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The use of antidepressants — particularly selective serotonin re-uptake inhibitors (SSRIs) — are associated with a “statistically substantial increased risk” of postural hypotension (PH) in older people during the first 28 days of use, according to the results of a study.
The study, published on 20 May 2025 in the British Journal of General Practice, identified a more than four-fold increased risk of the PH in patients aged over 60 years within the first four weeks of being prescribed SSRIs.
PH is defined as a reduction in systolic blood pressure (BP) of ≥20 mmHg or diastolic blood pressure of ≥10 mmHg within three minutes of standing up or on assuming a head-up position of at least 60 degrees during tilt-table testing.
The researchers analysed data from more than 41,000 patients aged over 60 years who were treated with antidepressants in UK primary care between 1 January 2000 and 31 December 2018, using routinely collected data from the IQVIA Medical Research Database (IMRD).
Prescriptions featured in the study included tricyclic and related antidepressant drugs, such as amitriptyline; SSRIs, such as sertraline; and other antidepressant drugs including agomelatine, duloxetine, flupentixol and mirtazapine.
The researchers examined the risk of PH during four exposure risk periods (90-days pre-prescription; day 1–28; 29–56; and ≥57) compared with periods outside these risk windows and found “a striking increased risk of PH with use of all antidepressants (over a four-fold increased risk with SSRIs) in the first 28 days of initiation”.
Among the 41,005 patients with incident PH during the study period, 8,899 people (22%) were prescribed SSRIs; 8,313 patients (20%) were prescribed a tricyclic antidepressant (TCA); and 4,656 patients (11%) were prescribed an ‘other antidepressant’.
The study authors observed “a consistent increased risk of PH in day 1–28 in all antidepressant exposure, which reduced thereafter”.
According to the study results, the risk of PH was highest with SSRIs (incidence rate ratio (IRR) 4.22, 95% confidence interval (CI) 3.76–4.74), followed by ‘other antidepressants’ (IRR 2.17, 95% CI 1.76–2.68) and then TCAs (IRR 2.12, 95% CI 1.79–2.50).
The results also showed that the risk of PH reduced from day 28 for all antidepressants.
The authors concluded: “Late-life depression is common, and often the decision to prescribe an antidepressant has carefully considered the balance between risk and benefit in the older patient.
“Findings from the presented study support safe prescribing of antidepressants where indicated, [and] prescribers may consider monitoring for PH in high-risk patients — for example, those at risk of falls or at risk of PH for other reasons, such as comorbid diabetes or Parkinson’s disease.”
Commenting on the study, Ian Maidment, professor of clinical pharmacy at Aston University, said: “This study builds on the evidence that antidepressants can cause PH, particularly in older people and when initially started.
“Pharmacy staff should be aware of this risk and possible consequences, including falls; critically they should counsel patients and family carers on the risks.
“From October 2025, the community pharmacy new medicines service will be expanded to include depression, providing further opportunity for person-centred care.”
