About seventy-five percent of the time, there’s a complete lack of clinical evidence supporting the efficacy or safety of the off-label application.
I’ve railed before about the widespread problem of off-label prescribing, where doctors order a medication for a purpose other than that originally approved by the FDA. For instance, a common off-label application occurs when a patient complains of insomnia and the doctor prescribes antidepressants, although the FDA has approved antidepressants only for cases of depression — not for insomnia. As I wrote in that blog entry, off-label prescriptions account for at least 21 percent of pharmaceutical sales, amounting to at least 150 million prescriptions annually. And in fact, once a drug has been approved for any condition, physicians can prescribe it for any other application they choose without repercussions. About seventy-five percent of the time, there’s a complete lack of clinical evidence supporting the efficacy or safety of the off-label application.
The New England Journal of Medicine, “The FDA may be conceding to drug manufacturers the responsibility for regulating their own off-label marketing practices. … I believe that the FDA must take an active role in fostering evidence-based practice, eliminating subversion of the approval process, and requiring a balanced and fair presentation of the scientific evidence.”
Recently, some news came along supporting my (and Dr. Stafford’s) contention that the FDA’s lenient stance toward off-label prescribing requires a closer look. It seems that some in the medical community became concerned after the FDA proposed legislation last February that would have made it even easier for drug companies to market their products for unapproved use. Working with Dr. Stafford, scientists from Stanford and the University of Illinois compiled a report listing 14 drugs commonly prescribed for off-label use where there is little or no evidence that the drug works for the unapproved purpose, or even that it is safe.
According to Dr. Stafford, the lead author of the report, “Off-label prescribing means that we’re venturing into uncharted territory where we lack the usual level of evidence presented to the FDA that tells us these drugs are safe and effective. This list of priority drugs might be a start for confronting the problem of off-label use with limited evidence.” Dr. Stafford suggests that the FDA should start regulating off-label use more stringently, starting with the 14 drugs on this list.
Most of the drugs named involve safety concerns and are inordinately expensive. For instance, one medication, Seroquel, approved for treatment of schizophrenia and manic-depression, has become popular as an off-label treatment for anxiety and depression, though it hasn’t been tested at all for these uses. The problem here is that Seroquel costs about $200 per prescription, and it’s a dangerous drug that bears the highest-risk “black box warning” from the FDA. Seroquel has been tied to an increased risk of death in dementia patients. Of the other 13 medications named, nine were anti-psychotics or antidepressants, and all replete with side effects.
Why so much off-label prescribing of mental health meds? Perhaps it’s because doctors get frustrated that patients don’t respond to their initial prescriptions, so they just keep trying with any available drug — desperate to help desperate patients. Or perhaps physicians assume that if a medication helps with one type of craziness or distress, it’s bound to help with another. It’s like assuming that if a drug heals one body part — say the stomach — it should help with the liver, too, since both organs fall somewhere near the midsection. In fact, the inference might have merit, but since it hasn’t been tested, the patient becomes a vulnerable guinea pig.
Then again, there’s the much-abused issue of anecdotal evidence (at least when applied to complementary and alternative medicine). For example, a physician uses Serequel for schizophrenia and the patient reports that he feels less depressed. The physician relays this information to his fellow doctors, and suddenly every doctor in the hospital is prescribing Seroquel for depression — and then these doctors tell their buddies at a conference. The next thing you know, doctors all over the country believe that Serequel works amazingly well for depression — sort of a dangerous adult version of the telephone game. And add to that the fact that pharmaceutical companies often pay physicians to prescribe their products for off-label applications — patient safety be damned.
And that’s a principal concern expressed by the research team — that patients take drugs as prescribed without realizing that the pill they’re popping hasn’t been fully tested or approved for their presenting condition. The concern becomes particularly pointed in view of the fact that much off-label prescribing involves kids. In fact, between half and three-quarters of all medications prescribed for children have not been approved for pediatric use. (Consider that the next time your doctor prescribes medication for your child.) That’s because the approval process costs a lot of money, and once the adult trials finish, the pharmaceutical companies don’t want to pay for retesting on younger subjects. They just scale down the dose for kids and “assume” it will work just fine, leaving a big question mark about long-term risks for young consumers and ignoring how side effects impact children as opposed to adults.
Most doctors contend that off-label prescribing sometimes saves lives and so shouldn’t be prohibited, which brings me to the point that so rankles alternative health practitioners. Doctors can prescribe drugs based on purely anecdotal evidence or even on the basis of the barest of rumors or even wishful thinking. In contrast, natural health practitioners are not allowed to prescribe comparatively benign herbs and nutraceuticals that have long and verifiable track records of safety and efficacy — often stretching back decades and involving millions of people. It hardly seems fair. Then again, fairness really has nothing to do with it, does it?