Association between use of B-blockers and depression not causal but due to protopathic bias: Study

Depression is a commonly cited adverse effect of β-blockers but the evidence for a causal relationship is limited.

A group of researchers conducted a study to explore whether β-blockers are associated with an increased risk of new-onset depression.

The researchers conducted a case-control study using the UK population-based Clinical Practice Research Datalink (CPRD) GOLD. They identified patients aged 18−80 years with an incident depression diagnosis between 2000 and 2016, matched controls, and estimated the risk (odds ratio [OR]) of depression in association with the use of β-blockers. They also conducted analyses of exposure, categorised by number and timing of prescriptions and by indication for β-blocker use.

The Results of the study are:

The study encompassed 118,705 patients with incident depression and the same number of matched controls. The odds of developing depression were increased for current short-term use of any β-blocker (adjusted OR [aOR] 1.91, 95% confidence interval [CI] 1.72−2.12), whereas current long-term use was not associated with the risk of depression compared with never use. The elevated risk of depression among short-term users was mostly confined to propranolol users with a neuropsychiatric disorder (aOR 6.33, 95% CI 5.16–7.76), while propranolol users with a cardiovascular indication were only at marginally increased risk of depression (aOR 1.44, 95% CI 1.14–1.82).

Thus, the researchers concluded that the population-based observational study suggests that the association between the use of β-blockers and depression may not be causal but rather a result of protopathic bias. Propranolol is often prescribed to treat neuropsychiatric symptoms, suggesting that the onset of depression may be related to the underlying indication rather than to an effect of a β-blocker therapy. The reported high risk of new-onset of depression after use of propranolol may be explained by protopathic bias and not by a pharmacological effect of propranolol. The findings suggest that the reported association between the use of β-blockers and depression may not be causal but rather a result of protopathic bias.

Reference:

Bornand D, Reinau D, Jick SS, Meier CR. β‑blockers and the risk of depression: A matched case-control study. Drug Safety. Published online January 19, 2022. https://doi.org/10.1007/s40264-021-01140-5.