Aug 25th 2022

Chemical imbalance theory of depression: clearing up some misconceptions

 

The scale of the response to our recent study finding that there was no support for the idea that low serotonin causes depression – the so-called “chemical imbalance” theory of depression – was enormous. Our paper is one of the 400 most shared of the 21 million papers that have ever been tracked. And our article in The Conversation was read by more than 1.3 million people. However, we feel that some of the responses missed the point, and we’d like to address those points here.

The main response from leading psychiatrists was that antidepressants work and it does not matter how. However, whether antidepressants work is not clear-cut, and how they produce their effects matters.

But first, we want to highlight a point skipped over by many commentators: for decades, people, including doctors, have been misled by false claims about what antidepressants are doing. The marketing line that antidepressants correct an underlying chemical imbalance has influenced people’s choices about their treatment, their self-perception, and their outlook on recovery.

We should acknowledge that people were misled and take stock of how corporate interests and marketing have affected medical discussions, otherwise we will be condemned to repeat these mistakes with new pharmaceutical products. For example, various unsubstantiated theories are currently circulating about how esketamine might rectify other chemical imbalances or other brain abnormalities.

Many people taking antidepressants get better, but whether they work or not is contested. The evidence for antidepressants’ effectiveness comes from randomised trials that show that people improve when they are given an antidepressant or a placebo.

On average, antidepressants reduce depression scores slightly more than a placebo. But the difference is small: two points on a 52-point depression scale. Evidence from large analyses of patient responses and National Institute of Health and Care Excellence guideline committees suggests that this is not a big enough difference to be noticeable by patients or doctors.

Even this difference may be exaggerated because antidepressants cause side-effects and other more subtle changes that let people know they are taking the active drug rather than the placebo, which may lead to amplified placebo effects.

Furthermore, the studies of antidepressants last for six to eight weeks and cannot provide evidence of whether taking antidepressants for longer periods is worthwhile, especially the months and years that many people take them for.

But even if we accept that the small difference between antidepressants and placebo is a real effect of the drug, there is no reason to assume, as many experts do, that it reflects the action of antidepressants on some underlying biological mechanism of depression.

Possible explanations for antidepressants small effect

First, although brain biology is involved in everything we think and feel, there are no established specific biological causes of depression. Other proposed ways in which antidepressants might target underlying mechanisms are hypotheses, often drawn from animal studies or cells in a dish and none have been consistently demonstrated in humans.

Second, there is another explanation for what antidepressants do. Antidepressants are drugs that change brain chemistry, and like other drugs that do this, they produce changes in our mental states and experiences. These changes can temporarily override our current feelings.

For example, alcohol has sedative and relaxing effects that can reduce anxiety and briefly “drown your sorrows”, but this is not because alcohol works on the underlying mechanisms of anxiety or depression. Alcohol’s effects (with individual variation) are experienced by everyone and not just people with one of these diagnoses.

Antidepressants do not commonly make people merry like alcohol can. They cause a variety of more or less subtle mental alterations, depending on the chemistry of the drug. One common, dose-dependent alteration, is numbing of emotions.

This effect could also explain why antidepressants perform a little better than placebo in randomised trials. In the short term, the numbing may make people feel less depressed, but in the long term, the benefits are less clear.

This is why drawing analogies between antidepressants and paracetamol – as one commentator has done – is misleading. Paracetamol does not produce significant mental changes, and hence these cannot account for its effects on pain.

Unlike depression, we know there are specific biological mechanisms that produce pain, and we can therefore conclude that paracetamol is working through modifying these, even if we do not know exactly how it does so.

The mechanism of action of antidepressants is crucially important for considering the pros and cons of taking them, especially in the long term, given that we only have short-term trial data.

The idea that antidepressants correct an underlying chemical or other problem in the brain is reassuring – we do not have concerns about the long term use of insulin in diabetics. But if antidepressants are changing brain chemistry, without evidence they are rectifying anything, this is a different situation.

Other drugs that affect the way we feel and think by altering brain chemistry, such as alcohol and other recreational drugs, can cause concentration problems, sleep disturbance and withdrawal symptoms when they are used for long periods – all of which are concerns for antidepressants.

Lastly, we know more about what causes depression than is often thought. The number of stressors in life – job loss, relationship breakdown, physical illness – strongly predicts who will become depressed.

An over-emphasis on looking for the chemical equation of depression may have distracted us from its social causes and solutions. We suggest that looking for depression in the brain may be similar to opening up the back of our computer when a piece of software crashes: we are making a category error and mistaking problems of the mind for problems in the brain.

It would be wise to observe caution with drugs whose effectiveness is not certain, whose mode of action is unknown, and which have many side-effects, especially for use in the long term.

 

Mark Horowitz, Clinical Research Fellow in Psychiatry, UCL and Joanna Moncrieff, Professor of Critical and Social Psychiatry, UCL

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Sep 29th 2022
EXTRACTS: "For many of us, some personality traits stay the same throughout our lives while others change only gradually. However, evidence shows that significant events in our personal lives which induce severe stress or trauma can be associated with more rapid changes in our personalities." ----- "Over time, our personalities usually change in a way that helps us adapt to ageing and cope more effectively with life events." ----- " ....participants in this study recorded changes in the opposite direction to the usual trajectory of personality change." --- "....you might like to take the time to reflect on your experiences over the past few years, and how these personality changes may have affected you."
Sep 21st 2022
EXTRACTS: "It might seem like an obscure footnote among the history-making events of 2022, but the year of Queen Elizabeth II’s death coincides with the 300th anniversary of Adam Smith’s birth." ----- "As a committed Stoic, Smith had little patience for greed. The whole point of Roman Stoic philosophy was to use personal moral discipline to support the rule of law and constitutions, and to make society a better place." ----- "When we read Smith, we are better served to think of the example of Elizabeth II than of those driven by personal greed. It might sound archaic, but, as Britons’ response to her death suggests, these values still appeal to a great many people today."
Sep 14th 2022
EXTRACT: "On the day of Queen Elizabeth II’s death, the former Prince of Wales was proclaimed King Charles III. Although it’s been known for decades that Charles would succeed his mother, there were rumours that he might, once king, choose the name George due to the contentious legacies of Kings Charles I and Charles II."
Aug 25th 2022
EXTRACT: "An over-emphasis on looking for the chemical equation of depression may have distracted us from its social causes and solutions. We suggest that looking for depression in the brain may be similar to opening up the back of our computer when a piece of software crashes: we are making a category error and mistaking problems of the mind for problems in the brain. It would be wise to observe caution with drugs whose effectiveness is not certain, whose mode of action is unknown, and which have many side-effects, especially for use in the long term."
Jul 29th 2022
EXTRACTS: "China uses incarcerated prisoners of conscience as an organ donor pool to provide compatible transplants for patients. These prisoners or “donors” are executed and their organs harvested against their will, and used in a prolific and profitable transplant industry."
Jul 29th 2022
EXTRACT: "In the first episode of season three of The Kominsky Method (2021), there is a funeral service for Michael Douglas’ character’s lifelong friend Norman Newlander (played by Alan Arkin). By far the most inconsolable mourner to give a eulogy is Newlander’s personal assistant of 22 years who, amid a hyperbolical outpouring of grief, literally cannot bring herself to let go of the casket. It is a humorous scene, to be sure, but there is something else going on here that is characteristic of employer-employee relations in this era of neoliberal capitalism. “Making him happy made me happy,” she exclaims, “his welfare was my first thought in the morning, and my last thought before I went to sleep.” That isn’t sweet – it is pathological. ----- Employee happiness is becoming increasingly conditional on, or even equated with, the boss’ happiness. As Frédéric Lordon observes in his book, Willing Slaves of Capital (2014), “employees used to surrender to the master desire with a heavy heart…they had other things on their minds…ideally the present-day enterprise wants subjects who strive of their own accord according to its norms.” In a word, the employee is increasingly expected to internalize and identify with the desire of the master."
Jul 20th 2022
EXTRACT: "For three decades, people have been deluged with information suggesting that depression is caused by a “chemical imbalance” in the brain – namely an imbalance of a brain chemical called serotonin. However, our latest research review shows that the evidence does not support it."
Jul 13th 2022
"But is he “deluded”? " ---- "....we sometimes end up with deluded leaders because we ourselves can be somewhat delusional when we vote." ---- "David Collinson, a professor of leadership and organization at Lancaster University, associates this predicament with excessive positive thinking, or what he calls “Prozac leadership,” in reference to the famous antidepressant that promises to cheer people up without actually fixing what is wrong in their lives. “ ---- "In politics, Prozac leaders come to power by selling the electorate on wildly overoptimistic views of the future. When the public buys into a Prozac leader’s narrative, it is they who are already verging on the delusional." ----- "Another potential example is Vladimir Putin, who has conjured a kind of nostalgic dream world for his followers and the wider Russian public."
Jun 25th 2022
EXTRACT: "Many veterans, refugees and other people who have experienced trauma and have mental health issues spend little time thinking about the future. Instead, they are narrowly focused on the negative past. However, people who have experienced trauma and developed a healthy future perspective report being better at coping with life, having fewer negative thoughts about the past, and getting better sleep compared with those who have a negative future perspective. So, instead of dwelling on the past, people who have suffered trauma should be encouraged to think about the future and set goals that help them develop hope for a good life."
Jun 8th 2022
EXTRACT: " The devastation of war is a recurring theme in Turner’s work, and unlike his contemporaries Turner is willing to forego the occasion to bolster national pride or the patriotism of its fallen heroes. In “The Field of Waterloo” (1818), Turner’s great tragic vision of war, “The…  dead of both sides lay intertwined, nearly indistinguishable surrounded by the gloom of night.” Near the bottom center there are three women. The one farthest from us is bearing a child and in her right hand a torch which illumines the sea of mangled bodies. Beside her is another woman struggling to keep a third (also with child) from collapsing outright. Turner reflects not only on the dead and dying, but on the widows and orphans that war produces."
May 19th 2022
EXTRACTS: "Thus experimental creativity could be witnessed, but not verbalized.  When five leading Abstract Expressionist painters founded an art school in New York in the late 1940s, they offered no formal courses, because, as Robert Motherwell explained, "in a basic sense art cannot be taught." ------ "Conceptual artists are ...... more inclined to use written texts to accompany their works in other genres.  In 1883, Vincent van Gogh wrote to his brother, "One of these days I will write you a letter;  I shall write it carefully and try to make it short, but say everything I think necessary."
May 17th 2022
EXTRACT: "Unfortunately, it’s common for dark triad personalities to become leaders. ..... their ruthlessness and ability to manipulate means they attain positions of power quite easily. When a “dark” leader attains power, conscientious, moral people rapidly fall away. A government operating under these conditions soon becomes what the Polish psychologist Andrzej Lobaczewski called a “pathocracy” – an administration made up of ruthless individuals devoid of integrity and morality. This happened with Donald Trump’s presidency, as the “adults in the room” gradually headed for the exit, leaving no one but staffers defined by their personal allegiance to Trump. A similar decay in standards has occurred in the UK."
May 11th 2022
EXTRACT: "The proportion of US electricity deriving from wind and solar in the month of April climbed to 20%. Thus, the renewables total was 26.5 if we add in hydro. This statistic is unprecedented."
Apr 24th 2022
EXTRACT: "Every year, around 12,000 men in the UK die from prostate cancer, but many more die with prostate cancer than from it. So knowing whether the disease is going to advance rapidly or not is important for knowing who to treat." ...... "For some years, we have known that pathogens (bacteria and viruses) can cause cancer. We know, for example, that Helicobacter pylori is associated with stomach cancer and that the human papillomavirus (HPV) can cause cervical cancer." ....... "....we have identified five types (genera) of bacteria linked to aggressive prostate cancer." ...... "We examined prostate tissue and urine samples from over 600 men with and without prostate cancer," ..... "....men who had one or more of the bacteria were nearly three times more likely to see their early stage cancer progress to advanced disease, compared with men who had none of the bacteria in their urine or prostate."
Apr 13th 2022
EXTARCTS: "Steve Jobs dreaded turning 30, because he knew it would be fatal to his creativity: "It's rare that you see an artist in his 30s or 40s able to contribute something amazing." ....... "When Ford introduced the Model T, he was 45 years old" ...... "Ford’s Model T arrived only after a series of earlier cars – Models A, B, C, K, N, R, and S." .... "Sam Walton opened Wal-Mart No. 1 in Rogers, Arkansas, at 44, and discovered “that there was much, much more business out there in small-town American than anybody, including me, had ever dreamed of.” At 53, Warren Buffett wrote in his annual letter to Berkshire Hathaway shareholders that “your chairman, always a quick study, required only 20 years to recognize how important it was to buy good businesses.” "
Mar 29th 2022
EXTRACT: ".... Christie's web site calls Shot Sage Blue Marilyn [1964], to be auctioned in May, 'among the most iconic paintings in history', " ------ "Andy Warhol's annus mirabilis was not 1964, but 1962. This is recognized both by the market and by scholars. Thus in a paper published in the Journal of Applied Economics, Simone Lenzu and I found that in all auctions held during 1965-2015, the average price of Warhol's paintings executed in 1964 was significantly lower than the average price of those he made in 1962. And in a survey of 61 textbooks of art history published during 1991- 2015, whose authors included such eminent scholars as Martin Kemp and Rosalind Krauss, we found that fully 45% of the total of 137 illustrations of Warhol's paintings were of works from 1962, compared to only 12% of works from 1964. Thus not only do collectors value Warhol's works of 1962 more highly than those of 1964, but so do scholars of art history,.... "
Mar 29th 2022
EXTRACTS:".....there is plenty of space to scale. For internet-based businesses, the addressable total market is often large. In many areas, such as software, it spans the globe. Chinese estimates indicate that the average distance between seller and buyer on e-commerce platforms is roughly 1,000 kilometers (621 miles), compared to five kilometers for a traditional retail or service business." ------- "While the internet has removed many geographical barriers, high-growth companies cannot emerge just anywhere. In fact, though such firms can be found in more countries than ever, they remain concentrated in entrepreneurial hotspots. For example, of the 24 unicorns in Germany (as of March 2022), 17 are based in Berlin and five in Munich. Of France’s top 24 unicorns, 19 are based in Paris and one in a Paris suburb." ------ "Tech entrepreneurship has become global, but its beating heart remains local."
Mar 27th 2022
EXTRACTS: " We are supposed to be living in a post-ideological era, where everyone one is a cynic, not so gullible as to believe in anything anymore, least of all in the quaint notion of objective truth. This rejection of truth as such is among the great disasters to have befallen our relations with each other and between nations.  We appear to be beyond truth’s demise – we are now witnessing its unpleasant putrefaction and decay." ------ " If we want to grasp how ideology functions in America today, there is no better place to look than at the phenomenon of Trumpism. While he may be only a symptom, Trump himself is the quintessential embodiment of America’s moral and epistemic decline. " ------ "By its disavowal of truth and perpetuation of lies for the sake of self-aggrandizement, Trumpism represents an existential threat to this country and to the future of the Republic. It is a cancer that threatens whatever is good and decent in American life. " ----- "All they know is negative freedom – freedom from – but ignore the need for positive freedom, the freedom to… as in the freedom to flourish, to realize oneself in the world; to make and re-make oneself and the world through action."
Feb 14th 2022
EXTRACT: "In the decades since its inception, there has been heavy criticism directed towards the War on Drugs. These complaints include the increased incarceration rates, the increase in the number of prisoners in jail due to nonviolent offenses, uneven sentencing guidelines often based on the drug type and race, and suggestions of a racist component in terms of who was targeted by law enforcement. Various studies show that instead of reducing crime, the strict sentencing guidelines created more criminals and undermined many of the communities most strictly targeted by law enforcement. Long sentences for non-violent offenses made it difficult for those released to find work and weakened their bonds with family and their broader community."
Feb 2nd 2022
EXTRACT: "......... there are countries that have had a relatively high number of infections but which have still managed to keep their death numbers low – countries like Japan. It’s had 17,612 infections per million people yet only 146 deaths per million. This is despite almost one in three people in Japan being over the age of 65 and so at greater risk of severe COVID (the average age of people dying from COVID is over 80). What has kept the death rate there down? A recent Japenese study has proposed an answer. It reports that the risk of people dying of COVID in Japan is related to the microbes present in their guts. "