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New Research Shows Drugs Associated with a Risk of Depression Are Widely Used

Worst Pills, Best Pills Newsletter article October, 2018

Major depression is a common mood disorder that is estimated to have afflicted more than 16 million adults in the U.S. in 2016.[1] Importantly, the drugs in your medicine cabinet may be one cause of depression symptoms, including suicidal thoughts or behavior. If so, the remedy might be, in consultation with your doctor, to stop the drug causing depression rather than starting an antidepressant to treat this drug-induced disease.

A well-designed study recently published in the Journal...

Major depression is a common mood disorder that is estimated to have afflicted more than 16 million adults in the U.S. in 2016.[1] Importantly, the drugs in your medicine cabinet may be one cause of depression symptoms, including suicidal thoughts or behavior. If so, the remedy might be, in consultation with your doctor, to stop the drug causing depression rather than starting an antidepressant to treat this drug-induced disease.

A well-designed study recently published in the Journal of the American Medical Association (JAMA) showed that use of medications that have depression as a potential adverse effect is very common.[2] Moreover, when patients use more than one of these medications at the same time, their risk of having depression symptoms increases significantly.

Identifying drugs linked to depression

The JAMA study researchers searched a prescription drug database called Micromedex, which contains information about adverse effects described in the Food and Drug Administration (FDA)-approved product labeling for prescription medications.

From the Micromedex database, they identified all prescription drugs that had any of the following listed as a common or serious adverse event: depression, depressive disorder, suicide, suicidal thoughts, suicidal ideation or suicidal behavior. Such drugs were considered to have a potential for depression as an adverse effect.

Most commonly used drugs linked to depression

To estimate how often U.S. adults use prescription drugs with depression as a potential adverse effect, the JAMA study researchers analyzed data collected from more than 26,000 adults age 18 or older who participated in the U.S. National Center for Health Statistics’ National Health and Nutrition Examination Surveys (NHANES) for the following two-year cycles: 2005-2006, 2007-2008, 2009-2010, 2011-2012 and 2013-2014. The NHANES is a nationally representative health survey of people living in communities across the U.S. (see text box, below, to learn more about the NHANES program).

The survey questions completed by the NHANES participants included standardized questions about depression symptoms experienced during the previous two weeks. Such questions are routinely used for diagnosing depression. Information on use of prescription medications also was collected during in-person interviews at the participants’ homes. The participants were asked to show the NHANES interviewers containers for all prescription medications taken during the prior 30 days.

Based on survey data from 2005 to 2014, the researchers estimated that more than one-third of U.S. adults used at least one drug that has depression as a potential common or serious adverse effect. Factors associated with use of such drugs included age greater than 64, female sex, widowed marital status and a higher number of chronic medical conditions. Overall, an estimated 8 percent of adults reported depression over the entire study period.

The estimated number of adults who used at least one of these drugs increased slightly from 35 percent in 2005-2006 to 38 percent in 2013-2014. Concurrent use of three or more such drugs increased from 7 percent in 2005-2006 to 10 percent in 2013-2014. Any use of prescription medications that have suicidal symptoms as potential adverse effects increased from 17 percent in 2005-2006 to 24 percent in 2013-2014.

The most commonly used class of drugs that have depression as a potential adverse effect was antidepressants. In 2013-2014, an estimated 15 percent of adults used one or more antidepressants, up from 11 percent of adults in 2005-2006.

The list of the most commonly used drugs that have depression as a potential common or serious adverse effect also included allergy/asthma drugs, analgesics, antihypertensives (drugs for treating high blood pressure), corticosteroids (also known as glucocorticoids), gastrointestinal drugs that suppress stomach acid, hormones/hormone modifiers, sedatives/insomnia drugs and seizure drugs (see Table, below).

In an analysis that excluded people who were currently using antidepressants, the JAMA study researchers found that as the number of concurrently used medications with depression as an adverse effect increased, the proportion of those who met criteria for depression during the prior two weeks on the NHANES survey increased. Among people not using any such drugs, 5 percent had depression symptoms. Among those using one, two, or three or more such drugs, the proportions with depression symptoms were 7, 10 and 15 percent, respectively. A similar analysis that looked at number of concurrently used drugs not having depression as an adverse effect found no such association with depression symptoms.

Most Commonly Used Oral Medications with Depression as a Potential Adverse Effect Among U.S. Adults†

Generic Name Brand Name(s)
Allergy/Asthma Drugs
montelukast* SINGULAIR
cetirizine** ZYRTEC ALLERGY, ZYRTEC HIVES RELIEF, ZYRTEC-D 12 HOUR***
Analgesics
hydrocodone ANEXSIA,*** HYSINGLA, NORCO,*** REPREXAIN,*** ZOHYDRO ER*
tramadol* CONZIP, ULTRACET,*** ULTRAM
ibuprofen ADVIL, IBU-TAB, MOTRIN IB, PROFEN
Antidepressants
sertraline** ZOLOFT
citalopram** CELEXA
bupropion** APLENZIN, FORFIVO XL, WELLBUTRIN SR, WELLBUTRIN XL
fluoxetine** PROZAC, SARAFEM, SELFEMRA, SYMBYAX***
trazodone* generic only
venlafaxine** EFFEXOR XR
escitalopram** LEXAPRO
duloxetine* CYMBALTA
paroxetine** PAXIL, PEXEVA
amitriptyline* generic only
Antihypertensives (Drugs for Treating High Blood Pressure)
metoprolol DUTOPROL,*** LOPRESSOR, LOPRESSOR HCT,*** TOPROL-XL
atenolol TENORETIC,*** TENORMIN
enalapril** EPANED, VASERETIC,*** VASOTEC
quinapril** ACCUPRIL, ACCURETIC,*** QUINARETIC***
Gastrointestinal Drugs That Suppress Stomach Acid
omeprazole** PRILOSEC, ZEGERID***
ranitidine ZANTAC
esomeprazole** NEXIUM
famotidine PEPCID
Hormones/Hormone Modifiers
ethinyl estradiol Found in multiple combination birth control pills
estradiol Found in multiple combination birth control pills
finasteride* PROPECIA, PROSCAR
Muscle Relaxants
cyclobenzaprine* AMRIX
Sedatives/Insomnia Drugs
alprazolam**** XANAX
zolpidem* AMBIEN, EDLUAR, INTERMEZZO
lorazepam* ATIVAN
diazepam* DIASTAT, VALIUM
Seizure Drugs
gabapentin** GRALISE, HORIZANT, NEURONTIN
clonazepam KLONOPIN
lamotrigine LAMICTAL
topiramate** QUDEXY XR, TOPAMAX

†Drugs are listed in order from most commonly used to least commonly used as of 2013-2014.
*Designated as Do Not Use
**Designated as Limited Use
***Combination drug containing other active ingredients
****Designated as Do Not Use Except for Panic Disorder

The National Health and Nutrition Examination Survey (NHANES)*

NHANES is a program of studies designed to assess the health and nutritional status of adults and children in the U.S.[3] The program is run by the National Center for Health Statistics, a part of the Centers for Disease Control and Prevention (CDC).

The NHANES program began in the early 1960s and has involved a series of surveys that focus on different population groups or health issues. Each survey collects data on a nationally representative sample of about 5,000 people per year. These people are located in counties across the country, 15 of which are visited each year.

The program is unique in that it combines in-person interviews with physical examinations. The interviews include detailed questions about demographics, socioeconomic status, diet and health status, including use of prescription and over-the-counter medications. Medical, dental and physiological measurements are taken, and a variety of laboratory tests are performed.

Findings from the surveys are used to estimate how many people in the U.S. have major diseases and to determine the risk factors for these diseases, including lifestyle factors (such as smoking, diet and exercise), hereditary background and environmental exposures. NHANES findings also form the basis for national standards for such measurements as height, weight and blood pressure.

Researchers at the CDC, the National Institutes of Health and the FDA, as well as at universities and academic medical centers throughout the world, use the NHANES data for a wide array of important epidemiological and other research.

*Source: National Center for Health Statistics, Centers for Disease Control and Prevention

What You Can Do

When starting a new medication that is known to have depression as an adverse effect, you should always be vigilant about this risk. If you develop symptoms of depression, including suicidal thoughts, while taking any such medication, consult your doctor. Your evaluation should include an assessment of whether your symptoms may be related to any medications that you are taking currently. Do not stop taking any medication without talking to your health care professional first.


References

[1]National Institute of Mental Health. Major depression. November 2017. https://www.nimh.nih.gov/health/statistics/major-depression.shtml. Accessed August 5, 2018.

[2]Qato DM, Ozenberger K, Olfson M. Prevalence of prescription medications with depression as a potential adverse effect among adults in the United States. JAMA. 2018;319(22):2289-2298.

[3]Centers for Disease Control and Prevention, National Center for Health Statistics. About the National Health and Nutrition Examination Survey. September 15, 2017. https://www.cdc.gov/nchs/nhanes/about_nhanes.htm. Accessed August 5, 2018.