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SSRi Use Increases Stroke Mortality Risk in Diabetes

Current use of selective serotonin reuptake inhibitors was associated with a 23.3% risk of 30-day stroke mortality among diabetes patients hospitalized for stroke, compared with a 15.8% risk among those who didn’t take the drugs.

For patients with diabetes, preadmission selective serotonin reuptake inhibitor (SSRI) use is associated with increased risk of stroke mortality, according to a study published online May 3 in the Journal of Internal Medicine.

Danish researchers used a cohort of 12,620 patients and found that the 30-day stroke mortality risk among current SSRI users was 50.7% for intracerebral hemorrhage, 28.6% for subarachnoid hemorrhage and 17.1% for ischemic stroke.

Morten Würtz, M.D., Ph.D., from Aarhus University Hospital in Denmark, examined the correlation between preadmission SSRI use and mortality in patients with diabetes who were hospitalized due to stroke. Patients with diabetes with first-time stroke-related hospitalizations and subsequent mortality were identified from population-based medical databases (12,620 patients). SSRI use was categorized as current, former, or nonuse based on redeemed prescriptions.

Patients with diabetes have an increased risk of stroke with a poor prognosis. Moreover, diabetes patients are at an increased risk of depression and therefore likely to use selective serotonin reuptake inhibitors (SSRIs).  They examined whether pre admission SSRI use was associated with increased mortality in diabetic patients hospitalized due to stroke.

Population-based medical databases were used to identify all first-time stroke-related hospitalizations and subsequent mortality in diabetes patients between 2004 and 2012 (n = 12 620). Based on redeemed prescriptions, SSRI use was categorized as current (new or long term), former or nonuse, and absolute 30-day mortality and mortality rate ratios (MRRs) were computed using Cox regression controlling for confounding factors.

The results showed that amongst SSRI nonusers, 30-day stroke mortality was 15.8% (10.4% for ischemic stroke, 41.8% for intracerebral hemorrhage and 27.3% for subarachnoid hemorrhage). Amongst current SSRI users, 30-day stroke mortality was 23.3% (17.1% for ischemic stroke, 50.7% for intracerebral hemorrhage and 28.6% for subarachnoid hemorrhage). SSRI use was associated with increased 30-day stroke mortality compared with nonuse [adjusted MRR 1.3, 95% confidence interval (CI) 1.1–1.5], with the highest risk observed amongst new users (MRR 1.5, 95% CI 1.2–1.8).

Overall stroke mortality was driven by increased mortality due to ischaemic stroke, with adjusted MRRs of 1.3 (95% CI 1.1–1.7) for current users and 1.7 (95% CI 1.2–2.4) for new users. Propensity score-matched results were similar and robust across subgroups.

Selective serotonin reuptake inhibitors (SSRIs) are used commonly to treat post-stroke depression. They are also being evaluated in clinical trials for their effectiveness in facilitating functional recovery after stroke.

Furthermore, a meta-analysis of 16 observational studies involving 506,411 participants reported that SSRIs are also associated with an increased risk of intracerebral hemorrhage (ICH; adjusted risk ratio, 1.42; 95% CI, 1.23–1.64; I2=29%).6 Given an estimated global incidence of ICH of 24.6 per 100 000 person-years, these data suggested that SSRIs may realize 1 additional ICH per 10 000 persons (0.01%) treated for 1 year.

“In patients with diabetes, preadmission SSRI use was associated with increased mortality following ischemic stroke, compared with nonuse,” the authors write.

The results showed that amongst SSRI nonusers, 30-day stroke mortality was 15.8% (10.4% for ischemic stroke, 41.8% for intracerebral hemorrhage and 27.3% for subarachnoid hemorrhage).

Population-based medical databases were used to identify all first-time stroke-related hospitalizations and subsequent mortality in diabetes patients in Denmark between 2004 and 2012 (n = 12 620). Based on redeemed prescriptions, SSRI use was categorized as current (new or long term), former or nonuse, and absolute 30-day mortality and mortality rate ratios (MRRs) were computed using Cox regression controlling for confounding factors.

Practice Pearls:

  • In patients with diabetes, preadmission SSRI use was associated with increased mortality following ischemic stroke, compared with nonuse.
  • SSRIs are also associated with an increased risk of intracerebral hemorrhage.
  • Patients with diabetes have an increased risk of stroke with a poor prognosis.

Preadmission use of selective serotonin reuptake inhibitors and short-term mortality in diabetic patients hospitalized due to stroke. http://onlinelibrary.wiley.com/doi/10.1111/joim.12512/full, Journal of Internal Medicine. May 2016.