carbamazepine. Only about 40 percent were receiving appropriate medication, considered a mood stabilizer, anticonvulsant or antipsychotic medication.”
The 40% appears to be the patients with BP-I and BP-II, yet if you look at labeling for the the antipsychotics they’re not even approved for BP-II (hypomania). They’re possibly like antidepressants where only the sickest patients respond. It they do work for BP-II then why wouldn’t the drug companies actually study them in Hypomania and get the indication. Maybe it’s because when you look at the data from published studies the antipsychotics only bring patients down to the level of hypomania and therefore don’t expect them to work. If that’s the case then using some of these drugs in BP-II and BP-NOS is clearly not justified.
Besides how can we even be sure someone has BP-NOS especially in children where the proposed symptoms are kids who have ADHD who may not fully respond or who have a tantrum that lasts more than a few minutes.
There’s already probably a lot of kids who are inappropriately diagnosed with ADHD, so now we’re going to add another disease that’s even more difficult to diagnose and we’re going to give criteria to pediatricians and propose they take care of it. Looks like a big mess to me and a lot of profits to the drug companies.
Oh by the way did anyone notice how Lilly, (Glaxo?) and Harvard are on the NIH science board advising NIH where to do research.
Salmon
Neil Manowitz, PhD,
Excellent comment, Salmon. You’re correct in that I failed earlier to acknlowledge that KOL’s exist at NIMH as well. Your comments support the idea that their entanglements with pharma can be just as murky as those at the universities.
Former SP
Why should drug companies do more study when they can promote off-label and hope they don’t get caught. If they do, they pay a fine, admit no wrongdoing, and laugh all the way to the bank. It’s a great gig if you can get away with it!
pharmavet
Has anyone noticed that nine of the fourteen drugs on this list are psychotropics?
Meg
Fourteen drugs on this list are psychotropics..Let’s hope that the incoming Administration is not for sale to Pharma as the outgoing one has been ever since 2000. Bush, if he is not indicted and jailed for his numerous crimes, can still hang out with Syd Taurel (unless he is indicted for death and destruction due to Zyprexa), as Lilly execs have been friends with the Bushes for three generations.
If Obama can “get it”, the FDA will, as Ed posted from the Wash. Post, have to be rebuilt from the ground up. This will not be easy as the pharma lobbiests will swarm like bees. But if changes are not made, our society will continue to tolerate 100,000 dead from prescription drugs each year, children marked for life from drugs and labels, and untold grieving families who have yet to see any justice.
I liked the earlier descriptions of the culture of pharma. Who with a conscience could bear to work there. As for people like Biederman, I must say that the vast majority of psychiatrists I’ve seen or my children have seen have some sort of personality disorder, including a lack of any empathy. I guess that must be the type of person who picks the specialty. Not true with psychologists.
PhD, FDA Reviewer
“Who with a conscience could bear to work there.”
You have to ask yourself which is worse, putting up with the threats, intimidation, and harassment, or living with yourself later knowing you were keeping things from being even worse and instead now are just letting them happen.
If the staff reviewers don’t make a stand, who else is going to do it?
The opinions are my own and do not reflect the opinions of the FDA
Justice in MI
“If the staff reviewers don’t make a stand, who else is going to do it?
The opinions are my own and do not reflect the opinions of the FDA”
I understand that the opinions are your own, FDA Rev. But they are shared by many others - as you know, that includes people at FDA and a great number of people who are not. Thank you for your service and courage.