Horace Walpole, 1741, Rosalba Carriera (1673-1757)
Horace Walpole, an asexual and effete afterthought son of Prime Minister Robert Walpole, neo-Gothic architect, obsessive hoarder, abundant writer, a politician with more than an iota of intellect, had coined the word ‘serendipity’ on 28 January 1754 to describe ‘the discovery through change by a theoretically prepared mind of valid findings which were not sought for,’ otherwise known as ‘active luck.’
Walpole had remembered the ancient Persian fairy tale of the super deductive powers of ‘The Three Princes of Serendip’ – Serendip, Ceylon, Sri Lanka – which could also have spawned the inspiration for Arthur Conan Doyle’s Sherlock Holmes.
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Serendipity can be applied to any number of modern happy finds from the Post-It note to penicillin, from Velcro to Valium – or indeed, Viagra.
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Today, one of our neediest concerns is dementia, the effective treatment of which has yet to be concocted. The dread disease is accelerating. ‘In England and Wales, the number of people living with dementia has been predicted to increase by 57% from 0.77 million in 2016 to 1.2 million in 2040,’ The Lancet Public Health, 2 January 2024. ‘One in eleven people over the age of 65 has dementia in the UK,’ NHS, 20 July 2023.
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Founded in 2007, UK Biobank gathers a wide range of detailed biological and medical data garnered from an ongoing study of half a million healthy volunteers between ages of 40 and 60 years living in the UK.
The sample consists of equal numbers of males and females reflecting the UK population of 94.6% white people and 5.4% mixed race and people of colour. (PMID 28641372)
A recent observation by UK Biobank has been the association of the use of PDE5 inhibitors, the ‘Viagras,’ with significantly less incidence of dementia.
British Simon Campbell of Pfizer was knighted in the 2015 New Year Honours for services to chemistry. He had accelerated sildenafil from a failed trial of a treatment of high blood pressure to Viagra The Invigorator – a majorly serendipitous success, it’s annual sales taking US $1.934 billion in 2008.
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In September 2023, St George’s University (previously St George’s Hospital Medical School) and four US academic institutions published ‘PDE5 inhibitor Drugs for Use in Dementia?’ (PMID 37766832)
The highlights of this paper are –
- * Potent phosphodiesterase – 5 (PDE5) inhibitors are in clinical use as vasodilators (dilators of arteries)
- * In animals PDE5 inhibitors enhance synaptic function and cognitive ability (transmission of nerve impulses and processing of information)
- * In humans the PDE5 inhibitor sildenafil is associated with reduced risk of Alzheimer’s disease
- * Licensed PDE5 inhibitors have potential for repurposing in dementia
- * Prospective clinical trials of PDE5 inhibitors are warranted.
It is estimated that it takes 7 years or more to complete all main phases of a randomised controlled trial (RCT). Trialling an established medicine for repurposing is said to be somewhat shorter. The cost can be prohibitive, the median being £15 million.
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There is no way we can wait that long. The use of a previously licensed drug by a qualified medical practitioner in a repurposed role is fully allowed, being described as ‘off-label use.’
The doctor is simply obliged to ask for ‘informed consent’ from the patient, having fully explained the pro’s and con’s associated with the medicine in question.
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Having taken inferences from the strong but incomplete academic narrative, we feel justified in suggesting to our patients of age 60 or more that they seriously consider taking a small daily dose of the PDE5 inhibitor tadalafil as a safe preventative measure against dementia.
Our reasoning is as follows –
- * Cialis tadalafil was licensed for use as a treatment for erectile dysfunction in 2003.
- * Tadalafil has been licensed for use in “overactive bladder syndrome” (OBS).
- * Tadalafil remains effective for 36 hours (sildenafil for 4 to 5 hours) and is taken daily in small doses to maintain its effectiveness.
- * In the UK, generic tadalafil became available in 2017.
- * Generic tadalafil is significantly cheaper than proprietary Cialis.
- * The estimated usage of tadalafil in the US in 2022 was 709,112 patients.
- * Common side effects can include headache, indigestion, acid reflux, back pain, muscle pain, flushing, stuffy nose, all due to vasodilation.
- * No significant side effects are likely at the small daily dosage of 2.5 to 5mg, but patients with serious heart or liver complaints or have suffered recent heart attack or stroke are advised not to take tadalafil.
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Tadalafil has also been shown to reduce the risk of major adverse cardiovascular events and all-cause death in men with erectile dysfunction. The overall mortality rate was 44% lower in men exposed to tadalafil (n=8156). (PMID 38377018).
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We see no reason to withhold the use of tadalafil in the preventative treatment of our patients.
- – Richard Petty
