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A new analysis of the cause of depression appears to have changed what we know about this common condition and challenged the use of antidepressants. But it can also leave patients with more questions than answers as the science evolves.
A systematic review of 17 studies published in Molecular Psychology on July 20 looked at the decades-old theory that depression is caused by low serotonin and found that there was “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 doubted 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 lead author Dr Joanna Moncrieff, professor of psychiatry at University College London of the study
“But since 2005, probably a little before then, there’s been kind of a rumor that the evidence is actually not very strong or it’s inconsistent. Some studies are positive, some are negative, but no one really has such evidence gathered nowhere..”
Moncrieff and his team set out to challenge the serotonin theory in a systematic review of the available research. They also took their conclusion a step further by suggesting that antidepressants are ineffective in treating depression and have largely worked as placebos.
“Evidence from placebo-controlled trials shows that antidepressants are slightly better than a sugar pill,” he said. “And if this small difference has nothing to do with rectifying a chemical imbalance, improving low serotonin levels, what does it have to do with it?”
The research paints a compelling picture that depression is not caused by low serotonin alone. Many experts say that this is already widely accepted, and that it is also true that antidepressants can be extremely beneficial for some patients, although we don’t know exactly why.
So where does this leave patients and doctors, and could the analysis affect the way 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 ways that can alter emotions and mood to help improve symptoms of depression in some patients
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People with depression may face 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 connections that can affect everyday 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 very helpful for some patients.
“It’s a typical discovery in medicine: you find a drug that works, but you don’t quite know 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’re criticizing older studies that were difficult to do,” he said. [older] The studies were obviously very indirect and messy, and I don’t think anyone thought they were that big.”
Moncrieff’s team found that some depressed patients had higher levels of serotonin in certain areas of the brain, and in some cases long-term use of antidepressants could reduce the amount of serotonin, although the findings were “incoherent”.
“I think it makes a big difference, because how [antidepressants] work really influences whether they work,” he said. “It influences how helpful we think they are.”
The findings have caused quite a stir in the media and scientific community, with hundreds of media outlets covering the study, which quickly placed 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 one in eight Canadians at some point in their lives.
Although the research questions the very nature of what we know about depression, many doctors are hesitant to change the way we treat it.
Antidepressants can be “lifesavers” for some
Dr. David Juurlink, head of clinical pharmacology at Sunnybrook Health Sciences Center in Toronto, said he is not surprised by the findings, because the chemical imbalance theory for depression is now widely seen as an “obvious simplification.” for a complex disease.
“While I believe that doctors prescribe serotonin-enhancing antidepressants too often, in part because of this oversimplification, it is important to recognize that they actually improve well-being in some patients,” he said in an email.
“Exactly how they do it is not as clear as we’ve been led to believe.”
A bottle of antidepressants is shown in Miami, Florida. A new analysis suggests that depression is not caused by low serotonin and that antidepressants are ineffective in treating it. (Joe Raedle/Getty Images)
Dr. David Gratzer, 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 about serotonin all the time has not been accepted by psychiatrists for many years, probably many decades,” he said, adding that researchers are “terribly biased” in their assessment 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 antidepressants not really working.'” One doesn’t necessarily gives 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.
“That’s not going to change. These drugs work,” he said.
“An antidepressant isn’t necessarily an antidepressant [recommended] in everyone with depression (some people might actually do better with talking therapy), but it’s definitely a tool in our toolkit and, to be blunt, a lifesaver for some of our patients.” .
Research casts doubt on antidepressants
Moncrieff said the research found that another way antidepressants can work is to desensitize the brain to the negative emotions associated with depression. In theory, this could also affect other feelings.
He said one of the effects that previous studies have reported in patients is “emotional numbing,” where they not only lack unwanted emotions like depression and anxiety, but positive emotions like joy and happiness.
“There may be some people who feel like that’s an effect they want. But I think in general people won’t want to be emotionally numb, not for long periods anyway, and so I think it totally changes the type of decisions people could make about antidepressants,” Moncrieff said.
Chris Davey, the head of the department 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 go off their medication suddenly, without supervision,” he said, “which can lead to dramatic deterioration in their mental health.”
Davey said he worries the paper diminishes a treatment option that can be incredibly beneficial for some patients, especially when alternatives aren’t always available for those at risk for severe depression.
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“This [research] it should make no difference in the treatment of depression. I hope people will realize that depression is a very complex condition and there are no simple explanations,” said Davey.
“Everyone needs to 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, that’s when we think about the 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 surgery, as well as a psychedelic party drug sold on the illicit market. It is also increasingly used as a fast-acting and effective treatment for depression in low doses, working to restore synapses in the brain that are destroyed by stress.
There is “an understanding that certain life experiences might be more connected, and so the research is very active. Maybe at the end of the day, we will understand that depression is not a disease,” Gratzer said.
“As is often the case with mental health care, these are early days.”