statins, low cholesterol make some people crazy

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"The medications that change who we are" by By Zaria Gorvett, BBC Future,
8th January 2020

The article discusses effects of drugs such as statins, paracetamol, L-dopa or antihistamines on personality disorder and character changes. Particulary interesting are statins side effects since these type of drugs are routinely prescribed with the intention of continous usage.

Quote:

“Patient Five” was in his late 50s when a trip to the doctors changed his life.

He had diabetes, and he had signed up for a study to see if taking a “statin” – a kind of cholesterol-lowering drug – might help. So far, so normal.

But soon after he began the treatment, his wife began to notice a sinister transformation. A previously reasonable man, he became explosively angry and – out of nowhere – developed a tendency for road rage. During one memorable episode, he warned his family to keep away, lest he put them in hospital.

Out of fear of what might happen, Patient Five stopped driving. Even as a passenger, his outbursts often forced his wife to abandon their journeys and turn back. Afterwards, she’d leave him alone to watch TV and calm down. She became increasingly fearful for her own safety.

Then one day, Patient Five had an epiphany. “He was like, ‘Wow, it really seems that these problems started when I enrolled in this study’,” says Beatrice Golomb, who leads a research group at the University of California, San Diego.

... Over the years, Golomb has collected reports from patients across the United States – tales of broken marriages, destroyed careers, and a surprising number of men who have come unnervingly close to murdering their wives. In almost every case, the symptoms began when they started taking statins, then promptly returned to normal when they stopped; one man repeated this cycle five times before he realised what was going on.

Golomb first suspected a connection between statins and personality changes nearly two decades ago, after a series of mysterious discoveries, such as that people with lower cholesterol levels are more likely to die violent deaths. Then one day, she was chatting to a cholesterol expert about the potential link in the hallway at her work, when he brushed it off as obviously nonsense. “And I said ‘how do we know that?’,” she says.

Filled with fresh determination, Golomb scoured the scientific and medical literature for clues. “There was shockingly more evidence than I had imagined,” she says. For one thing, she uncovered findings that if you put primates on a low-cholesterol diet, they become more aggressive.

Golomb remains convinced that lower cholesterol can cause behavioural changes in both men and women
There was even a potential mechanism: lowering the animals’ cholesterol seemed to affect their levels of serotonin, an important brain chemical thought to be involved in regulating mood and social behaviour in animals. Even fruit flies start fighting if you mess up their serotonin levels, but it also has some unpleasant effects in people – studies have linked it to violence, impulsivity, suicide and murder.

If statins were affecting people’s brains, this was likely to be a direct consequence of their ability to lower cholesterol.

Since then, more direct evidence has emerged. Several studies have supported a potential link between irritability and statins, including a randomised controlled trial – the gold-standard of scientific research – that Golomb led, involving more than 1,000 people. It found that the drug increased aggression in post-menopausal women though, oddly, not in men.

In 2018, a study uncovered the same effect in fish. Giving statins to Nile tilapia made them more confrontational and – crucially – altered the levels of serotonin in their brains. This suggests that the mechanism that links cholesterol and violence may have been around for millions of years.

Golomb remains convinced that lower cholesterol, and, by extension, statins, can cause behavioural changes in both men and women, though the strength of the effect varies drastically from person to person. “There are lines of evidence converging,” she says, citing a study she conducted in Sweden, which involved comparing a database of the cholesterol levels of 250,000 people with local crime records. “Even adjusting for confounding factors, it was still the case that people with lower cholesterol at baseline were significantly more likely to be arrested for violent crimes.”.

Reference:

"Cholesterol and violence: is there a connection?", by
Golomb BA., Ann Intern Med. 1998 Mar 15;128(6):478-87.