Depression isn’t Caused by Low Serotonin Level, Are SSRIs still Effective?

The cause of depression is known to be influenced by serotonin levels that are lower than needed. For this reason, people with depression are often recommended to take Selective Serotonin Reuptake Inhibitors (SSRIs), the most popular antidepressant drugs.

Several previous studies have concluded that SSRIs can significantly reduce the risk of depression. However, a recent study refutes this.

A new study from a team of British, Swiss and Italian scientists evaluated the evidence for whether depression is associated with serotonin activity. They questioned the use of antidepressants and the serotonin theory of depression.

So far, the theory we knew is that depression is the result of an imbalance in brain chemicals, especially serotonin. This theory was influential for decades and provided important justification for the use of antidepressants.

The decreased levels of serotonin were first linked to depression in the 1960s. This theory was widely accepted in the 1990s with the advent of Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants, which can temporarily increase the availability of serotonin in the brain.

Serotonin is a chemical courier that carries signals between nerve cells in the brain. It’s thought to have a good influence on mood, emotion and sleep.

NHS said SSRIs are the most commonly prescribed type of antidepressant. They are generally better than other antidepressants because they have fewer side effects. Although people may have the side effects, it is only troublesome at first, but they usually get better by the time. It’s also safe to use during pregnancy.

Fluoxetine is probably the most popular SSRI (sold under the brand name Prozac). Other SSRIs include citalopram (Cipramil), escitalopram (Cipralex), paroxetine (Seroxat), and sertraline (Lustral).

One in six adults in the UK and 13 percent of Americans take antidepressants. Surveys show that 80 percent or more of the general public now believe that depression is caused by an imbalance of brain chemistry.

The latest study, published in Molecular Psychiatry on July 20, 2022, analyzed 17 previous studies starting from 2010 on serotonin levels in people with depression.

In the study, Professor Moncrieff and colleagues aimed to capture all the relevant studies that have been published in the most important research areas on serotonin and depression. The studies included in this review involved tens of thousands of participants.

As a result, there was no evidence that depressed people had lower serotonin levels or abnormal serotonin activity compared to non-depressed people.

“It’s always hard to prove anything negative, but I think we can say that from the many studies done over the decades, there is no convincing evidence that depression is caused by a serotonin disorder, particularly by lower levels or decreased serotonin activity,” says Dr. lead author of the study, Joanna Moncrieff, a professor of psychiatry at University College London and a consultant psychiatrist at the North East London NHS Foundation Trust (NELFT).

The study doesn’t necessarily label SSRI use as ineffective but suggests that SSRIs don’t treat depression by improving serotonin levels. They found no difference in serotonin levels between people diagnosed with depression and healthy people, although polls show that 95 percent of the public believes this. Lowering serotonin levels in healthy volunteers also did not lead them to develop depression.

Is SSRI Still Effective?

However, many experts in this field have different opinions. They agreed that depression is a heterogeneous disorder with potentially multiple underlying causes. It’s not like a simple disease with just one direct cause.

Allan Young, director of the centre for affective disorders at the Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, said that depression is not only because of imbalance theory, it’s related to biopsychosocial model.

“Many of us know that taking paracetamol can help with headaches and I don’t think anyone would believe that headaches are caused by not having enough paracetamol in the brain, the same logic applies to depression and drugs used to treat depression” — Michael Bloomfield

Michael Bloomfield, a psychiatrist at University College London said there is consistent evidence that antidepressant medicines can be helpful in the treatment of depression and can be life-saving.

Many other experts agreed that antidepressant medicines are one type of treatment alongside other types of treatment like psychotherapy (talking therapy). Taking SSRIs can still help treat depression, although it may not get to the root of the problem.

The effectiveness of antidepressant medication is different for each individual. That’s why it’s important that patient care is based on each individual’s needs and reviewed regularly.

Every medicine, including SSRIs which have been used for patients is based clinical trial evidence. This review does not change that.

We would not recommend for anyone to stop taking their antidepressants based on this review, and encourage anyone with concerns about their medication to contact their GP.


Medika Life has provided this material for your information. It is not intended to substitute for the medical expertise and advice of your health care provider(s). We encourage you to discuss any decisions about treatment or care with your health care provider. The mention of any product, service, or therapy is not an endorsement by Medika Life

Isabella Soerjanto MD
Isabella Soerjanto MD
Isabella is a medical doctor, living in Bali, Indonesia. She is an empathetic and compassionate general practitioner with a lively and energetic character. She is eager to put all of her knowledge and skills to use and be of service to patients and the hospital. She is passionate about writing, medical humanities & education, and adventures.
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