Research concludes that low serotonin does not cause depression. What does that mean for SSRIs?

Since Texas Public Radio:

A UK psychiatrist and researcher led a team that analyzed 17 different reviews, meta-analyses, large individual studies and genetic studies on the low serotonin theory of depression. The research included hundreds of participants, both those diagnosed with depression and those who were not.

The review, published in the journal Molecular Psychiatryis named “The serotonin theory of depression: a systematic overview of the evidence.”, and concludes that nowhere in the years of research reviewed has anyone found evidence that low levels of serotonin in the brain cause depression.

Dr Joanna Moncrieff was the lead author of the review. She explained that his team also examined the literature to determine if any researcher had been able to induce depression in a subject by artificially lowering their serotonin levels. They hadn’t.

What does that mean?

“First, it means that we have no evidence that depressed people have a chemical abnormality in the brain,” Moncrieff explained. “It means that there is no evidence to support the serotonin theory, and that while there are many other theories or speculations about brain abnormalities that may be related to depression, they have not been proven either.”

He added: “So we can’t really say that people who are depressed have some abnormality in the brain.”

Millions of Americans have treated their depression by increasing the level of serotonin in their brains with selective serotonin reuptake inhibitors since Prozac came on the market in 1988. Today’s popular SSRIs include Zoloft, Lexapro, Celexa, and Paxil. If low serotonin in the brain is not the cause of depression, what does that say about using drugs that increase the amount of serotonin in the brain to treat depression?

“We know that antidepressants, for example, produce emotional numbing effects. They numb both negative and positive emotions. And that effect can temporarily nullify or reduce people’s underlying feelings of sadness,” Moncrieff said.

Moncrieff also noted that the evidence that SSRI antidepressants work comes from randomized controlled trials comparing antidepressants and placebo. The difference they found in these trials between antidepressants and placebo is small, she said.

Dr. Jonathan Alpert, president of the Research Council of the American Psychiatric Associationsent TPR a statement responding to the conclusions of the Moncrieff review.

“It is important to separate the issue from the mechanisms, that the review in Molecular Psychiatry focused on the issue of efficacy,” Alpert wrote.

“Regarding mechanisms, the hypothesis that antidepressants work by increasing serotonin and/or the other two monoamine neurotransmitters (dopamine or norepinephrine) was generated in the 1960s based on the best evidence at the time. It was an elegant but overly simplistic hypothesis,” Alpert continued. “Numerous studies over the past few decades have failed to show consistently low serotonin levels in people with depression.”

Alpert added that when it comes to the effectiveness of SSRI drugs, studies have consistently shown that they work better than plebos.

“In some cases they have only modest benefit, but in others they actually save lives,” he wrote. “They remain a very important evidence-based treatment for clinical depression.”

Scientists don’t know how SSRIs work (when they work) to treat depression. Alpert concluded: “The fact that we have consistently learned that antidepressants do not work simply by increasing serotonin…in no way alters the fact that these drugs have worked and continue to work for millions of people whose quality of life and safety are deeply compromised.” “. affected by depression.

Moncrieff disagreed. “I would say two things to that. First of all, whether antidepressants work I would say is debatable because the evidence from randomized controlled trials is very weak. But secondly, I would say that the way antidepressants work or how they have their effects is vitally important,” he said.

Moncrieff hoped his research would change the way people who take SSRIs think about their medications.

“I would encourage people to think hard about what they think drugs are really doing… to realize that these drugs are drugs. They are drugs that modify the normal state of the body and the brain. And I would encourage people to think carefully. Are those changes really useful for me or not?”

But Moncrieff stressed that no one should suddenly stop taking SSRI drugs without talking to their prescribing doctor. The safest way to stop taking an SSRI is to stop slowly, reducing the dose over time under the care of a doctor.

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