Research
Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study
BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h3517 (Published 14 July 2015)

Objective
To define the risk of intracranial haemorrhage among patients treated with antidepressants and non-steroid anti-inflammatory drugs (NSAIDs), compared with the risk among those treated with antidepressants without NSAIDs.

Participants
Patients who began receiving antidepressants for the first time (index date) without a history of having received a prescription for antidepressants during the preceding year. Patients who had been diagnosed as having cerebrovascular diseases within a year before the index date were excluded.

Main outcome measure
Time to first hospital admission with intracranial haemorrhage within 30 days after drug use. Matched Cox regression models were used to compare the risk of intracranial haemorrhage among patients who were treated with antidepressants with and without NSAIDs, after propensity score matching with a 1:1 ratio.

Results
After propensity score estimation and matching in a 1:1 ratio, the cohort used in the analysis included 4?145?226 people.
The 30 day risk of intracranial haemorrhage during the entire study period was higher for combined use of antidepressants and NSAIDs than for use of antidepressants without NSAIDs (hazard ratio 1.6, 95% confidence interval 1.32 to 1.85).
No statistically meaningful differences were found in risk of intracranial haemorrhage between the antidepressant drug classes.

Conclusions
Combined use of antidepressants and NSAIDs was associated with an increased risk of intracranial haemorrhage within 30 days of initial combination.

DISCUSSION.
Depression produces the greatest decrement in health of all common chronic conditions, and depression in older people is an important public health problem.
Antidepressants can help depressive patients effectively, but concern exists that antidepressants may interact unfavourably with non-steroidal anti-inflammatory drugs (NSAIDs).

Antidepressants, especially selective serotonin reuptake inhibitors, and NSAIDs are each thought to increase the risk of abnormal bleeding.According to the results of a meta-analysis in 2008, the odds ratio of upper gastrointestinal haemorrhage was 2.36 (95% confidence interval 1.44 to 3.85) for selective serotonin reuptake inhibitors alone and 6.33 (3.40 to 11.82) with concomitant NSAIDs, although controversy exists about whether the risk of gastrointestinal bleeding increases when they are prescribed together, compared with their use alone.

Unlike for gastrointestinal bleeding, neither selective serotonin reuptake inhibitors nor NSAIDs alone have been found to be associated with an increased risk of intracranial haemorrhage.
However, little is known about the risk of intracranial haemorrhage associated with the combined use of antidepressants and NSAIDs.

What is already known on this topic
Antidepressants and non-steroidal anti-inflammatory drugs (NSAIDs) are generally believed to each increase the risk of abnormal bleeding
However, very little is known about the risk of intracranial haemorrhage associated with the combined use of antidepressants and NSAIDs
What this study adds
Combined use of antidepressants and NSAIDs was associated with an increased risk of intracranial haemorrhage within 30 days of initial combination.

G Mohan