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Key TakeawaysThe so-called “serotonin theory” claims that the activity or levels of serotonin in the brain are responsible for depression.A major review of prior research says there is no convincing evidence to support this theory.Many people take antidepressants because they’ve been led to believe in a biochemical cause for depression, but this review calls into question what antidepressants actually do.

Key Takeaways

The so-called “serotonin theory” claims that the activity or levels of serotonin in the brain are responsible for depression.A major review of prior research says there is no convincing evidence to support this theory.Many people take antidepressants because they’ve been led to believe in a biochemical cause for depression, but this review calls into question what antidepressants actually do.

This idea or hypothesis was the original justification for the use of modern antidepressants (selective serotonin reuptake inhibitors, known asSSRIs) and the pharmaceutical industry heavily promoted it in the 1990s and 2000s, Moncrieff explains. “Many scientists have known that the evidence to support it was weak and contradictory but because no one had done a systematic overview of the evidence before, it was difficult to say whether it was or wasn’t true,” she adds.

Keeping It in PerspectiveWhile the results of this study are certainly significant, it doesn’t negate the effectiveness of antidepressants for many people, nor does it mean you should stop taking them. More research is needed in addition to expanded education around alternative methods for managing depression.

Keeping It in Perspective

While the results of this study are certainly significant, it doesn’t negate the effectiveness of antidepressants for many people, nor does it mean you should stop taking them. More research is needed in addition to expanded education around alternative methods for managing depression.

A Closer Look at the Review

The studies involved in the review included tens of thousands of participants and adopted several different approaches to the relationship between serotonin and depression.

Research comparing levels of serotonin and its breakdown products in the blood or brain fluids did not find a difference between people diagnosed with depression and healthy control (comparison) participants.

Joanna MoncrieffThe current study allows us to come to a proper evidence-based verdict on the serotonin theory of depression, which we believe is important for the scientific community and for the general public.

Joanna Moncrieff

The current study allows us to come to a proper evidence-based verdict on the serotonin theory of depression, which we believe is important for the scientific community and for the general public.

Several large studies looked at gene variation, including the serotonin transporter gene, but they identified no difference in the genes of people with depression and healthy controls.

Many studies considered how stressful life events impact the risk of depression and found that people who had experienced more stressful life events were more likely to have depression.

“The current study allows us to come to a proper evidence-based verdict on the serotonin theory of depression, which we believe is important for the scientific community and for the general public,” Moncrieff says.

What Will the Future of Mental Health Care Bring?

What Does This Mean for Depression Care?

The bottom line is that we can’t say for certain that antidepressants work in the way that most people have been led to believe, says Moncrieff. “That is, they do not correct an underlying serotonin deficiency or abnormality, because the latter has not been demonstrated,” she explains.

Aron Tendler, MD, C.BSM,BrainsWayChief Medical Officer, says that while the recent review challenges the serotonin theory, it doesn’t challenge the efficacy ofmental health treatment.

Aron Tendler, MD, C.BSMThis review reminds all scientists to be humble and focus on the data rather than the theory.

Aron Tendler, MD, C.BSM

This review reminds all scientists to be humble and focus on the data rather than the theory.

“Many psychiatrists and neuroscientists suspected that serotonin theory was invalid from the NIMH-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, which was completed in 2004, or even before that,” Dr. Tendler says.

He points out that this is why there are different classes of antidepressants that work on other neurotransmitters, plus other treatments such as psychotherapy, transcranial magnetic stimulation, andelectroconvulsive therapy.

“This review reminds all scientists to be humble and focus on the data rather than the theory,” Dr. Tendler adds.

Are We Closing the Mental Health Treatment Gap?

A New Understanding of Depression?

Moncrieff hopes that rather than throw yet more money at trying to find the ever elusive chemicalorigins of depression, the medical community will accept that depression is not a biological state but an emotional reaction to difficult life circumstances and past experiences.

“There is strong evidence that adverse life events, such as divorce, poverty, debt, loneliness, child abuse, unemployment, etc, make people more vulnerable to depression,” Moncrieff says. “What this means is that we should stop seeing depression as a medical condition and view it as a human reaction. Of course the brain is involved in depression, as it is involved in all our moods and actions. But that does not mean that we can find the origin of depression in the brain, or even a part of its origin.”

Mental health treatment that is tailored to each individual is key, Moncrieff says, because every case involves a different set of difficult circumstances.

“Things like exercise and psychological therapy may have some general use and have shown to be effective,” she adds.

What This Means For YouIf you’re taking antidepressants and thinking twice about whether you should be, don’t stop them suddenly. Seek advice from your doctor, and if you do decide to stop make sure you do it with medical supervision and support, and reduce your dose very slowly.

What This Means For You

If you’re taking antidepressants and thinking twice about whether you should be, don’t stop them suddenly. Seek advice from your doctor, and if you do decide to stop make sure you do it with medical supervision and support, and reduce your dose very slowly.

As Evidence For Treatment Potential Grows, So Has Psychedelic Legality

1 SourceVerywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA.The serotonin theory of depression: A systematic umbrella review of the evidence.Mol Psychiatry. 2022. doi:10.1038/s41380-022-01661-0Additional ReadingSinyor M, Schaffer A, Levitt A.The sequenced treatment alternatives to relieve depression (STAR*D) trial: A review.Can J Psychiatry. 2010;55(3):126-135. doi:10.1177/070674371005500303

1 Source

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA.The serotonin theory of depression: A systematic umbrella review of the evidence.Mol Psychiatry. 2022. doi:10.1038/s41380-022-01661-0Additional ReadingSinyor M, Schaffer A, Levitt A.The sequenced treatment alternatives to relieve depression (STAR*D) trial: A review.Can J Psychiatry. 2010;55(3):126-135. doi:10.1177/070674371005500303

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA.The serotonin theory of depression: A systematic umbrella review of the evidence.Mol Psychiatry. 2022. doi:10.1038/s41380-022-01661-0

Sinyor M, Schaffer A, Levitt A.The sequenced treatment alternatives to relieve depression (STAR*D) trial: A review.Can J Psychiatry. 2010;55(3):126-135. doi:10.1177/070674371005500303

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