More than a third of adults in the United States may be taking prescription medications that have depression or suicidal thoughts as possible side effects, according to a study published Tuesday in the Journal of the American Medical Association (JAMA).

The study also found that people who take these medications are more likely to be depressed than those not taking them — and the risk increases with each additional drug they’re prescribed. 

This is the first study to show that the concurrent use of prescription drugs — a situation known medically as polypharmacy — heightens the risk of developing depression.

The finding is troubling, particularly given that drugs with either depression or suicidal thoughts as potential side effects are some of the most commonly prescribed medications in the United States. They include birth control pills, proton pump inhibitors to treat acid reflux, beta blockers for high blood pressure, anticonvulsants, corticosteroids and painkillers (including ibuprofen).  

“Many may be surprised to learn that their medications, despite having nothing to do with mood or anxiety or any other condition normally associated with depression, can increase their risk of experiencing depressive symptoms, and may lead to a depression diagnosis,” said Dima Qato, the study’s lead author and a pharmacy researcher and assistant professor at the University of Illinois at Chicago, in a released statement.  

Study details

For the study, Quato and her colleagues analyzed information provided by more than 26,000 U.S. adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 2005 through 2014. As part of the survey, participants listed all the medications they were taking and completed a questionnaire designed to screen for depression. The mean age of the participants was 46 years, and slightly more than half were women. 

The survey revealed that 7.6 percent of the participants had depression. It also found that 38.4 percent of all the participants were taking at least one of 200-plus medications that have depression as a potential side effect in 2013-2014, up from 35 percent in 2005-2006.

Qato and her colleagues then analyzed the data to see if there was an association between taking those medications and an increased risk of depression. They found that the prevalence of depression was greater among the people who took the drugs than among those who didn’t — with the risk climbing as more of the drugs were taken concurrently. 

Among people who were taking one of the medications that could cause depression, 6.9 percent had depression, compared to 4.6 percent of those not using any of them. The proportion rose to 9.5 percent for people taking two of the medications, and then jumped to 15.3 percent for those taking three or more.

Similar associations were found among the participants who were taking medications that have suicidal symptoms as a potential side effect. 

The findings reflect statistical adjustments made by the researchers to account for demographic factors known to cause depression, such as poverty, marital status and unemployment, as well as for medical conditions associated with depression, such as chronic pain.

The study’s results also held after the researchers excluded participants who were taking medications specifically used to treat psychiatric conditions.

A growing problem

This study is observational, which means it can’t prove a cause-and-effect relationship between the use of prescription medications and depression. 

Still, the findings are supported by previous research that has found links between depression and specific classes of prescription medications, such as proton pump inhibitors and hormonal contraceptives.

One of the more concerning findings in the current study involves the increasing number of Americans who are taking multiple medications with depression and suicidal thoughts as potential side effects. In 2005-2006, about 7 percent of American adults were concurrently taking three or more of drugs with depression listed as a potential side effect. That jumped to 10 percent in 2013-2014.

The percentage of Americans taking three or more drugs that have suicidal thoughts listed as a potential side effect also increased — from 2 percent in 2005-2006 to 3 percent in 2013-2014.

“People are not only increasingly using these medicines alone, but are increasingly using them simultaneously, yet very few of these drugs have warning labels,” said Qato. “So until we have public or system-level solutions, it is left up to patients and health care professionals to be aware of the risks.”

Physicians should consider assessing the medications their patients are taking when they screen them for depression, she and her colleagues urge in their paper.

And patients should talk with their doctors if they notice any changes in their mood while taking a medication. Sometimes another drug can be prescribed. 

“With depression as one of the leading causes of disability and increasing national suicide rates, we need to think innovatively about depression as a public health issue,” said Qato. 

FMI:You’ll find an abstract of the study on the JAMA website, but the full study is behind a paywall.