SSRI Use Increases Risk of Post-Stroke Mortality in Patients with Diabetes

An analysis of population-based medical databases has found that strokes are more likely to prove fatal in diabetic patients who use selective serotonin reuptake inhibitors (SSRIs) than in diabetic patients who do not.

Investigators used government records to identify all first-time, stroke-related hospitalizations in Denmark between 2004 and 2012 and found that 12,620 of those patients were diabetics who died within 30 days of hospitalization. They then looked at redeemed prescriptions of SSRIs and categorized all diabetic stroke victims (both those who lived and those who died) as current users, former users or non-users of such antidepressant medications. Finally, the investigators used Cox regression to calculate both 30-day mortality rates and mortality rate ratios (MMRs) while controlling for potential confounders.

The overall 30-day stroke mortality rate was 15.8% for patients who had never used SSRIs (10.4% for patients who suffered ischemic stroke, 41.8% for those who suffered intracerebral hemorrhage and 27.3% for those who suffered subarachnoid hemorrhage). Among patients who used SSRIs, however, the 30-day stroke mortality rate was 23.3% (17.1% for ischemic stroke, 50.7% for intracerebral hemorrhage and 28.6% for subarachnoid hemorrhage).

After all adjustments, the investigators calculated that the MRR for stroke-related mortality of diabetic SSRI users compared to diabetic SSRI non-users was 1.3 (95% confidence interval [CI], 1.1 to 1.5).

Patients who had just started using SSRIs faced an even higher risk of death than patients who had been using the drugs for longer periods of time. The MMR for new SSRI users compared to non-users was 1.5 (95% CI, 1.2 to 1.8).

“Overall stroke mortality was driven by increased mortality due to ischemic 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,” the study authors wrote in the Journal of Internal Medicine. “In patients with diabetes, preadmission SSRI use was associated with increased mortality following ischemic stroke, compared with nonuse.”

Even small elevations in risk can lead to big elevations in mortality because of the numbers involved. According to the National Stroke Association, nearly 26 million Americans have diabetes, and diabetics are 2 to 4 times as likely to have a stroke than people who do not have diabetes. (The American Diabetes Association believes the risk to be slightly lower. Its literature says that diabetics are about 50% more likely to have a stroke than people who don’t have diabetes. A research review that appeared in Diabetes Care, however, put the age-adjusted stroke risk for diabetics relative to non-diabetics at 2.9.)

Diabetics are also more likely than members of the general public to use antidepressants, in part because antidepressant usage seems to spur weight gain and incident diabetes and in part because people with diabetes are more likely than others to be depressed. A 2010 article that appeared in Diabetes Care, analyzed data from 151,347 working-aged people and found the 5-year total rate of incident diabetes was between 1.7% and 2.3% (depending on dosage) for those who took antidepressants and 1.1% for similar (and similarly depressed) controls. A 2001 meta-analysis that also appeared in Diabetes Care, found that diabetic group members across many studies were typically about twice as likely to suffer from depression as control group members (OR = 2.0, 95% CI 1.8—2.2).