New insights into the harms of taking medicines at the wrong time of day
Are you on any kind of daily medication? Do you take those drugs in the morning or the evening? According to an emerging body of research, the time of day you take a medication may influence how well it works, or how much it harms.
Tobias Eckle, from the University of Colorado School of Medicine, has been studying the relationship between circadian rhythms and drug efficacy for several years. Referred to as chronotherapy, this field of study looks to home in on how a human body responds to drugs at different times in our 24-hour circadian cycles.
Eckle said just four of the 50 most commonly used medicines in the United States have directions recommending they be taken at a specific time of the day. And there are two key reasons why doctors don't direct patients to take drugs at certain times.
"First, many physicians are not aware that some drugs work better during a specific time of the day," explained Eckle in an article for The Conversation. "And second, most drugs have not been studied for possible different effects during a 24-hour cycle. As such, patients are directed to take most drugs during the morning or evening primarily to ensure compliance."
Some studies over the past few years have started to point at certain specific relationships between drug efficacy and circadian cycles. A detailed 2019 study, for example, looked at how tumor growth can ebb and flow alongside circadian rhythms. The conclusion from that research was that certain breast cancer drugs should be administered in the morning to maximize efficacy.
Another compelling study investigated immune system activity and circadian cycles, wondering whether common non-steroidal anti-inflammatory drugs (NSAIDs) could negatively affect bone healing if taken at the wrong time. That research strikingly found that over-the-counter pain medicines may actually slow the rate of bone healing if taken late in the evening.
Eckle's latest study focused on a common pre-operative sedative called midazolam. Prior investigations had found midazolam reduced expression of a key circadian rhythm protein known to protect the heart from damage. So Eckle and colleagues took a closer look at nearly two million health records to see if the rates of post-operative heart complications in patients administered midazolam differed depending on the time of the day surgery was performed.
“We performed a large dataset analysis and demonstrated that administering midazolam is associated with an increased risk of myocardial injury in non-cardiac surgery when surgeries occurred at night and in healthier patients,” Eckle said. "That suggests midazolam interferes with the circadian system in humans."
The analysis divided surgical procedures between day (6 am to 6 pm) and night (6pm to 6am). In healthy patients, the results were stark, with those patients given midazolam during night surgeries three times more likely to suffer heart damage.
More work is needed to better understand this specific midazolam circadian relationship, but Eckle does indicate the findings are a strong example of the importance of considering what time of day drugs are effective. It may be challenging to retroactively establish optimal times to administer the hundreds of drugs currently used, but it has been suggested that research into new medicines take into account circadian rhythms.
“Drugs are often administered according to what’s most efficient,” added Eckle. “But what is most efficient, may in the end cause damage.”
The new study was published in Frontiers in Cardiovascular Medicine.