Antidepressants and NSAIDs Are a Dangerous Mix

Combining antidepressants and non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of intracranial hemorrhage within 30 days of administration, according to new research.

The researchers compared incidence of intracranial hemorrhage in more than 4 million individuals who took antidepressants for the first time with or without concurrent NSAID use between January 2010 and December 2013.

According to the study, the combined use of NSAIDs and antidepressants increased risk of intracranial hemorrhage, regardless of whether tricyclic antidepressants, selective serotonin reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors were used. It appeared that advanced age or the use of antithrombotic agents did not increase incidence of intracranial hemorrhage in patients on the combined therapy. Men, however, were at greater risk.

Serotonin reuptake inhibitors, which block platelet uptake, are often associated with abnormal bleeding. The authors said NSAIDs have the same inhibitory effect on platelet function. They also noted that serotonin reuptake inhibitors block the reuptake of norepinephrine, elevated levels of which has been linked to increased risk of intracranial hemorrhage.

The drugs alone have been not been associated with increased risk of intracranial hemorrhage, according to the researchers, but questions remain about bleeding risks when the drugs are used in combination.

“We thought that the additional effect of the drug-drug interaction might increase the risk of intracranial hemorrhage,” said study co-author Dr. Byung-Joo Park, a professor in the department of preventative medicine at Seoul National University College of Medicine.

Antidepressants are known to block platelet uptake, and use of these agents results in bleeding complications, said Dr. Park. “NSAIDs are also known to inhibit normal platelet function,” he added. “However, a previous population-based study did not find a significant association between combined use of each drug and intracranial hemorrhage.”

Dr. Park pointed out that more than 2 million individuals in the study had taken the drugs concurrently, which showed the findings could have a substantial impact on public health.

“The study provided new information for the criteria of drug-drug interaction, and I think it’s one of the essential roles of health-system pharmacist to check the drug utilization based on most recent evidence,” commented Dr. Park.

“NSAIDs and antidepressants are commonly used drugs worldwide,” he added, “so patients who are already taking antidepressants should be monitored for the risk of hemorrhage in case they’re in need of additional NSAIDs prescription.”

The study was published online in The BMJ.

—Dan Cook

Reference:

1. Shin JY, Park MJ, Lee SH, et al. Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study. BMJ. 2015 Jul 14.