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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: (Published 14 July 2015) Cite this as: BMJ 2015;351:h3517
  1. Ju-Young Shin, director1,
  2. Mi-Ju Park, senior researcher1,
  3. Shin Haeng Lee, researcher1,
  4. So-Hyun Choi, researcher1,
  5. Mi-Hee Kim, researcher1,
  6. Nam-Kyong Choi, research professor2,
  7. Joongyub Lee, research professor2,
  8. Byung-Joo Park, professor3
  1. 1Korea Institute of Drug Safety and Risk Management, 110-750 Seoul, Korea
  2. 2Medical Research Collaborating Center, Seoul National University College of Medicine and Seoul National University Hospital, 110-799 Seoul, Korea
  3. 3Department of Preventive Medicine, Seoul National University College of Medicine, 110-799 Seoul, Korea
  1. Correspondence to: B-J Park bjpark{at}
  • Accepted 16 June 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.

Design Retrospective nationwide propensity score matched cohort study.

Setting Korean nationwide health insurance database between 1 January 2009 and 31 December 2013.

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.


  • We thank staff at the Health Insurance Review and Assessment Service for their assistance with data acquisition and Jocelyn Graf from Proficia for English proofreading.

  • Contributors: All authors contributed to the study design and interpretation of data. S-HC and MJP had the main responsibility for statistical analysis, but all authors contributed. J-YS, MJP, and SHL wrote the manuscript, and all authors reviewed and commented on drafts and approved the final manuscript and the decision to submit for publication. J-YS is the guarantor.

  • Funding: This research received no specific grant from any funding agency in the public, commercial, or not for profit sector.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the institutional review board of the Korea Institute of Drug Safety and Risk Management, Seoul (study ID: KIDS-IRB-2013-007).

  • Data sharing: No additional data available.

  • Transparency declaration: The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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