Concerns emerge over combining antidepressants with non-steroidal anti-inflammatory drugs (NSAIDs) as a study shows an increased risk of intracranial haemorrhage (ICH) in these patients.

Antidepressants and NSAIDs are both associated with gastrointestinal bleeding but not with ICH when used as monotherapy. Evidence now shows that the absolute risk of ICH in the first 30 days of combination treatment with an antidepressant and NSAID is 0.05 percent, with a hazard ratio (HR) of 1.6 vs treatment with an antidepressant alone (p<0.001). [BMJ 2015;351:h3517]

Subgroup analyses found no significant difference in ICH risk between the antidepressant drug classes for tricyclic antidepressants (HR, 1.7), selective serotonin reuptake inhibitors (HR, 1.4), and serotonin-norepinephrine reuptake inhibitors (HR, 0.4) vs all other drug classes. The risk of ICH, however, was greater in men (HR, 2.6) than women (HR, 1.2), but there was no association between ICH risk and patient comorbidities or other co-medications.

The retrospective analysis was performed using data from over 4 million Korean patients, taken from the Korean Health Insurance Review and Assessment Service database. All patients were treated with antidepressants between 2009 and 2013.

The study is the first population-based cohort study to highlight the risk of ICH associated with the combined use of antidepressants and NSAIDs. The potential risk of interaction posed by their concomitant use may be substantial, experts warn, especially with the increasing use of antidepressants and overuse of over-the-counter NSAIDs.

“The availability of over-the-counter analgesics is particularly important, as doctors often fail to consider the risks and potential interactions posed by non-prescribed drugs,” wrote Professor Stewart Mercer and colleagues of the University of Glasgow, Glasgow, UK and the University of Cambridge, Cambridge, UK in an accompanying editorial. [BMJ 2015;351:h3745]

“Most worryingly, conditions requiring NSAIDs and antidepressants commonly coexist; 65 percent of people with major depression also have chronic pain, with both morbidities sharing common psychological risk factors and neurobiological processes,” they wrote.

Vigilance in prescribing and assessment of individual patients’ risks and needs are recommended. According to Mercer and colleagues, knowing the patient and applying an empathic, person-centred approach to care may be “as important as having better guidelines and a better evidence base.”

Further research will be needed to address the risk of ICH with the individual treatments used alone, as well as the risks associated with long-term use of combination treatment.