Studies show that low serotonin does not cause depression. What does this mean for SSRIs?

From Texas Public Radio:

A psychiatrist and researcher from the United Kingdom led a panel that analyzed 17 different reviews, meta-analyses, large single studies and genetic studies of the low serotonin depression theory. The study involved hundreds of participants, both diagnosed with depression and those without it.

Review published in the journal Molecular Psychiatryis called “The Serotonin Theory of Depression: A Systematic Umbrella Review of 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 her team also reviewed the literature to determine if any researcher was able to induce depression in a subject by artificially lowering serotonin levels. They didn’t have.

What does this mean?

“First of all, this means that we have no evidence that people with depression have a chemical abnormality in the brain,” Moncrieff explained. “This means that there is no evidence to support the serotonin theory, and that while there are many other theories or suggestions about brain abnormalities that may be associated with depression, they have not been demonstrated either.”

She added, “So we really can’t say that people who are depressed have any abnormalities in their brains.”

Millions of Americans have been treating depression by increasing brain serotonin levels with selective serotonin reuptake inhibitors since Prozac hit the market in 1988. Currently popular SSRIs include Zoloft, Lexapro, Celexa, and Paxil. If low brain serotonin levels are not the cause of depression, what does this say about the use of drugs that increase brain serotonin levels to treat depression?

“We know that antidepressants, for example, cause emotional numbness. They dull both negative and positive emotions. And this effect can temporarily suppress or reduce people’s underlying feelings of sadness,” Moncrieff said.

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

Dr. Jonathan Alpert, chairman of the American Psychiatric Association’s Research Council, sent a statement to TPR responding to the findings of Moncrieff’s review.

“It is important to separate the question of mechanisms—which is reviewed in Molecular Psychiatry focused – in terms of efficiency,” Alpert wrote.

“In terms of mechanisms, the hypothesis that antidepressants work by increasing levels of serotonin and/or two other monoamine neurotransmitters (dopamine or norepinephrine) was put forward in the 1960s based on the best data of the time. It was an elegant hypothesis, but too simplistic,” continued Alpert. “Multiple studies over the past decades have failed to show consistently low levels of serotonin in people with depression.”

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

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

Scientists don’t know how SSRIs work – if they really work – in treating depression. Alpert concluded: “The fact that we keep learning that antidepressants don’t work simply by increasing serotonin…doesn’t change in any way the fact that these medications have worked and continue to work for millions of people whose quality of life and safety has been greatly reduced.” . suffering from depression.”

Moncrieff was indignant. “I would say two things about that. First, I would say it’s debatable whether antidepressants work because the evidence from randomized controlled trials is very weak. But secondly, I would say that how antidepressants work or how they work is critical,” she said.

Moncrieff hoped her study would change how people taking SSRIs feel about their medications.

“I would encourage people to think hard about what they think drugs actually achieve… to understand that these drugs are drugs. These are drugs that change the normal state of the body and brain. And I encourage people to think carefully. Are these changes really beneficial for me or not?

But Moncrieff emphasized that no one should suddenly stop taking SSRIs without consulting their doctor. The safest way to stop taking SSRIs is to do so slowly, decreasing the dose over time under the supervision of a doctor.

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