A new analysis of the cause of depression has seemingly upended what we know about this common condition and calls into question the use of antidepressants. But it can also leave patients with more questions than answers as the science evolves. An umbrella systematic review of 17 studies published in Molecular Psychology On July 20 he examined the decades-old theory that depression is caused by low serotonin and found that there was “no solid 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 questioned it, believing it oversimplified a complex condition. “The serotonin theory is very old and has been 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, probably a little earlier, there have been rumors that actually the evidence is not very strong or is inconsistent. Some studies are positive, some are negative, but nobody really has 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 took their conclusion a step further, suggesting that antidepressants are ineffective in treating depression – and have largely acted as a placebo. “Evidence from placebo-controlled trials shows that antidepressants are little better than a sugar pill,” he said. “And if that small difference isn’t about correcting a chemical imbalance, improving low serotonin levels, what is?” The research gives an exciting insight that depression is not only caused by low serotonin. Many experts say that’s already widely accepted, and that it’s also true that antidepressants can be extremely beneficial for some patients — even if we don’t know exactly why. Where does this leave patients and doctors, and could the analysis affect how we treat depression in the future?
Are antidepressants effective against depression?
Antidepressants are widely believed to affect the behavior of neurotransmitters, chemical messengers in the brain such as serotonin and dopamine, in a way that can change emotions and mood to help improve symptoms of depression in some patients. WATCHES | Living alone during the pandemic can worsen anxiety, depression:
Living alone during the pandemic can worsen anxiety, depression
Continued physical distancing precautions due to the COVID-19 pandemic can exacerbate anxiety and depression, especially for people living alone. People with depression may experience a wide range of symptoms, including persistent feelings of sadness and hopelessness, changes in appetite, sleep deprivation, fatigue, irritability, and loss of interest in hobbies and social relationships that can affect daily life. Although it is not clear exactly how antidepressants work on a biological level to relieve these symptoms, it is clear that they can still be extremely helpful in some patients. “It’s a typical discovery in medicine — you find a drug that works, but you don’t know exactly why,” said Dr. Phil Cowen, professor of psychopharmacology at the University of Oxford. “[The review] it’s an exercise in debunking and in a way, they criticize earlier studies that were difficult to do,” he said. [older] The studies, clearly, were very indirect and they’re messy, and I don’t think anyone thought they were that great.” Moncrieff’s team found that some depressed patients actually had higher levels of serotonin in certain areas of the brain, and in some cases long-term use of antidepressants could actually reduce the amount of serotonin – although the findings were “inconsistent”. “I think it makes a huge difference, because the how [antidepressants] Labor really affects whether they work,” he said. “It affects how useful we think they are.” The findings caused quite a stir in the media and scientific community, with hundreds of news outlets covering the study—quickly landing it in the top five percent of all research rated by Altmetrica company that analyzes where published research is shared. Findings of this perceived magnitude could have a seismic impact on how we understand and treat a widespread condition like depression, which affects about one in eight Canadians at some point in their lives. While research is challenging the very nature of what we know about depression, many doctors are reluctant to change the way we treat it.
Antidepressants can be a “lifesaver” for some
Dr. David Juurlink, chief of clinical pharmacology at Sunnybrook Health Sciences Center in Toronto, said he was not surprised by the findings because the chemical imbalance theory of depression is now widely seen as an “obvious oversimplification” of a complex condition. “Although I think doctors prescribe serotonin-enhancing antidepressants too often, in part because of this oversimplification, it’s important to recognize that they actually improve the well-being of some patients,” he said in an email. “Exactly how they do this is not as clear as we are led to believe.” A bottle of anti-depressants is displayed in Miami, Florida. A new analysis shows that depression is not caused by low serotonin and that antidepressants are ineffective in treating it. (Joe Raedle/Getty Images) Dr. David Gratcher, a psychiatrist and attending physician at the Center for Addiction and Mental Health (CAMH) in Toronto, said he wasn’t surprised by the findings — just that they got as much attention as they did. “This suggestion that depression is all about serotonin has not been accepted by psychiatrists for many years, probably many decades,” he said, adding that researchers are “terribly biased” in their evaluation of antidepressants. “Their paper shows that things are much more complicated than serotonin—not surprisingly—and then they turn around and say, ‘See, this is another example of the fact that antidepressants don’t really work.’” One doesn’t necessarily beget the another”. 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. “That’s not going to change. These drugs work,” he said. “An antidepressant is not necessary [recommended] to everyone with depression – some people may actually do better with talk therapy – but it’s definitely a tool in our tool kit and, to be honest, it’s a lifesaver for some of our patients.”
Research questions antidepressants
Moncrieff said the research found that another way antidepressants may work is by desensitizing the brain to negative emotions associated with depression. In theory, this could also affect other emotions. He said one of the effects that previous studies have reported on patients is “emotional numbing,” where they not only lack unwanted feelings like depression and anxiety, but positive feelings like joy and happiness. “There may be some people who feel this is an outcome they want. But I think in general, people are not going to want to be emotionally numb, not for long periods of time anyway, and so I think it completely changes the kind of decisions people might make about antidepressants,” Moncrieff said. Chris Davey, head of psychiatry at the University of Melbourne, said in an email that undermining the trust people with depression have in their treatments can be “very damaging”. “People will stop their medication suddenly, without supervision,” he said, “which can cause a dramatic deterioration in their mental health.” Davey said he was concerned that the paper diminished a treatment option that can be incredibly beneficial for some patients, especially when alternatives may not always be available to those at risk of severe depression. WATCHES | Research shows that exercise can help alleviate pandemic depression:
Research shows how exercise has helped fight pandemic depression
A study conducted by BC researchers during the COVID-19 pandemic showed how exercise, specifically a combination of yoga and high-intensity exercise, helped fight depression – supporting decades of research on how exercise improves mental health. “This [research] it should make no difference in the treatment of depression. I hope it makes people realize that depression is a very complex condition and that there are no simple explanations for it,” said Davey. “Everyone should know that improving their diet, getting more exercise and paying attention to their sleep can be helpful. Everyone should have access to psychotherapy. And for those people for whom these things don’t help, then we think medicines.” Gratzer said there are many new areas of research into treatment options for depression that may be beneficial, including new ways to deliver psychotherapy, emerging medications and discoveries such as the use of ketamine. Ketamine is a general anesthetic first approved in Canada in the 1960s for medical or veterinary procedures, as well as a psychedelic party drug sold on the illegal market. It is also increasingly used as a fast-acting and effective treatment for depression at low doses, as it works to repair synapses in the brain that are damaged by stress. There is “an understanding that certain life experiences may be more connected, and so the research is very active. Maybe at the end of the day, we’ll understand that depression is not a disease,” Gratzer said. “As is often the case with mental health care, these are early days.”
