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expert reaction to study looking at statins and serious mental illnesses

Research published in JAMA Psychiatry provides evidence that exposure to statins might help people with serious mental illness.

Dr Derek Tracy, Royal College of Psychiatrists, said:

“The often limited effectiveness of existing medication treatments for schizophrenia are well known, as are their side effects. These remarkable results suggest that an entirely new class of medication – at least new in terms of mental health – may offer benefits.

“The study is well designed, with very large numbers of participants. The authors recognise that what remains to be determined is how such drugs might be benefiting people with serious mental illness, or if there are other variables affecting the results, such as the ‘type’ of person on medications or engaging well with medical care.

“Given the burden of schizophrenia, these results pave the way for further testing of the impact of statins, ideally using a scientific randomised controlled test.”

Prof. Guy Goodwin, Professor of Psychiatry, University of Oxford, said:

“The use of big data to examine real world drug effects is a very exciting recent development. Quasi-experimental designs that control for the most obvious sources of error in such studies give them power and credibility. The finding that statins, calcium antagonists and biguanides may reduce self-harm and psychiatric hospitalisation by substantial amounts in patients with bipolar disorder and psychosis (severe mental illness) is practically important and theoretically very interesting. Serendipity has served psychiatry well in the past and it appears set to do so again. These finding incidentally underline the need to include physical illness as the key co-morbidity of severe mental illness.”

Dr James MacCabe, Clinical Reader in Psychosis Studies, King’s College London’s Institute of Psychiatry, Psychology & Neuroscience, said:

“The study used Swedish population databases to determine whether using three commonly prescribed types of medicine (statins (which lower cholesterol), calcium channel blockers (which lower blood pressure) and metformin (which lowers blood glucose)) had any effect on reducing psychiatric hospital admissions and self-harm in people with severe mental illness.

“These findings are very compelling. There is a misconception that randomised controlled trials are the only form of evidence that can be trusted, but they are of relatively short duration and small size. By studying large populations over a long time in this way, one can detect effects on rare events, such as hospital admissions, that would be missed by clinical trials. There are pitfalls to such studies but the authors have convincingly ruled these out. In particular, these effects seems specific to these three classes of drug and for psychiatric outcomes.

“These findings will need to be independently replicated before any recommendations should be made to change practice, but the findings strongly suggest a potential role for repurposing these drugs to improve mental health outcomes. Given that people with severe mental illness have high rates of cardiovascular disease, these drugs could have a double effect: improving both mental and physical health.”

Prof Allan Young, Professor of Mood Disorders, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, said:

“This fascinating study suggests that statins might benefit the mental health of people with serious mental health problems.  Although this finding will need to be tested further in clinical trials it raises the prospect of “repurposing” these medicines as treatments for mental ill-health.  This seems credible for a number of reasons:  these drugs probably act on the brain as well as the body; there is already evidence that statins may confers extra benefits to antidepressants and, lastly, there is a venerable history of medicines for “physical” health disorders (including anaesthetics, TB drugs and anticonvulsants) being successfully repurposed to treat psychiatric disorders.”

Professor Daniel J. Smith, Professor of Psychiatry, University of Glasgow, said:

“This very large study used routinely-collected ‘real world’ clinical data from Sweden. It adds to a growing body of evidence that medications like statins may potentially be useful in the treatment of severe mental illness, when used alongside treatments such as antipsychotics and mood stabilisers. These findings are interesting and should simulate further work in this area but, as the authors acknowledge, it is difficult to establish conclusively that the ‘non-psychiatric’ medications were directly protective against self-harm and hospitalisation within the patient groups studied.

“Given the enormous complexity and expense associated with developing new medications for psychiatric disorders, studies of this nature that make use of routine data are very welcome. Also, people with severe mental illness are at higher risk of cardiovascular disease, so it is possible that low cost and well-tolerated medications like statins could be reasonable additional treatment options to improve both physical and mental health outcomes.”

Professor Naveed Sattar, Professor of Metabolic Medicine, University of Glasgow, said:

“I am somewhat sceptical of the headline findings here – intuitively, people are more like to take any drugs when they are in better mental health and less likely when they are not – so reverse causality (whereby periods of poor mental health lead to lower drug exposure for statins, metformin and blood pressure drugs) could be a likely explanation rather than any real effects of these drugs on mental health. Even though the authors claim they overcame this bias, I am not sure they did so fully.  Also, their explanations for how these drugs may improve mental health are highly speculative. So I would be strongly cautious with these findings and would only change my mind if effects are proven to be robust in a randomised trial setting.”

‘Association of Hydroxylmethyl Glutaryl Coenzyme A Reductase Inhibitors, L-Type Calcium Channel Antagonists, and Biguanides With Rates of Psychiatric Hospitalization and Self-Harm in Individuals With Serious Mental Illness’ by Hayes et al. was published in JAMA Psychiatry at 16:00 UK time on Wednesday 9th January 2019.

All our previous output on this subject can be seen at this weblink:

Declared interests

Professor Daniel J. Smith: “No conflict of interest.”

Professor Naveed Sattar: “No COI”

Dr James MacCabe: “No Cis”

Professor Guy Goodwin: “I have advised and do advise pharmaceutical companies on the development of new drugs for severe mental illness, but not these drugs which are now cheaply available in generic formulations.”

None others received.

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