Intended for healthcare professionals

Rapid response to:


Risk of intracranial haemorrhage linked to co-treatment with antidepressants and NSAIDs

BMJ 2015; 351 doi: (Published 14 July 2015) Cite this as: BMJ 2015;351:h3745

Rapid Response:

Re: Risk of intracranial haemorrhage linked to co-treatment with antidepressants and NSAIDs

Mercer et al. refer to the new-found risk of Intracranial haemorrhage in Korea, in the first 30 days of combination NSAID and antidepressant. “The implications of these new findings for general practitioners and primary care teams need to be understood. Guidelines are generally poor at informing therapeutic decisions in patients with multimorbidity, in whom polypharmacy is ubiquitous. This makes evidence based decision making very difficult, as useful information such as number needed to treat and number needed to harm is often lacking”.

I disagree. General practice prescribing is now almost entirely computer-based, and interacts with the full patient record. Every attempt to prescribe an NSAID or an antidepressant bombards the GP with myriad warnings of interactions, cautions and contraindications. GPs generally raise the threshold at which the warnings are triggered, in order to prescribe at all !

So can we quantify the NNT ? According to Shin’s paper, the risk was only reached statistical significance in men They state that “comorbidities and comedications did not seem to increase the risk.” The online paper refers to “comorbidities that may influence the risk of intracranial haemorrhage, which included diabetes, chronic obstructive pulmonary disease, hypertension, osteoarthritis, rheumatoid arthritis, osteoporosis, alcohol related disorder, ischaemic heart disease, chronic kidney disease, peptic ulcer, dementia, non-alcoholic liver disease, schizophrenia, neoplasm, HIV infection, transplantation, atrial fibrillation, heart failure, disease of arteries, and disease of veins. Low dose acetylsalicylic acid, steroids, warfarin, heparin, platelet aggregation inhibitors, antithrombotic enzymes, direct thrombin inhibitors, direct factor Xa inhibitors, and other antithrombotic agents.

Shin’s paper shows the background risk for any gender taking Antidpressants only, was 1.6 per 1000 patient years. Unfortunately the table does not further subdivided by gender, but combining Antidepressants + NSAIDs gives an overall additional risk of 4.1 haemorrhages per 1000 patient years, which equates to about 0.33 per 1000 patient months. Thus UK general practitioners should be informed that if the Korean findings can be extrapolated then

“among 3000 MEN initiating an NSAID whilst on an antidepressant ( or vice versa) one will suffer an avoidable additional intracranial haemorrhage in the first 30 days”

Competing interests: No competing interests

17 July 2015
L Sam Lewis
retired GP
Surgery, Newport, Pembrokeshire SA42 0TJ