More than one-third of US adults use prescription medications that have depression as a potential adverse effect, and those taking more than one such drugs run a greater risk of concurrent depression, a large population-based survey shows

The cross-sectional study, published online June 12 in JAMA, used data from National Health and Nutrition Examination Survey participants in the five most recent 2-year survey cycles, conducted between 2005 and 2014. The researchers identified medications potentially causing depression and suicidal symptoms through Micromedex (Truven Health Analytics).

The study cohort consisted of 26,192 adults, 51.1% women, with a mean age of 46.2 years. Respondents reported using more than 200 drugs associated with depression or suicidal ideation, and overall, 7.6% of adults in the cohort reported depression during the study period, as defined by a score of 10 or higher on the Patient Health Questionnaire 9.

The researchers found an overall estimated prevalence of using depression-associated medications in the last 30 days of 37.2% (95% confidence interval [CI], 36.0% – 38.3%). Moreover, the prevalence increased from 35.0% (95% CI, 32.2% – 37.9%) in the earliest National Health and Nutrition Examination Survey cycle (2005-2006) to 38.4% (95% CI, 36.5% – 40.3%) in the latest one (2013-2014; P for trend = .03).

Commonly used medications that have depression as a possible adverse effect include antihypertensives such as beta-blockers, proton pump inhibitors, analgesics, and hormonal contraceptives.

"The results suggest that physicians should consider discussing these associations with their patients who are prescribed medications that have depression as a potential adverse effect," write Dima Mazen Qato, PharmD, MPH, Ph.D., an assistant professor at the University of Illinois at Chicago's College of Pharmacy, and colleagues.


In addition, the researchers found a rise in the concomitant use of three or more of these drugs during the study, from 6.9% (95% CI, 6.2% – 7.6%) to 9.5% (95% CI, 8.4% – 10.7%).

The use of prescription medications causing potential suicidal symptoms also increased from 17.3% (95% CI, 15.9% – 18.8%) in 2005 and 2006 to 23.5% (95% CI, 21.8% – 25.2%) in 2013 and 2014.

The researchers also found that the estimated prevalence of concurrent depression rose with multiple medications, increasing from 6.9% (95% CI, 6.2% – 7.6%) for those taking one potentially depressant agent to 15.3% (95% CI, 12.0% – 18.6%) for those taking at least three compared with a prevalence of 4.7% for patients not using such medications.

Potentially depressive medication use was significantly associated with age 65 years and older, female sex, widowed marital status, and a greater number of chronic comorbidities.

"For some patients, this may involve revising their medication regimen; for example, deprescribing or using an alternative medication that doesn't have depression as a side effect, before initiating an antidepressant or psychotherapy," Qato told Medscape Medical News.

"And in patients already being treated with antidepressants but not responding to treatment, it is important to evaluate the potential role of the concurrent use of additional medications that can cause depression."

The authors also note that proton pump inhibitors and the emergency contraceptive levonorgestrel can be purchased as over-the-counter products, which lack comprehensive labeling information on adverse effects.

"Many patients may therefore not be aware of the greater likelihood of concurrent depression associated with these commonly used medications," they write. They call for longitudinal studies on whether providing information about depression-associated medications will reduce incidence.