This review article dives into a problem that is well known to physicians, but perhaps not to many other groups. It’s an annoying (and worse than annoying) feature of medicine that decades of work have attempted to address: how do you get the patients to take the drugs?
It’s harder than it looks. Numbers are understandably difficult to come by, but every time people look into this issue in any detail, the answers come back pointing in the same direction. Estimates on non-adherence to treatment regimes are generally around 50% (!) for chronic illness in the US, for example, and it’s believed that poor adherence is one of the major reasons for the disparities in outcome that are seen between controlled clinical trials and real-world prescriptions. After all, in a clinical trial setting you often have someone standing right there watching each patient take the medication, at the right time and in the right amount (which is just one of the many, many reasons why such trials are so expensive. But “out in the wild”, people find all sorts of reasons to not get around to it.
Some of that is sheer forgetfulness and/or disorganization, two factors that should never be ignored in explaining human behavior. These are especially acute in older patients naturally, and these are the ones who are typically taking more medications. But there are others – patients may worry about side effects (ones they’ve already experienced or ones that they fear they might). The extreme example of this is vaccine avoidance, I’d say, as in some parents fearing that they might be putting their children at risk of autism or what have you. Thank you, Andrew Wakefield, for inflicting this on the world. In the real-side-effect world, treatment with agents like interferon can give people symptoms very reminiscent of the flu, which is not enjoyable at all. That tends to diminish over time, but some patients aren’t in the mood to wait it out. And of course, many people just do not like taking injections in general, and will find reasons to avoid it. There can be problems with some other routes of administration, too – the majority of patients, it seems, cannot properly self-administer eye drops.
Past that, patients might think that they aren’t getting any benefit out of the medication to start with, so why bother? This has always been a problem in treating hypertension, since you really can’t feel having reasonably high blood pressure, nor feel much of a difference when it’s lowered to better levels. Many CNS drugs (antidepressants, for example) have notoriously delayed onset (days, weeks), which makes it easy to assume that nothing’s working. The opposite of this occurs too, of course, if people start to feel better and then decide to stop taking the drug, which is a widespread problem with antibiotic prescriptions (although it also happens with asthma, relapsing multiple sclerosis, and other situations). And you can’t ignore the effect of drug costs, either, with some patients trying to stretch things out due to monetary worries or abandoning treatment altogether.
The paper linked in the first paragraph goes into a number of ways that have been tried over the years to get around these problems. Many of them fall into the extended-release category, where you basically take the repeated dosing decisions out of the patients’ hands. That can be very effective, but it’s tricky to get it to work pharmacokinetically. But the idea of a once-a-month (or once every six months) dose is very appealing if you can find a way to realize it. Some compound classes have this built-in, such as the bisphosphonates for preventing loss of bone density, but in other cases you have to design very slowly metabolized/excreted versions of an active compound, formulations that can be injected (say, intramuscularly) and break down slowly, or some kind of physical implant that releases the compound over time. This is a good spot to note, though, that adherence to bisphosphonate treatment is low, with some estimates that up to 75% of patients discontinue within the first year, through a mixture of not noticing any changes and worries about potential side effects. So extended-release alone will not solve every problem. The potential downside of extended release is immediate apparent, too: if a patient develops bad side effects from some drug dosed in this way, it’s not like they can just stop taking it. That problem has led to a number of schemes for ways to have some sort of “turnoff switch” built into long-term-dosing systems, be they small molecules or biologics.
But overall, anything that decreases the number of times a patient has to take a drug seems to improve adherence, so long as the new dosing schedule is seen as sensible. There’s plenty of evidence that once-a-day dosing is far better tolerated in the real world than any multiple-times-a-day regimen, for example, but a once-ever-other-day schedule would be tricky. Monday, Wednesday, Friday, Sunday, Tuesday, Thursday, Saturday. . .it’s easy to lose track. You’d probably be better off with once-a-week, but then the problem can arise of having dosing come up so infrequently that it’s easier to have it slip ones’ mind. A longer interval can allow for automatic reminders from a physician’s office, without these coming in so frequently as to turn into background noise and be ignored.
