Wednesday, August 10, 2022
HomeWeekly RoundupResearchers look for links between prescription drugs and depression

Researchers look for links between prescription drugs and depression

Could your medications be making you depressed asks a US study by researchers at the University of Illinois at Chicago, College of Pharmacy, University of Illinois at Chicago School of Public Health and the College of Physicians and Surgeons, Columbia University, looking into possible links between prescription drugs and depression.

According to a UK National Health Service (NHS) statement, researchers looked at prescriptions issued to 26,192 adults in the US between 2005 and 2014. They found that more than a third had used medicines with depression as a possible side effect. The results showed that around 1 in 7 people had depression among those taking 3 or more such medicines, compared to around 1 in 20 among those not taking any medicines linked to depression.

There are reasons to be cautious about the findings, however, the NHS says. Many medicines have a long list of potential side effects, which doesn't mean that everyone taking them will get any or all of those side effects. Also, people taking 3 or more medicines are more likely to have a long-term condition than people taking no medicines. Having a long-term health condition is known to increase the risk of depression, regardless of any medication side effects.

If you are feeling down, it's a good idea to talk to your doctor. One of the things they can consider is whether any of the medicines you are taking could be contributing to the problem.

The NHS says BBC News' report of the study was broadly accurate and balanced. The Mail Online claimed people were unaware that their medications' potential side effects included depression, although nothing in the study suggests this is the case. The Mail Online also misreported the figures, saying at one point that nearly 25% of people studied were taking 3 or more drugs linked to depression and at another point that this figure was 35%, when the true figure was 7.5%.

This was a cross-sectional study of a sample of the US population. Cross-sectional studies are good at establishing links between factors seen in large populations. However, they cannot show that one factor (such as medication use) directly causes another (such as depression), partly because they cannot show which happened first.

Researchers used data from the US National Health and Nutrition Examination Survey (NHANES). This is sent to a random representative sample of US adults every 2 years. They used data collected from 5 surveys carried out from 2005 to 2006 and 2013 to 2014.

The survey included questions about all the prescription medicines taken over the previous 30 days, and a questionnaire to assess depression symptoms. After excluding people with missing data, researchers had results from 26,192 people.

They then checked to see: how many people were taking 0, 1, 2 or 3 drugs associated with depression as a possible side effect; and for each of these groups, how many people had depression.

Researchers also looked at how many people were taking drugs not associated with depression, and whether that was linked to how many of them had depression. They did different analyses looking separately at people taking antidepressants, and at people with high blood pressure who were on specific drugs, as some blood pressure drugs, such as beta-blockers, are known to be linked to depression.

They adjusted their figures to take account of the following confounding factors: sex; age; ethnic background; marital status; employment status; educational achievement; family income; body mass index; and number of long-term conditions.

The results were in total, 37% of people surveyed had taken at least 1 prescription drug associated with depression in the previous 30 days: 62.8% did not use any drug associated with depression; 21% used 1 drug associated with depression; 8.7% used 2 drugs associated with depression; and 7.5% used 3 or more drugs associated with depression.

People taking these medicines were more likely to be 65 or older, female, widowed, and have a higher number of long-term health problems. People who took more drugs with depression as a possible side effect were more likely to have depression.

After taking account of potential confounding factors, the percentage of people with depression was: 4.7% of people using no drugs with depression as a side effect; 6.9% of people using 1 drug with depression as a side effect; 9.5% of people using 2 drugs with depression as a side effect; and 15.3% of people using 3 or more drugs with depression as a side effect.

However, when researchers looked at medicines not associated with depression, they found no link between the number of medications taken and depression.

The drug combinations most associated with depression included the beta-blockers metoprolol and atenolol, the proton pump inhibitor omeprazole, the pain relief drug hydrocodone, and gabapentin, a drug used to treat epilepsy as well as nerve pain.

According to the NHS, when interpreting the results, the researchers said their results showed that "reported use of prescription medications as a potential adverse effect was common" and that using several of these drugs "was associated with a greater likelihood of concurrent depression". They said 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".

The NHS says reading the list of potential side effects on a medicine leaflet can be daunting, and the reports of this study may also cause alarm. The first thing to remember is that not everyone gets side effects associated with a medicine. If you are taking a medicine with depression as a side effect, but you are not depressed, there's nothing to worry about.

Depression is a complex condition and many factors can contribute to someone becoming depressed. This includes having a long-term health condition, which makes it difficult to work out whether the condition or the medicines used to treat it are a cause of depression.

However, the NHS says, the study is a useful reminder that some medicines can contribute to depression, including those that are prescribed for conditions you would think had nothing to do with low mood. Examples include hormonal contraceptives, drugs to lower blood pressure, painkillers, drugs used to treat respiratory diseases such as asthma, and drugs to control stomach acid.

The study has some limitations: all the information was from US adults; rates of prescription for depression-linked drugs may be different in the US, as well as rates of depression; the cross-sectional design of the study means we don't know whether people started taking the drugs before becoming depressed, or afterwards; and the study didn't measure whether people had a history of past depression.

Also, the study only looked at prescription medications, while some drugs linked to depression are available over-the-counter in the US.

The NHS says people should not suddenly stop taking any prescribed medication as this could be potentially dangerous. If there is concern about side effects of any medicines, whether prescribed or over-the-counter, the advice is speak to a GP or pharmacist.


BBC News reports that UK experts cautioned that the paper shows an association between taking these drugs and an increased risk of depression but not cause and effect. Professor David Baldwin, from the Royal College of Psychiatrists, said: "It is not surprising that using medicines to treat physical illnesses such as heart and lung disease should be associated with depressive symptoms, as these physical illnesses are themselves linked to an increased risk of depression."

The Royal College of GPs also pointed out that not all of the findings will necessarily apply to the UK, as the health system is different in the US. Nevertheless, its chair, Professor Helen Stokes-Lampard, added that it shows "how vital it is that patients disclose any medication they may be taking that the GP might not be aware of, or to the pharmacist if buying medication over the counter".

Importance: Prescription medications are increasingly used among adults in the United States and many have a potential for causing depression.
Objectives: To characterize use of prescription medications with depression as a potential adverse effect and to assess associations between their use and concurrent depression.
Design, Setting, and Participants: Five 2-year cycles (2005-2006 through 2013-2014) of the National Health and Nutrition Examination Survey, representative cross-sectional surveys of US adults aged 18 years or older, were analyzed for use of medications with depression as a potential adverse effect. Multivariable logistic regression examined associations between use of these medications and concurrent depression. Analyses were performed among adults overall, excluding antidepressant users, and among adults treated with antidepressants and with hypertension.
Exposures: Prescription medications with depression as a potential adverse effect (listed in Micromedex).
Main Outcomes and Measures: Prevalence of any use and concurrent use of medications with a potential to cause depression and prevalence of depression (PHQ-9 score ≥10).
Results: The study included 26 192 adults (mean age, 46.2 years [95% CI, 45.6-46.7]; women, 51.1%) and 7.6% (95% CI, 7.1%-8.2%) reported depression. The overall estimated prevalence of use of medications with depression as an adverse effect was 37.2%, increasing from 35.0% (95% CI, 32.2%-37.9%) in the cycle years 2005 and 2006 to 38.4% (95% CI, 36.5%-40.3%) in 2013 and 2014 (P for trend = .03). An estimated 6.9% (95% CI, 6.2%-7.6%) reported use of 3 or more concurrent medications with a potential for depression as an adverse effect in 2005 and 2006 and 9.5% (95% CI, 8.4%-10.7%) reported such use in 2013 and 2014 (P for trend = .001). In adjusted analyses excluding users of antidepressants, the number of medications used with depression as possible adverse effects was associated with increased prevalence of concurrent depression. The estimated prevalence of depression was 15% for those reporting use of 3 or more medications with depression as an adverse effect vs 4.7% for those not using such medications (difference, 10.7% [95% CI, 7.2%-14.1%]). These patterns persisted in analyses restricted to adults treated with antidepressants, among hypertensive adults, and after excluding users of any psychotropic medication.
Conclusions and Relevance: In this cross-sectional survey study, use of prescription medications that have depression as a potential adverse effect was common. Use of multiple medications was associated with greater likelihood of concurrent depression.

Dima Mazen Qato; Katharine Ozenberger; Mark Olfson

[link url=""]NHS statement[/link]
[link url=""]BBC News report[/link]
[link url=""]JAMA abstract[/link]

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