For all that Americans spend on prescription drugs — $425 billion last year — you’d think we’d actually take our medicine.

But one of the frustrating truths about American health care is that half or more of prescribed medication is never taken.

It’s called medication nonadherence, and it’s a well-documented and longstanding problem, particularly for patients with chronic conditions. The drugs they’re prescribed are intended to prevent costly complications, reduce hospitalization, even keep them alive. But even when the stakes are high, many patients don’t take their meds.

This seems like a problem we ought to be able to solve. It motivates high tech approaches, like digital pills that can automatically communicate to doctors that they’ve been taken.

Maybe people forget to take their meds — about 60 percent of people say as much — so we just need to remind them. Maybe people don’t understand the value of what they’re prescribed, so we just need to educate them. Maybe drug regimens are too complex, so we just need to simplify dosing.

All these methods have been tried. It’s not so clear any of them work very well.

Only one approach has repeatedly been shown to be effective: reducing the cost of medications.

First, let’s look at the research on the other methods. So-called reminder packaging — pill packaging or containers that organize drugs by single dose or day of the week — is a relatively simple idea intended to help people remember to take their prescribed dose.

A systematic review by the Cochrane Collaboration found that it was helpful in doing so, but only modestly. Surveying 12 randomized controlled trials, the authors concluded that reminder packaging increased the number of pills taken by patients by 11 percentage points. But they also found that most of the studies had significant methodological flaws, casting doubt on the findings. Other systematic reviews of reminder packaging studies also found problems with the research, like small sample sizes and short follow-up periods.

Perhaps reminder packaging is too passive, and patients need something like an alarm to alert them when they’ve missed a dose. Electronic pill monitors can do that. Some just remind patients to take their medication. More sophisticated ones alert doctors when they don’t. In 2014, a team of researchers from the Brigham and Women’s Hospital and Harvard Medical School published a systematic review of such devices in the Journal of the American Medical Association. Here, too, the results are disappointing. Most studies of such devices do not detect improvement in adherence.

A recent randomized trial not included in these systematic reviews tested three dose reminder approaches for people with a chronic health condition or depression: a pill bottle with toggles for each day of the week that can be changed after each daily dose; a pill bottle cap with a digital timer displaying the time elapsed since the medication was last taken; and a pill organizer with a compartment for every day of the week. Over 50,000 subjects were assigned randomly to one of these approaches or to none, as a control.

None of the devices performed better than the control in getting patients to take their medications. One possible explanation is that forgetfulness may not be why patients don’t take their medications as prescribed. Drug costs, a wish to avoid side effects, and a desire to be less reliant on drugs are some of the other reasons patients don’t take them.

“It is also possible that for reminder devices to be effective, they need to be coupled with other adherence-improvement strategies,” said Niteesh Choudhry, lead author of the study and a physician with Brigham and Women’s Hospital and Harvard Medical School.

That’s why augmenting electronic monitoring with other information or assistance delivered to patients may be more successful, if more expensive. For example, one study found that the adherence of hypertensive patients increased when digital display containers were combined with a blood pressure cuff and a card for recording blood pressure. This suggests that when patients receive feedback that signals how well they are controlling their condition, they may be more willing to take their medication.

Still, it isn’t hard to find studies that show that even with considerable support, getting patients to take medications can be challenging. A Cochrane review examined randomized controlled trials of interventions — across many dimensions — to increase medication adherence. Reminder packaging and alarms were just some of the methods assessed, with approaches including patient and family education about the value of medication, and mail or telephone follow-up.

Of the 182 randomized trials reviewed, four stood out as the most methodologically sound. Among those, two increased adherence but two did not. Over all, the authors concluded that there was a lack of convincing evidence that even complex and costly interventions significantly increased patients’ compliance with drug regimens.

“A cure for nonadherence is nowhere to be seen,” they wrote. A more recent study not included in the Cochrane review found that not even providing patients with financial incentives and social support, along with pill bottles that signal when a dose should be taken, was enough to boost adherence among heart attack survivors.

So why is price so important?

When drugs cost them less, patients are more likely to fill prescriptions. Even if people have already purchased drugs, they may skip doses — or split the pills — because of concerns that they won’t be able to afford future refills. Free drugs don’t get everyone to take them, but many more do so than if they have to pay for them.

For those with certain chronic conditions, extra help in affording medications can reduce adverse events and hospitalizations — a big increase in quality of life, as well as a potential benefit to the wider health care system and the economy.

Lowering prescription drug costs has been a longstanding pursuit for many politicians, and Medicare Part D and the Affordable Care Act helped (although most Americans still say costs are too high). President Trump said drug companies “have been getting away with murder,” but lower drug costs have not yet been a top priority of this White House.

if prescribers and Pharmacists are held AT FAULT.. when a person takes more medication – particularly controlled medications – than is prescribed… why are those healthcare professionals NOT HELD AT FAULT.. if pts fails to get their prescriptions filled and/or don’t take the medication as prescribed… both scenarios is basically medication nonadherence.

Could it be that the DEA has “over sight” of the first and no one has the authority,  the funding, or gives a crap about the latter ?