ROCHESTER — The list of reasons for the opioid epidemic is a long and tangled web. It includes rapacious profit-taking, aggressive marketing tactics, industry-financed continuing medical education, a subsidized pain lobby, lax oversight, brazen pill mills, cheap heroin, illicit fentanyl and the powerfully addictive properties of the drugs themselves.

Now we can add two more reasons to that list: the exhaustion of doctors when dinner approaches and their schedule has backed up, and, in something of a surprise, the apparent role of masculinity in prescribing opioids in cases where female providers would have chosen otherwise.

That's the finding of a pair of new studies, one examining gender differences in opioid prescribing, and the other on changes in opioid prescribing based on the time of day and degree of falling behind.

In the first of these papers, on the pre-print server MedRchiv, Stanford researchers reviewed the prescribing habits of 1.13 million medical providers who made drug claims on Medicare Part D in 2016. After electronically sorting the 1.4 billion claims for 40 million patients by physician gender and specialty, the authors reported "a consistent pattern of male providers prescribing more drugs per patient than female providers, with few exceptions by specialty."

When it came to opioids, the study added, males prescribed significantly more pills per patient than females in 22 out of 30 medical specialties, with male anesthesiologists, physician assistants and medical students among the specialties in which orders for opioids fell the most out of line with those of their female counterparts. Strangely, this male-centric phenomenon may be unique to American physicians. The authors noted a study in France found no gender differences among doctors in prescribing opioids.

In part because "shorter visits have been associated with increased prescribing," in the words of the Stanford team, researchers at Harvard and the University of Minnesota set about in a separate study to learn if tired and harried doctors tend to prescribe more painkillers.

"It's important to understand how physicians arrive at the decision to prescribe opioids," explains Hannah Neprash, a health economist at the University of Minnesota and lead author of a study published this week in the journal JAMA Network Open.

"There's this widespread belief that time pressure in medicine may change how doctors make decisions for patients. The common narrative you see is that prescribing an opioid for a patient experiencing pain is a quote-unquote 'quick fix' if the physician doesn't 'have the bandwidth or time' to discuss non-opioid options."

Naresh and a colleague looked at a database of over 600,000 primary care appointments for patients experiencing a new painful condition in 2017. Among the 5,603 physician prescribers studied, she found the likelihood of getting an opioid rose a third among these patients — from 4% to 5.3% — between the beginning of the day and the end of the day.

She also found the likelihood of getting painkillers rose 17% — from 4.4 % to 5.2 % — if a doctor was running behind schedule. Though these elevations in pill pushing may seem small, the changes translated into 4,459 extra opioid prescriptions written within the sample than if doctors had prescribed the same way after lunch as they did at the start of the day.

This rising willingness to prescribe pain pills as the day wore on did not translate to more liberal prescribing of non-addictive painkillers, or physical therapy, she adds, "which may be because those prescriptions don't really save doctors any time. They actually require more time for the physician to discuss with the patients why you might need to go through physical therapy to treat the pain they are experiencing. It might be easier to just say yes if they are running behind, or it's late in the day, or they are fatigued cognitively and physically.

"Part of the battle is knowing that this pattern exists," Neprash says. "Maybe it's using smart scheduling practices, where a clinic could try to identify the most difficult patients clinically, and put them at the beginning of the day. It could also come down to using a decision aide, or a shared decision making tool to make sure the physician and the patient have a conversation about the risks and benefits of whatever treatment their receiving."

Because hers was an observational study, Neprash cannot say conclusively if the opioid-prescribing doctors she studied were tired, rushed or frustrated. All that being said, she says, "all I know is that when I go to the grocery store at the end of the day, I make terrible decisions."