An article appeared in the British Journal of Psychiatry some weeks ago, by Narinder Bansal and colleagues from Bristol University.
Having met Narinder I can tell readers she is a very impressive woman, with an impressive husband, Petros, who are both in one way or another working on population health. She had been working in cardiovascular medicine but switched to psychiatry and population health; he is developing health services in Africa.
Narinder’s article is fascinating in many respects. The main one is that it is very careful. There are lengthy discussions about methods, and the possible confounders that might complicate the obvious interpretations of the study.
We hear about the limitations – all the things that might have gone wrong. We hear very little about the extraordinary results. Extraordinary enough to make one wonder how the British Journal of Psychiatry ever agreed to publish it.
The message is keep taking your antidepressants and you are more likely to die early.
Many readers will probably guess that a message like this has to be camouflaged and smuggled into a paper in order to appear in an establishment journal. Many doctors still think a journal like the BJP would welcome something fascinating like this – not so. The key message needs a lot of camouflaging and in this case appears most clearly in the figures rather than the text.
Narinder and co-authors mention that the original trials done to get current antidepressants on the market were short-term, lasting 6 weeks mostly, whereas many of those on these drugs have been on them for 5 years or more. So there were no studies done to give us a sense as to what the outcomes might be if people stayed on these treatments long-term.
In fact, though, even in the short-term trials, more people died on treatment than on placebo. Died from suicide. And died from other causes also. Very few people know that. So it was a good move on Narinder’s part to say well we couldn’t have really known what was likely to happen.
But even if the results from the short-term early trials had not found the problem that was brushed under the carpet, there were good grounds to think that what Narinder found is exactly what might have been expected.
Short of a drug that very obviously saves lives in the short term, like Insulin or antibiotics, you have to expect that anything taken in the long term is going to shorten your life. Nicotine does. Alcohol does. And these are safe drugs – available over the counter because we figure people can manage the risks themselves. Antidepressants and other drugs are on prescription because we figure they are more dangerous than alcohol or nicotine – more likely to lead to a premature death if taken chronically.
This is not just an antidepressant issue. Many drug groups end up being Legacy Prescribed – to use Dee Mangin’s term. We get put on PPIs for gut acid, bisphosphonates for brittle bones and other drugs and just left on them. This has to be a reason, perhaps even the main reason ,why life expectancies particularly in the United States were falling even before COVID – see Shipwreck of the Singular.
Among the fascinating details in Narinder’s paper is that SSRIs in particular may even be somewhat hypoglycemic or good for diabetes and also not bad for hypertension.
This seems superficially at odds with the overall message that they increase rates of death from cardiovascular causes.
Pharmaceutical companies, however, initially thought the SSRIs might be useful anti-hypertensive and if they had been slightly more anti-hypertensive than they are they would never have become antidepressants. The idea back in the 1970s loosely was that actions on serotonin would vasodilate.
However Luisa Guerrini, currently funded by RxISK to look at the effects of SSRIs on the p63 transcription factor – see Holy Grail and Research Fund – has found that just like thalidomide, these drugs destabilize p63 and this downregulates the ACE2 (angiotensin converting enzyme) receptor.
This is important because ACE1 and ACE2 receptors are part of the Renin-Angiotensin-Aldosterone-System which is the main controller of blood pressure. And Serotonin interacts with ACE systems throughout the body – including in the brain. So we might expect SSRIs to have effects on blood pressure, mainly lowering it as ACE2 receptor blockers do.
Luisa has also found that metformin, the premier hypoglycemic medicine we have (a drug discovered in Dublin a century ago this year) also acts to destabilize ACE2 receptors. This may be the way SSRIs lower blood sugar. People taking these drugs have known about their effects on glucose for decades and 20 years ago many thought this might be part of the reason why we get hooked to them and find it difficult to stop.
Narinder’s finding of blood sugar effects has been recently reported by others – see SSRIs and Diabetes. It would be fascinating if Luisa Guerrini’s current RxISK funded research helps explain this.
So if the cardiovascular deaths on SSRIs are not caused by hypertension or diabetes, what are they caused by?
RxISK and DH.org have many posts about disturbances in cardiac rhythm leading to sudden cardiac death. See Tell-Tale Heart and Tell-Tale Heart 2 as well as the Reverse Dodo Effect and Jeannie’s Story.
We also know SSRIs increase the risk of bleeding into your uterus, gut and brain. Add some aspirin to this and you put yourself at real risk. This will not be a hypertensive stroke – it will be an hemorrhagic one.
All of the details in Narinder’s paper add up. She doesn’t make a point of saying this. She says we need more research to work out what is going on.
Hers is a paper that should give doctors pause for thought before prescribing and should get those of us on these medicines thinking it might be wiser to stop – except that is easier said than done. Many feel so uncomfortable when they try to stop that they end up thinking these pills are truly saving their lives.
The Queen died just as Narinder’s article came out and media was limited for the first few weeks. But a lot of coverage has happened since. None of it gives you any hint that it might not have been easy or straightforward to get this article published.
RxISK acknowledges that the experiences of those who have been harmed by medical treatments are the cornerstone on which it is built, and believes this should be the case for all of medicine.
See Black Robe, White Coat for more detail on this people acknowledgement