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Five unanswered questions about antidepressants and depression

Whether antidepressants are a good option for relieving depression is in the spotlight again, in a new book, Chemically Imbalanced, by one of the medicines’ leading critics, British psychiatrist, Dr Joanna Moncrieff

This is Everyday Science with Clare Wilson, a subscriber-only newsletter from The i Paper. If you’d like to get this direct to your inbox, every single week, you can sign up here.

Hello, and welcome back to Everyday Science.

I have recently been absorbed by a new book about antidepressants, out this week, called Chemically Imbalanced: The making and unmaking of the serotonin myth.

Antidepressants are one of the most commonly used medicines in most western countries, with nearly one in six people in England taking these drugs. Many people find them invaluable.

The book, by Dr Joanna Moncrieff, a psychiatrist at University College London, overturns the usual explanation given for how the medicines work.

She also claims the drugs are being overused as a quick fix for people who are really experiencing understandable mental distress in response to difficult life experiences, and who might be better helped in other ways.

Dr Moncrieff’s views do not reflect those of most mainstream mental health experts. The Royal College of Psychiatrists, for instance, says antidepressants are a “recommended therapeutic option” for severe depression or for milder forms of the illness if people don’t respond to talking therapies.

Dr Awais Aftab, a psychiatrist at Case Western Reserve University in Cleveland in the US, has described Dr Moncrieff’s book as “one contrarian psychiatrist’s controversial opinions that are well outside the clinical and scientific consensus”.

But Dr Moncrieff’s views are shared by some other mental health professionals, some of whom are part of a loose and informal movement called “Critical Psychiatry”, which argues for less psychiatric medication use generally.

The dispute highlights that there are still several unanswered questions around depression – and the drugs used to treat it – that are dividing mental health experts.

How do antidepressants work?

The most commonly cited explanation for how antidepressants work has long been that they correct a chemical imbalance in the brain.

The theory went that depression is caused by the lack of a brain signalling molecule that is thought to affect mood called serotonin – and that antidepressants raise serotonin back to normal – hence the name of the most common type of such drugs, selective serotonin reuptake inhibitors, or SSRIs, the best-known of which is Prozac.

The idea has become so widespread that serotonin has become a byword for a “happy chemical”. When people are weighing up whether to start or stop taking antidepressants, the idea of topping up your serotonin is often seen to be as necessary as someone with diabetes taking insulin.

But in 2022, Dr Moncrieff and others published a review of previous research that found there is no good evidence that people with depression have lower serotonin in their brains. It upset some people who take antidepressants, who felt they had been misled.

In fact, the chemical imbalance theory of depression was already falling out of favour among psychiatrists and researchers, even before Dr Moncrieff’s review.

How might SSRI antidepressants really work? Animal research shows that they do, in fact, raise serotonin levels, but they have several other biochemical effects on the body (as do many pharmaceuticals).

Potential alternative explanations include that they spur the growth of new brain cells, or that they calm inflammation in the brain – although both these theories are at an early scientific stage.

Dr Moncrieff, on the other hand, says antidepressants should be seen more like alcohol or sedatives, which induce an altered state of mind but don’t correct an underlying problem. That alteration could be a general numbing of emotions, both positive and negative ones. This effect is often reported by both people with depression and healthy volunteers who are given antidepressants in research studies.

Other critics of Dr Moncrieff such as Professor Carmine Pariante, a psychiatrist at King’s College London, say it doesn’t really matter if the chemical imbalance theory is wrong – as long as antidepressants help people.

What causes depression?

If we are to understand how antidepressants work, it would help if we know what causes depression in the first place – but we don’t.

In the field known as “biological psychiatry”, there are efforts to understand depression in terms of altered levels of brain signalling molecules – there are many other such candidates as well as serotonin – genetic predispositions or faulty electrical activity in different sites in the brain.

So far, though, no convincing evidence has emerged to support any such particular theory.

Dr Moncrieff said in her book that this is too simplistic a way to understand anything as complex as the human mind.

She said that depression is best understood as a response to bad experiences, such as unemployment, poverty or abuse. “This is how psychiatry thought about mental disorders for much of the 20th century – as meaningful, human reactions to stressful, undermining or threatening situations,” she said.

Most psychiatrists would say that even if we haven’t yet figured out the details, depression must still be caused by biological mechanisms in the brain. Even if it’s all down to distressing life events, said Professor Pariante, “they need the brain to exert the effect”.

How serious are the side effects?

Like all medicines, antidepressants can have unwanted side effects. They vary a lot by person, and can include weight gain, loss of libido, drowsiness and insomnia. But the problems generally improve with time, and depending on how bad they are, users might feel these downsides are worth the improvements in mood.

But some people have reported a complete loss of sex drive that continues even after someone has stopped taking antidepressants.

And antidepressants can more rarely cause severe anxiety, agitation and even suicidal impulses when they are first started.

“Young people under 25 seem particularly at risk,” says the NHS website. It advises people who start taking the medicines to tell a relative or close friend, who could watch out for any such changes.

How long should you take antidepressants for?

Much of the recent rise in the number of people who are taking antidepressants stems from an increase in people using the drugs indefinitely – rather than a rise in the number of people starting their use.

“I share concerns that people are staying on antidepressants for longer periods than they need,” said Professor Pariante. “There’s definitely more work that we can be doing in encouraging people to stop antidepressants after they’ve become well again.”

Medical guidelines say that after a first episode of depression, if someone has felt well for six to 18 months, it is worth trying to stop taking the medicines, gradually, and under a doctor’s guidance.

But some people don’t want to risk stopping in case their depression returns, said Professor Pariente. “These are individual decisions.”

Dr Moncrieff says that the chemical imbalance theory has contributed to people being willing to take antidepressants for long periods of time, even lifelong. “Research shows people who think that depression is caused by a chemical imbalance are more likely to be on long-term medication and think that they can’t stop,” she said.

How hard is it to stop antidepressants?

Stopping antidepressants can trigger withdrawal symptoms, from headaches, and nausea to psychological ones, including anxiety and a return of depression symptoms.

They can also include severe agitation and suicidal impulses, so it is important that people planning to stop get their doctor’s advice on how to slowly reduce their dose.

The problem of withdrawal symptoms did not used to be well recognised, but in 2019, the Royal College of Psychiatrists rewrote its website, saying that withdrawal can be severe and prolonged for some.

Professor Pariente says that alarmist coverage of Dr Moncrieff’s claims may cause some users to abruptly stop taking antidepressants without their doctor’s help. “It’s almost ironic that more problems could be created by this,” he said.

But although withdrawal symptoms are now more acknowledged, there is still debate over how common they are. Last year a paper came out claiming the problem affects only one in six people who stop taking the medicines, with only 3 per cent of the total severely affected.

Dr Moncrieff points out that this review covered people who had been taking the medicines for an average of six months – a shorter period than most take the medicines for before they try to stop, and withdrawal symptoms seem to be worse if someone has been taking the medicines for longer.

I’ve also written

We are constantly hearing that we need to switch over our home heating systems from gas boilers to electricity-powered heat pumps.

The main reason for this messaging is that the Government needs this to happen to reduce the UK’s carbon emissions. But there are other reasons to consider the switch, as I explain here.

I’ve been reading

For The i Paper book club, I’ve been reading Intermezzo, by Sally Rooney. After a slow start, I eventually became engrossed and stayed up reading it far too late into the night, sometimes having to stifle my sobs (in a good way).

This is a must for anyone who has experienced love, death, annoying siblings – or plays chess.

This is Everyday Science with Clare Wilson, a subscriber-only newsletter from The i Paper. If you’d like to get this direct to your inbox, every single week, you can sign up here.



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