This is an excerpt from Second Opinion, a weekly analysis of health and medical science news. If you have not yet subscribed, you can do so by clicking over here.
A new analysis of the cause of depression appears to have overturned what we know about this common condition and challenged the use of antidepressants. But it may also leave patients with more questions than answers as science develops.
A comprehensive systematic review of 17 studies published in Molecular Psychology On July 20, we looked at the old theory that depression is caused by low serotonin, and found that “there is no consistent evidence” for an “association between serotonin and depression.”
The theory that depression is caused by a chemical imbalance in the brain has been around since the 1960s. But for years, many experts have questioned this, feeling it oversimplifies a complex case.
“The serotonin theory is very old and very popular since the 1990s, when the pharmaceutical industry started promoting it,” said Dr Joanna Moncrieff, Professor of Psychiatry at University College London and lead author of the study.
“But since about 2005, maybe a little bit before that, there’s been some kind of rumor that the evidence is actually not very strong, or it’s inconsistent. Some studies are positive, some studies are negative, but no one is getting that evidence together anywhere.” “
Moncrieff and her team set out to challenge the serotonin theory in a systematic review of the available research. They also went further in their conclusion by noting that antidepressants are ineffective in treating depression – and they have worked largely as a placebo.
“Evidence from placebo-controlled trials shows that antidepressants are slightly better than sugar pills,” she said. “And if that simple difference isn’t about correcting a chemical imbalance, improving low serotonin levels, what do we do?”
The research paints a compelling picture that depression is not caused by low serotonin alone. Many experts say this is already widely accepted and that it’s also true that antidepressants can be very helpful for some patients – even if we don’t know exactly why.
So where does this leave patients and doctors, and can the analysis affect the way we treat depression in the future?
Are antidepressants effective against depression?
It is widely believed that antidepressants affect the behavior of neurotransmitters, chemical messengers in the brain such as serotonin and dopamine, in a way that can alter emotions and mood to help improve depression symptoms in some patients.
Watch | Living alone during a pandemic can exacerbate anxiety and depression:
Ongoing physical distancing precautions due to the COVID-19 pandemic can exacerbate anxiety and depression, especially for people who live alone.
People with depression can experience a wide range of symptoms, including persistent feelings of sadness and hopelessness, changes in appetite, sleep deprivation, fatigue, irritability, and a loss of interest in hobbies and social relationships that can affect daily life.
While it is not clear exactly how antidepressants work on a biological level to relieve these symptoms, it is clear that they are still very beneficial for some patients.
“It’s a typical finding in medicine – you find a drug that works, but you don’t quite know why,” said Dr Phil Quinn, professor of psychopharmacology at the University of Oxford.
“[The review] It is an exercise in debunking and in a way, they criticize older studies that were difficult to do. ” [older] The studies were obviously very indirect and messy, and I don’t think anyone thought they were cool.”
Moncrieff’s team found that some depressed patients actually have higher levels of serotonin in certain areas of the brain, and in some cases long-term use of antidepressants can reduce the amount of serotonin – although the results have been “inconsistent”.
“I think it makes a huge difference, because how [antidepressants] She said that work actually affects whether they work. “It affects how much help we think is helpful.”
The findings caused quite a stir in the media and the scientific community, with hundreds of news outlets covering the study — and it quickly ranked in the top five percent of all research it scored. metrica company that analyzes where published research is shared.
Findings of this perceived magnitude could have a seismic effect on the way we perceive and deal with a pervasive condition such as depression, which affects the estimation of One in eight Canadians at some point in their lives.
While research questions the nature of what we know about depression, many clinicians are hesitant to change the way we approach depression.
Antidepressants can be a lifesaver for some
Dr. David Gorlink, chief of clinical pharmacology at Sunnybrook Health Sciences Center in Toronto, said he was not surprised by the results, because the chemical imbalance theory of depression is now widely seen as an “obvious oversimplification” of a complex condition.
“Although I believe clinicians prescribe serotonin-boosting antidepressants more often, in part because of this oversimplification, it is important to acknowledge that they do indeed improve the well-being of some patients,” he said in an email.
“How exactly they do it is not as clear as we think.”

Dr. David Gratzer, MD, a psychiatrist and therapist at the Center for Addiction and Mental Health (CAMH) in Toronto, said he wasn’t surprised by the results — only that they got as much attention as they did.
“This suggestion that depression is about serotonin all the time has not been accepted by psychiatrists for many years, and possibly many decades,” he said, adding that researchers are “terribly biased” in their assessment of antidepressants.
“Their paper shows that things are a lot more complicated than serotonin – no surprise – and then they turn around and say, ‘You see, this is another example of the fact that antidepressants don’t really work.'” One does not necessarily give rise to the other.”
Gratzer said he still regularly prescribes antidepressants as a treatment option for depression, and has no plans to stop doing so based on the research.
“This is not going to change. These drugs work,” he said.
Antidepressants are not necessarily [recommended] In everyone with depression – some people may actually do better with talk therapy – but it’s definitely a tool in our toolkit, and to be frank, it’s a lifesaver for some of our patients.”
Research calls antidepressants into question
Moncrieff said the research has found that another way antidepressants can work is by desensitizing the brain to negative feelings associated with depression. In theory, this could also affect other emotions.
One of the effects that previous studies have indicated on patients, she said, is “emotional sedation,” in which they not only have unwanted emotions like depression and anxiety, but positive emotions like joy and happiness.
“There might be some people who feel that’s the effect they want. But I think in general people wouldn’t want to be emotionally numb, not for long periods, anyway, so I think it totally changes the kinds of decisions,” Moncrieff said.
Undermining the confidence that people with depression have in their treatments can be “extremely harmful,” Chris Davey, chair of the University of Melbourne’s department of psychiatry, said in an email.
“People will stop taking medications suddenly and without supervision, which can cause a significant deterioration in their mental health,” he said.
Davey said he was concerned that the research paper undercut a treatment option that could be incredibly beneficial for some patients, especially when alternatives aren’t always available for those at risk for major depression.
Watch | Research shows that exercise can help relieve pandemic depression:
A study conducted by researchers in British Columbia during the COVID-19 pandemic showed how exercise, especially a combination of yoga and high-intensity exercise, helped fight depression — bolstering decades of research on how exercise improves mental health.
“this is [research] It shouldn’t make any difference in treating depression. I hope it makes people realize that depression is a very complex condition, and that there are no simple explanations for it.”
“Everyone should know that improving their diet, exercising more, and taking care of their sleep can be beneficial. Everyone should have access to psychotherapy. For people who are not helped by these things, then we consider medication.”
Gratzer said there are many new areas of research into potentially beneficial depression treatment options, including new ways to deliver psychotherapy, emerging medications, and discoveries such as the use of ketamine.
Ketamine is a general anesthetic that was first approved in Canada in the 1960s for medical or veterinary surgery, as well as a party anesthetic sold on the illegal market. It is also increasingly being used as a fast-acting, effective treatment for depression in low doses, by working to restore synapses in the brain that have been destroyed by stress.
“There is an understanding that some life experiences may be more related, so the research is very active. Perhaps at the end of the day, we will understand that depression is not a single disease,” Gratzer said.
“As is often the case with mental health care, these are early days.”
Discussion about this post