Older Patients With Depression at Risk of Polypharmacy

A study conducted in the Netherlands found older adults with depression were at greater risk of polypharmacy than those without depression.

Findings of a longitudinal observational study carried out in the Netherlands revealed depression moderates polypharmacy in older patients through shared risk factors like motivational problems (ie, apathy), anxiety, and pain.

“These 3 symptom dimensions hold a complex relationship or interaction with physical health in common,” the authors wrote in Acta Psychiatrica Scandinavica.

Between 15% and 80% of older adults will experience polypharmacy, while its presence is associated with poor outcomes in this population, including falls, adverse drug reactions, cognitive problems, and sometimes mortality, the researchers explained.

“Although depression is a major contributor to the global burden of diseases and, like polypharmacy, is highly prevalent in later life, the relationship between polypharmacy and late-life depression is poorly understood,” they added.

To determine if an association between polypharmacy and late-life depression exists and to elucidate whether polypharmacy affects the course of late-life depression, the investigators assessed data from the Netherlands Study of Depression in Older Persons (NESDO).

A total of 375 patients with depression, aged 60 or older, were included in NESDO along with 130 nondepressed controls. Polypharmacy was defined in 2 ways: as the chronic simultaneous use of 5 or more medications daily and as number of drugs, resulting in a continuous variable.

Diagnoses of major depressive disorder and dysthymia were assessed in addition to severity, symptom dimensions, and subtypes of depressive symptoms. “Patients with depression were categorized as either having ‘normal’ depression, depression with atypical features, or depression with melancholic features,” the authors wrote.

In general, those with diagnosed depression tended to have a lower level of education, lower income, more chronic somatic diseases, and higher feelings of loneliness.

Analyses revealed:

  • Polypharmacy was more prevalent among patients with depression (46.9%) vs nondepressed controls (19.7%)
  • A lower level of education, lower cognitive functioning, and more chronic diseases were independently associated with polypharmacy
  • After adjustment, polypharmacy was associated with a higher level of motivational problems, anxiety, pain, and an earlier age of depression onset
  • A higher number of drugs was associated with a worse course of late-life depression (OR, 1.24; 95% CI, 1.03-1.49; P = .022)

“A higher number of prescribed drugs was associated with a more severe course of late-life depression, even after adjustment for known biopsychosocial determinants of polypharmacy, including age, sex, level of education, number of chronic somatic diseases, baseline depressive symptom severity, and psychotropic drug use,” the researchers said, a findings that suggests polypharmacy is an independent risk factor for chronic depression.

Forty-seven percent of patients with depression had polypharmacy compared with 1 in 5 healthy controls included in the study.

Several hypotheses may account for the association found, including the impact of a high number of chronic diseases on depression course and the possibility of drugs’ adverse effects, which can include depression.

Furthermore, “reverse causality cannot be excluded, as a protracted course of elevated depressive symptoms may be associated with an increased level of medical consumption,” the authors wrote.

The relatively small sample sizes included in the analysis marks a limitation to the study.

Overall, after adjusting for number of somatic diseases and excluding antidepressants, the researchers found those with late-life depression were more prone to polypharmacy.


Wiersema C, Voshaar RCO, van den Brink RHS, et al. Determinants and consequences of polypharmacy in patients with a depressive disorder in later life. Acta Psychiatr Scand. Published online April 18, 2022. doi:10.1111/acps.13435

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