Prescription Medications with Depression As Potential Adverse Effect Is Common

This is the first study to demonstrate that prescription drugs were often used concurrently, and that polypharmacy was associated with a greater likelihood of experiencing depression.

Dima Qato, PharmD, PhD, MPH

In a recently published cross-sectional survey study, University of Illinois at Chicago researchers concluded that an estimated 37% of US adults use prescription medications that include depression as a possible side effect, which is associated with a greater likelihood of concurrent depression.

Prescription medications are widely used among adults and many prescriptions like hormonal contraceptives and beta-blockers are associated with an increased risk of depression or suicide.

This is the first study to demonstrate that prescriptions drugs were often used concurrently, and that polypharmacy was associated with a greater likelihood of experiencing depression.

“The use of multiple medications associated with a potential risk for depression or suicidal symptoms is increasing and may be contributing to the growing problem of depression, including treatment-resistant depression, and increasing rates of suicide in the US,” Dima Qato, PharmD, PhD, MPH, assistant professor of pharmacy systems, outcomes and policy, UIC College of Pharmacy, told MD Magazine. “Health care professionals should consider discussing the potential risk of depressive or suicidal symptoms with their patients who are prescribed medications that carry these side effects.”

Researchers retrospectively analyzed medication use patterns with depression as a potential adverse effect in 26,192 adults (aged 18 years or older) with a mean age of 46.2 years who participated in the National Health and Nutrition Examination Survey between 2005—2014. Among the study population, 51.1% were women and 7.6% reported depression during the study period.

Multivariable logistic regression examined associations between use of medications and concurrent depression. Researchers performed analyses among adults and excluded antidepressant users and those treated with antidepressants and with hypertension.

Use of prescription medications with a potential adverse effect of depression was defined as a categorical variable (0, 1, 2, or ≥3 prescription medications that have a potential for an adverse effect of depression), while concurrent use was defined as the use of 2, 3 or more medications that have a potential for depression as an adverse effect. Medications with depression, depressive disorder, suicide, suicidal thoughts, suicidal ideation or suicidal behavior listed as common or serious adverse effects were defined as possibly having depression as an adverse effect.

An estimated 62.8% (95% CI, 61.7%-64.0%) of adults reported no use of any prescription medication that had depression as a potential adverse effect in the prior 30 days, whereas an estimated 37.2% (95% CI, 36.0%-38.3%) used at least 1.

The reported use of any prescription medication that had depression as a potential adverse effect increased from 35% (95% CI, 32.2%—37.9%) in 2005 and 2006 to 38.4% (95% CI, 36.5%–40.3%) in 2013 and 2014 ( P for trend = .03). Concurrent use of 3 or more medications increased from 6.9% (95% CI, 6.2%—7.6%%) in 2005 and 2006 to 9.5% (95% CI, 8.4%–10.7%) in 2013 and 2014 (P for trend = .001).

For patients taking 1 prescription medication, the estimated prevalence of depression increased from 6/9% to 15.3% for those taking 3 or more medications with depression as potential adverse effect compared to 4.7%, for those not using such medications (difference, 10.7% [95% CI, 7.2%—14.1%]).

Researchers concluded that not only was use of prescription medications that have depression as a potential adverse effect common, but use of multiple medications was associated with a greater likelihood of concurrent depression. The study reported that the likelihood of concurrent depression was most pronounced among adults concurrently using 3 or more medications with depression as a potential adverse effect, including among adults treated with antidepressants. Concurrent use of medications, however, that do not have depression as a potential adverse effect was not associated with concurrent depression.

“Since commonly used screening tools do not incorporate information on prescription medications with a potential to cause depression, it is important that physicians follow positive screens with an assessment of these medication-related risks,” Qato added. “For some patients, this may involve revising their medication regimen (e.g. de-prescribing medication(s) with depression as a side effect and/or using an alternative medication) before initiating an antidepressant or psychotherapy.”

Similar results were observed for drugs that listed suicide as a potential side effect. Researchers found that these findings persisted when those using psychotropic medications were excluded. Suicide, suicidal thoughts, suicidal ideation and suicidal behavior were further subclassified as having suicidal symptoms as adverse effects.

The study highlights an important trend of increasing polypharmacy for medications associated with depression, especially suicidal symptoms, as a possible adverse effect.

“Patients and health care providers need to be aware of the risk of depression, including suicidal symptoms, that comes with commonly used prescription drugs—many of which are also available over-the-counter,” concluded Qato. “Increasing awareness is particularly important considering the growing rates of polypharmacy for medications with depression as potential side effect.”

When studying prescription drugs with suicide listed as a potential adverse effect, usage 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, and concurrent use of 3 or more drugs significantly increased from 1.9% (95% CI, 1.5%–2.2%) in 2005 and 2006 to 3.3% (95% CI, 2.8%–4.0%) in 2013 and 2014.

Further longitudinal studies are needed to examine whether providing information about medications that have been associated with depression as a potential adverse effect to patients will decrease the succeeding incidence of depression.

The study "Prevalence of Prescription Medications With Depression as a Potential Adverse Effect Among Adults in the United States" was published in JAMA June 12, 2018.