Medications with depression as a possible adverse effect associated with increased depression risk

1. In this cross-sectional study, the use of medications with depression as an adverse effect was associated with a higher prevalence of depression while a similar association was not observed for medications without depression as a possible side effect.

2. More US adults are taking medications with depression or suicide as a possible adverse effect over the last decade.

Evidence Rating: 3 (Fair)

Study Rundown: In the US, there are over 200 medications that have depression reported as a possible side effect, with antihypertensives, proton pump inhibitors, analgesics, and hormonal contraceptives being the most common. Despite these possible risks, it is unclear how real world use of these medications influences the prevalence of depression. In this cross-sectional study, the use medications with depression as a possible adverse effect was associated with a higher prevalence of depression. By contrast, a similar association with rising depression prevalence was not observed for medications without depression as a possible side effect. For patients taking medications with suicide as a possible adverse effect, there was also an increase in the prevalence of depression. More US adults are taking medications with depression or suicide as a possible adverse effect over the last decade.

While this association suggests increased awareness of depression as a possible adverse effect may be beneficial for practitioners, many limitations make this association difficult to interpret. Most importantly, due to limitations in the data set, it is not clear how the use of these medications and the development of depression are associated in time, and the alternative hypothesis that patients with depression are more likely to need these medications for other reasons cannot be excluded. In addition, the past history of depression and other psychiatric co-morbidities could not be taken into account in this study, which would be informative in terms of assessing risk. Still, an argument for inclusion of these medications in screening instruments for depression is supported by this study, and further investigations may support a specific role for this practice.

Click to read the study in JAMA

Relevant Reading: Use of proton-pump inhibitors is associated with depression: a population-based study

In-Depth [cross-sectional study]: This study utilized data on 26 192 participants from the National Health And Nutritional Examination Survey (NHANES) from the 5 most recent 2-year cycles (2005-2006, 2007-2008, 2009-2010, 2011-2012, and 2013-2014). A score of 10 or more on the Patient Health Questionnaire 9 (PHQ-9) was used to establish the prevalence of depression. Using Micromedex, medications with depression as a possible adverse effect were defined as those associated with ‘depression’, ‘depressive disorder’, ‘suicide’, ‘suicidal thoughts’, ‘suicidal ideation’, or ‘suicidal behavior’. Medications with ‘Suicide’, ‘suicidal thoughts’, ‘suicidal ideation’, and ‘suicidal behavior’ as adverse effects were classified as suicidal adverse effects.

About 37.2% (CI₉₅ 36.0 to 38.3%) of patients were prescribed at least 1 medications with depression as a possible adverse effect with older age (≥65 years), female sex, widowed marital status, and a higher number of chronic conditions being associated with use of these medications (p < 0.05). Use of medications with depression as a possible adverse effect increased from 35.0% (CI₉₅ 32.2 to 37.9%) in 2005-2006 to 38.4% (CI₉₅ 36.5 to 40.3%) in 2013-2014 with use of 3 or more of these prescription medications increasing from 6.9% (CI₉₅ 6.2% to 7.6%) to 9.5% (CI₉₅ 8.4 to 10.7%). Use of medications with suicidal symptoms as possible adverse effects increased from 17.3% (CI₉₅ 15.9 to 18.8%) in 2005-2006 to 23.5% (CI₉₅ 21.8 to 25.2%) in 2013-2014. Medications with depression as a possible adverse effect were associated with increased risk of depression when patients were taking 1 (Adjusted Difference 2.2%; CI₉₅ 0.8 to 3.6%), 2 (4.9%; CI₉₅ 2.8 to 6.9%), and 3 or more of these medications (10.7%; CI₉₅ 7.2 to 14.1%). This association was not observed for medications without depression as a possible adverse effect regardless of the number of medications (p > 0.05). For medications with suicidal symptoms as possible adverse effects, there was an increased risk of depression for those taking 1 (3.1%; CI₉₅ 1.3 to 4.8%), 2 (7.0%; CI₉₅ 2.9 to 11.1%), and 3 of these medications (12.5%; CI₉₅ 1.7 to 23.4%). Multiple sensitivity analyses were completed without a change in these results.

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