The study evaluated data from a total of 530,416 adults identified across 375 US hospitals, who underwent major surgery between the period 2006 and 2008. Perioperative use of SSRIs was noted, and the primary outcomes measured were in-hospital mortality, length of stay, readmission at 30 days, bleeding events, transfusions, and incidence of ventricular arrhythmias.
The researchers reported that patients receiving SSRIs were more likely to have obesity, chronic pulmonary disease, or hypothyroidism, and more likely to have depression (41.0% vs. 6.2%, P < 0.001). However, after adjusting for these factors, compared with those who did not receive SSRIs, patients who received SSRIs had higher overall mortality (adjusted odds ratio, 1.20 [95% CI, 1.07-1.36]; number needed to harm (NNH), 839), higher 30-day readmission (1.22 [1.18-1.26]; NNH 75), and higher odds for bleeding (1.09 [1.04-1.15]; NNH 424).
A number of limitations to the study were highlighted, including the observational nature of the study, and a requirement to determine whether patient factors or SSRIs themselves are responsible for these elevated risks – which would require a prospective study. Additionally, this study was not powered to address whether temporary discontinuation of SSRIs would result in favourable outcomes, or whether certain patients are at particularly higher risk.
An editorial which comments on this study states that even if a causal relationship exists, the number needed to harm is quite large, and thus the attendant increase in absolute risk for the average patient would be very small. Conversely, the cessation of SSRI therapy before surgery may precipitate a discontinuation syndrome, worsen depression, and increase sensitivity to postoperative pain. Physicians should therefore continue to initiate SSRI therapy only when clinically indicated, and be aware of potential bleeding risks in patients receiving SSRIs in the perioperative setting. Overall, however, the evidence base has evolved sufficiently to confirm that patients should not routinely have their SSRI therapy tapered or discontinued before surgery, unless there is a clinical need to do so.
The Maudsley Prescribing Guidelines in Psychiatry state that SSRI use is probably safe during surgery, but should be avoided with other serotonergic drugs. The guideline also notes that cessation of treatment with SSRIs may cause discontinuation syndrome, whilst continued use may increase bleeding times, and interactions with other medicines used during surgery should be accounted for.