Many Commonly Prescribed Medications Linked to Risk of Concurrent Depression

We touched base with Dr. Mark Olfson to discuss his intriguing new original investigation in JAMA, “Prevalence of Prescription Medications With Depression as a Potential Adverse Effect Among Adults in the United States.”

Dr. Olfson is a Professor of Psychiatry and Epidemiology at Columbia University Irving Medical Center (CUIMC) and a Research Psychiatrist at the New York State Psychiatric Institute (NYSPI). His research focuses on identifying gaps between clinical science and practice in the delivery of mental health care with a focus on the safety and effectiveness of treatments provided in routine practice.

Columbia Psychiatry: What is the main finding of your new research, “Prevalence of Prescription Medications With Depression as a Potential Adverse Effect Among Adults in the United States”?

Dr. Olfson: I think the most important findings are that more than a third of US adults are using medications that either have a potential to cause to depression or increase the risk of suicide. One reason that this is important is that adults who were taking these medications were at increased risk of actually having depression and the more of these medications people were taking, the greater was their risk. 

Columbia Psychiatry: How did you become involved in this study?

Dr. Olfson: I have been involved in studying national patterns and trends in use of psychiatric medications and depression for many years. Dima Qato at the UIC College of Pharmacy knew my work and reached out to me with the idea of studying use of not just one class of medications with depression adverse effects but studying all of them as a sort of super class of medications. This idea struck me as novel and so over the next several months we worked together on developing a strategy to assess national patterns in use of prescription medications with depression as a potential adverse effect and then evaluate whether use of these medications was associated with depression.  

Columbia Psychiatry: Briefly describe the methods to your key findings. 

Dr. Olfson: We analyzed data from the National Health and Nutrition Examination Survey focusing on adults who use medications with depression as a possible adverse effect. The survey also includes a standard set of questions, the Patient Health Questionnaire-9, to assess depression. Our results revealed that the percentage of US adults taking one or more of these medications in the last 30 days increased from 35.0% in 2005-2006 to 38.4% in 2013-2014. In analyses that controlled for a wide range of potential clinical and demographic confounding factors, the adjusted percentage of adults with depression increased from those taking none (4.7%), one (6.9%), two (9.5%), to three or more (15.3%) medications with a potential for depression as side-effect. 

Columbia Psychiatry: Did the findings surprise you at all?

Dr. Olfson: Given the substantial number of medications that have been linked to depression as an adverse effect and the aging population, I expected that a large and growing percentage of US adults would be using these medications. However, I was surprised to see the significant and graded association between using these medications and risk of concurrent depression. It is one thing to observe depression as an adverse effect in clinical research and quite another to see correlations between using these medications and depression in the general US adult population.

Columbia Psychiatry: What kinds of prescription drugs have depression listed as a potential side effect? Also, what other side effects do these drugs list?

Dr. Olfson: Over 200 different medications have depression as a potential adverse effect and therefore were included in our study. These include some analgesics (pain killers), some anticonvulsants (anti-seizure medications), beta blockers used to treat hypertension, proton pump inhibitors used to treat peptic ulcers, some birth control pills, and many other medications.  

Columbia Psychiatry: What are some of the implications of this new investigation?

Dr. Olfson: Many patients and physicians may not be aware that many commonly used medications are associated with an increased risk of depression. The new results suggest that physicians and other health care professionals should consider discussing these associations with their patients who are prescribed these medications. This may be particularly important if the patient has a history of depression or a related psychiatric disorder.

The clinical decision to discuss these associations should also consider the risks of unintended negative psychological effects similar to a negative placebo effect, sometimes call the “nocebo effect.” In these discussions, it is important for physicians to strike a balance between potential desired effects of the medications and the risks of adverse effects and to address patients’ expectations and concerns regarding the potential for depression adverse effects.

Columbia Psychiatry: Is depression a public health issue?

Dr. Olfson: Depression, which affects more than one in twenty US adults each year, is a major public health concern. It is a leading source of disability, work loss, and health care expenditure. The new findings suggest that use of medications with depression side effects may contribute to the national public health burden of depression, especially among women, older adults, unemployed adults, and adults with chronic medical conditions who were all especially likely to use these medications.  

Columbia Psychiatry: Where does the research go from here? 

Dr. Olfson: An important next step in this line of research will be to examine whether people who are prescribed these medications are at risk over time of developing depression. Studying these associations over time would help to address an important limitation of this research: we were not able to examine whether the use of medications with depression as an adverse effect preceded development of depression. 

Columbia Psychiatry: What is next on the docket from your team?

Dr. Olfson: We are considering future research that would take advantage of electronic medical records within large health care systems that routinely monitor depressive symptoms and medication prescriptions to better understand the clinical contexts within which commonly prescribed medications have a potential to cause depression.  

Columbia Psychiatry: Is there anything else you’d like to highlight about your work or about any potentially future work with Dima M. Qato and Katharine Ozenberger?

Dr. Olfson: Primary care physicians often practice under considerable time pressure. Once a patient is identified as having depression, patients are commonly presented with options of either starting antidepressants or psychotherapy. It is my hope that the new findings will lead primary care physicians to first consider whether one or more of the medications we studied is contributing to the patient’s depression.  


The authors of “Prevalence of Prescription Medications With Depression as a Potential Adverse Effect Among Adults in the United States” are: Dima M. Qato, PharmD, PhD (Department of Pharmacy Systems, Outcomes and Policy, University of Illinois at Chicago, and Division of Epidemiology and Biostatistics, University of Illinois at Chicago School of Public Health); Katharine Ozenberger, MS (Department of Pharmacy Systems, Outcomes and Policy, University of Illinois at Chicago); and Mark Olfson, MD, MPH (Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center).