The medications that change who we are

The medications that change who we are – BBC FutureBy Zaria Gorvett – Jan 2020

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.

We’re all familiar with the mind-bending properties of psychedelic drugs – but it turns out ordinary medications can be just as potent.  

From paracetamol (known as acetaminophen in the US) to antihistamines, statins, asthma medications and antidepressants, there’s emerging evidence that they can make us impulsive, angry, or restless, diminish our empathy for strangers, and even manipulate fundamental aspects of our personalities, such as how neurotic we are.

In most people, these changes are extremely subtle. But in some they can also be dramatic.

The list of potential culprits includes some of the most widely consumed drugs on the planet, meaning that even if the effects are small at an individual level, they could be shaping the personalities of millions of people. 

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.

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.

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.

This is a great example of how, in living bodies, tampering with one molecule or biochemical process can cause changes even in completely unrelated tissues or processes.

It’s also a classic example of honestly unintended consequences, unintended due to a lack of knowledge, which is fixable, not “unintended” used as an excuse for causing harm, which is a deliberate and highly defended falsehood resistant to any change… (see Were Consequences of CDC Guideline Really Unintended?)

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.

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.

But Golomb’s most unsettling discovery isn’t so much the impact that ordinary drugs can have on who we are – it’s the lack of interest in uncovering it.

for a long time, research into the side-effects of statins was all focused on the muscles and liver, because any problems in these organs can be detected using standard blood tests.

Once again, research doesn’t follow real questions but focuses only on “measurables”, studies that can generate numerical results instead of more complicated and significant.

I’m noticing that research often focuses on almost irrelevant measures (milligrams of opioids prescribed) rather than critical information that can’t be pinned down to a number (patients’ pain outcomes).

This is something that Dominik Mischkowski, a pain researcher from Ohio University, has also noticed.

We know a lot about the physiological effects of these drugs – whether they have physical side effects or not, you know. But we don’t understand how they influence human behaviour.

Mischkowski wondered whether painkillers might be making it harder to experience empathy. Earlier this year, together with colleagues from Ohio University and Ohio State University, he recruited some students and spilt them into two groups. One received a standard 1,000mg dose of paracetamol, while the other was given a placebo.

The results revealed that paracetamol significantly reduces our ability to feel positive empathy – a result with implications for how the drug is shaping the social relationships of millions of people every day. Though the experiment didn’t look at negative empathy – where we experience and relate to other people’s pain – Mischkowski suspects that this would also be more difficult to summon after taking the drug.

Empathy doesn’t just determine if you’re a “nice” person, or if you cry while you’re watching sad movies. The emotion comes with many practical benefits, including

– some scientists have even suggested that it’s responsible for the triumph of our species. In fact, a quick glance at its many benefits reveals that casually lowering a person’s ability to empathise is no trivial matter. 

Technically, paracetamol isn’t changing our personalities, because the effects only last a few hours and few of us take it continuously. But Mischkowski stresses that we do need to be informed about the ways it affects us, so that we can use our common sense.

Yet this assumes that we all have common sense, an assumption that’s been proven wrong many times in many ways by many people in many situations.

One reason medications can have such psychological clout is that the body isn’t just a bag of separate organs, awash with chemicals with well-defined roles – instead, it’s a network, in which many different processes are linked.

For example, scientists have known for a while that the medications used to treat asthma are sometimes associated with behavioural changes, such as an increase in hyperactivity and the development of ADHD symptoms.

Then, more recently, research uncovered a mysterious connection between the two disorders themselves; having one increases the risk of having the other by 45-53%.

No one knows why, but one idea is that asthma medications bring on ADHD symptoms by altering levels or serotonin or inflammatory chemicals, which are thought to be involved in the development of both conditions.

Sometimes these links are more obvious. Back in 2009, a team of psychologists from Northwestern University, Illinois, decided to check if antidepressants might be affecting our personalities. In particular, the team were interested in neuroticism. 

For the study, the team recruited adults who had moderate to severe depression. They gave one third of the study’s participants the antidepressant paroxetine (a kind of selective serotonin reuptake inhibitor (SSRI)), one third a placebo, and one third talking therapy.

“We found that massive changes in neuroticism were brought about by the medicine and not very much at all by the placebo [or the therapy],”

In other contexts, this would be considered a success, since a reduction in neuroticism would improve depression.

The big surprise was that, though the antidepressants did make the participants feel less depressed, the reduction in neuroticism was much more powerful – and their influence on neuroticism was independent of their impact on depression. The patients on antidepressants also started to score more highly for extroversion.

This puzzles me because I’ve been taking antidepressants over 30 years and am still more “neurotic” than most, always needing everything to be in my very narrow range of physical tolerance (thanks, EDS). 

While becoming less neurotic might sound like an appealing side-effect, it’s not necessarily all good news.

That’s because this aspect of our personalities is something of a double-edged sword; yes, it’s been associated with all kinds of unpleasant outcomes, such as an earlier death, but it’s also thought that anxious over-thinking might be helpful.

For example, neurotic individuals tend to be more risk-averse, and in certain situations worrying can improve a person’s performance.

I misunderstood what was meant by “helpful” until I realized that in this description, “anxious over-thinking” only refers to worrying, not anxiety.

True anxiety is only destructive and never helpful because it’s based on our inner imagination, not external reality.

At this point it’s worth pointing out that no one is arguing that people should stop taking their medication. Despite their subtle effects on the brain, antidepressants have been shown to help prevent suicides, cholesterol-lowering drugs save tens of thousands of lives every year, and paracetamol is on the World Health Organisation’s list of essential drugs because of its ability to relieve pain. But it is important that people are informed about any potential psychological side-effects.

Most people won’t have these side-effects but a few will have extreme reactions, and this extremely large variability is exactly what population-level studies obscure.

My strangest experience was that an antibiotic I was prescribed for a dog bite had the side effect of making me incredibly anxious. Luckily, I thoroughly researched all possible side effects and found anxiety listed. As soon as I requested a change to a different antibiotic, my anxiety went back down to my normal level.

What bothers me is that no medical professional found my reaction particularly unusual, which seems like they’ve seen it before, yet I had to dig pretty deep online to find this obscure side effect and validate my experience.

The matter takes on a whole new urgency, when you consider that some personality changes can be dramatic.

There’s solid evidence that the drug L-dopa, which is used to treat Parkinson’s disease, increases the risk of Impulse Control Disorders (ICDs) – a group of problems that make it more difficult to resist temptations and urges.

Consequently, the drug can have life-ruining consequences, as some patients suddenly start taking more risks, becoming pathological gamblers, excessive shoppers, and sex pests.

The association with impulsive behaviours makes sense, because L-dopa is essentially providing the brain with a dose of extra dopamine, …and the hormone is involved in providing us with feelings of pleasure and reward.

in order to minimise any undesirable effects and get the most out of the staggering quantities of medications that we all take each day, Mischkowski reiterates that we need to know more. Because at the moment, he says, how they are affecting the behaviour of individuals – and even entire societies – is largely a mystery. 

I suspect that a lot of the confusion about whether opioids are effective or not is because our society looks only at populations, not at individuals, when designing and implementing healthcare policy. And this hides many dramatic and even dangerous effects of whatever drug or therapy is being taken.

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