A recent study found inconsistent evidence linking the neurotransmitter serotonin to depression. In an article for The Conversation, the study authors concluded that it is impossible to say whether SSRI antidepressants are worth taking. But is it safe to conclude that serotonin is not involved in depression or that modern antidepressants are not helpful in treating the condition?
Depression is a common and serious life-limiting condition. Low mood and loss of enjoyment are its core symptoms, but many unique symptom combinations can lead to a diagnosis. Two people with depression can have very different symptoms.
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The roots of depression are varied and people can have very different reasons for their symptoms. Psychological trauma is a well-established risk factor. And inflammation is increasingly recognized as a likely cause in many research studies.
Many genetic factors have also been identified, each with a very small effect. There are probably thousands of small genetic effects with each person in an almost unique combination that can increase the risk of depression.
These risk factors explain why some people experience depression more often than others, but people with depression often report multiple risk factors, and it is usually not possible to conclude which, if any, caused their symptoms.
Depression, like many conditions defined primarily by its symptoms, is unlikely to be a single condition with a simple set of discrete causes. Similarly, it is unlikely that there is a single therapy or drug that will treat everyone effectively. But the diverse symptoms and risk factors underlying depression don’t mean we lack effective treatments.
Antidepressants were initially discovered by repurposing a drug used to treat tuberculosis, with little understanding of their effects on the brain.
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Early research revealed that antidepressants increased the amount of serotonin and norepinephrine in the brain. These findings formed the basis of a theory of depression, known as the monoamine hypothesis, which suggests that insufficient levels of these neurotransmitters are an underlying mechanism of depression that can be corrected with antidepressants.
This simplistic explanation of depression and its treatment has met with conflicting data and justified skepticism, and several alternative theories of depression and antidepressants have been proposed.
For more than a decade, few researchers and health professionals would refer to depression as a simple “chemical imbalance.” However, it would be unwise to completely rule out the role of serotonin, as there is still some evidence for its involvement in depression. Although limited access to living human brain tissue means direct confirmation of serotonin’s role in depression is difficult.
Few professionals would refer to depression as a “chemical imbalance” in the brain. r.classen/Shutterstock
Our limited understanding of both depression and antidepressant treatment has led the authors of the aforementioned study to question whether antidepressants are a useful approach to treatment. These criticisms are not new, but they incorrectly imply that an understanding of the mechanism is necessary for effective treatment.
Instead, the cornerstone for identifying effective treatments is the randomized controlled trial (the gold standard of clinical research), which has been widely applied to the study of antidepressants and psychotherapies. This type of study can reliably tell us whether a treatment works or not, even if we have no idea why the treatment is effective.
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Beyond any reasonable doubt
Randomized controlled trials of thousands of depressed people have proven beyond a reasonable doubt that antidepressant drugs are effective in depression. Studies of people with depression treated with antidepressants can also provide important information about how treatments deliver their benefits and may in the future provide important information about why some people respond more than others.
Conditions defined largely by their symptoms are difficult to research and treat, but that hasn’t stopped the development of effective treatments.
Depression is usually effectively managed with antidepressants or talking treatments such as cognitive behavioral therapy, despite an incomplete understanding of the condition and how these treatments work.
We can’t tell if the treatments are treating the underlying problem because we haven’t yet identified what it is. To imply that SSRI antidepressants may not be worth it is to misconstrue an evidence base that says just the opposite.
We are steadily beginning to understand more about the causes of depression and to identify subtypes, or “depressions,” that have more specific mechanisms and treatments.
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Our understanding of depression and its treatment has been advancing for over a century and shows no signs of slowing down. Identifying the causes and new treatments for depression is difficult but essential if we are to tackle one of the most common causes of disability worldwide.
Andrew M McIntosh, Professor of Biological Psychiatry, University of Edinburgh and Cathryn Lewis, Professor of Genetic Epidemiology and Statistics, King’s College London
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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