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expert reaction to study looking at ACE inhibitor blood pressure drugs, angiotensin receptor blockers (ARBs) blood pressure drugs, and risk of suicide

Research, published in JAMA Network Open, reports on the association between some blood pressure medications and risk of suicide. 

 

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“This is a carefully conducted study, and as the authors say, the results should be regarded as preliminary.  This is in spite of other studies that suggest this could be a causal effect, the previous study [ref 13 Callreus et al] of this question did show an increase in risk of suicide for ARBs, but it was based on only 5 cases and there was considerable uncertainty in the estimates for the drugs that were compared.

“The paper itself suggests a number of factors that seem to be more strongly associated with suicide (including previous self-harm, alcohol abuse, anxiety or sleep disorders, psychoses, agitation, and related disorders, affective disorder, other mental health conditions, and even kidney and liver disease), and those with these risk factors, especially multiple ones, should be monitored closely since they may be markers for risk of suicide.  Any additional effect of an anti-hypertensive drug is likely to be relatively small.  It is important to know the distribution of these risks factors between the exposed and unexposed, as it could be that a small numbers of cases exposed to ARBs drive the overall findings.  It’s possible the supplemental information has this, but it isn’t available to me.

“The authors do not seem to discuss the absolute risks, and the data from this case-control study itself are not able to estimate the absolute risks directly.  However, the data available to them could do this, and it falls short of good and responsible risk communication to fail to bring into the discussion some estimate of absolute risk.  Suicide may not be that common in this age group, and so the absolute risk (not given by the authors) may be quite low.  Patients should not change their treatment based on these findings.

“There is an obvious misprint in the results: they say “antipsychotics (11.7%vs 31.%; standardized difference, 0.34)”, but it is a misprint – it should be 11.7% vs 3.1%.  It doesn’t affect the interpretation.”

 

Prof Sir Munir Pirmohamed, David Weatherall Chair of Medicine and NHS Chair of Pharmacogenetics, and Director of the MRC Centre for Drug Safety Science and Wolfson Centre for Personalised Medicine, University of Liverpool, said:

“The authors have shown that angiotensin receptor blockers, drugs widely used for the treatment of hypertension and other cardiovascular disorders, may be associated with a higher risk of suicide, compared with angiotensin converting enzyme inhibitors, which are also used for the treatment of hypertension.  The study was undertaken using a Canadian claims database.

“Their findings which show an association (but are not necessarily causative) are interesting, but have to be treated with caution.  As the authors themselves point out, there are many limitations to their approach.  A critical issue is the inability to control for all confounding factors.  There is also no clear mechanistic explanation for the association and the authors were unable to look at individual angiotensin receptor blockers, and instead have analysed them as a single class of drugs.  If correct, then this would be an important adverse reaction given the widespread use of these drugs – however, much more work needs to be undertaken, a critical aspect of which will be to replicate the findings in other datasets.”

 

‘Association Between Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, and Suicide’ by Muhammad Mamdani et al. was published in JAMA Network Open at 16:00 UK time on Wednesday 16 October 2019. 

DOI: 10.1001/jamanetworkopen.2019.13304

 

Declared interests

Prof Stephen Evans: “The only conflict of interest I have is that I currently take an ARB and have taken an ACEI.”

Prof Sir Munir Pirmohamed: “I do not have any conflicts of interest.”

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