Depression / Serotonin updated...

 

A group of scientists have said a review which concluded there was no consistent evidence of a relationship between serotonin and depression was biased and seriously flawed.

Last July a systematic umbrella review, published in Molecular Psychiatry, concluded “there is no convincing evidence that depression is associated with or caused by lower serotonin concentrations or activity” and questioned the reasons behind high prescribing rates of antidepressants.

Writing in the same journal, 36 researchers have criticised the paper saying there were 

_methodological weaknesses in the review process, 

_selective reporting of data,

_oversimplification, and 

_errors in the interpretation of neuropsychopharmacological findings.

Lead author of the comment piece, Sameer Jauhar, senior clinical lecturer in affective disorders and psychosis at the Institute of Psychiatry, Psychology, and Neuroscience (IoPPN) at King’s College London, said the authors “presented no new analyses of the data, used their own criteria for assessing research quality, interpreted findings differently from the …

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How most medicines work their magic is understood. But for some it remains a mystery. Among the most mysterious are a group of widely used antidepressants called selective serotonin reuptake inhibitors, the best-known of which is Prozac. 

The Economist July 21.2022

After decades of study, there remains no clear evidence that serotonin levels or serotonin activity are responsible for depression, according to a major review of prior research led by UCL scientists.

The new umbrella review -- an overview of existing meta-analyses and systematic reviews -- published in Molecular Psychiatry, suggests that depression is not likely caused by a chemical imbalance, and calls into question what antidepressants do. 

Most antidepressants are selective serotonin reuptake inhibitors (SSRIs), which were originally said to work by correcting abnormally low serotonin levels. There is no other accepted pharmacological mechanism by which antidepressants affect the symptoms of depression.

Lead author Professor Joanna Moncrieff, a Professor of Psychiatry at UCL and a consultant psychiatrist at North East London NHS Foundation Trust (NELFT), said: "It is always difficult to prove a negative, but I think we can safely say that after a vast amount of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities, particularly by lower levels or reduced activity of serotonin.

"The popularity of the 'chemical imbalance' theory of depression has coincided with a huge increase in the use of antidepressants. Prescriptions for antidepressants have risen dramatically since the 1990s, with one in six adults in England and 2% of teenagers now being prescribed an antidepressant in a given year.

"Many people take antidepressants because they have been led to believe their depression has a biochemical cause, but this new research suggests this belief is not grounded in evidence."

The umbrella review aimed to capture all relevant studies that have been published in the most important fields of research on serotonin and depression. The studies included in the review involved tens of thousands of participants.

Research that compared 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.

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Professor Moncrieff said: "Our view is that patients should not be told that depression is caused by low serotonin or by a chemical imbalance, and they should not be led to believe that antidepressants work by targeting these unproven abnormalities. We do not understand what antidepressants are doing to the brain exactly, and giving people this sort of misinformation prevents them from making an informed decision about whether to take antidepressants or not."

Co-author Dr Mark Horowitz, a training psychiatrist and Clinical Research Fellow in Psychiatry at UCL and NELFT, said: "I had been taught that depression was caused by low serotonin in my psychiatry training and had even taught this to students in my own lectures. Being involved in this research was eye-opening and feels like everything I thought I knew has been flipped upside down.

"One interesting aspect in the studies we examined was how strong an effect adverse life events played in depression, suggesting low mood is a response to people's lives and cannot be boiled down to a simple chemical equation."

Professor Moncrieff added: "Thousands of people suffer from side effects of antidepressants, including the severe withdrawal effects that can occur when people try to stop them, yet prescription rates continue to rise. We believe this situation has been driven partly by the false belief that depression is due to a chemical imbalance. It is high time to inform the public that this belief is not grounded in science."

The researchers caution that anyone considering withdrawing from antidepressants should seek the advice of a health professional, given the risk of adverse effects following withdrawal. 

Professor Moncrieff and Dr Horowitz are conducting ongoing research into how best to gradually stop taking antidepressants.