Why Antidepressants May Not Work

In July of 2022, Professor Joanna Moncrieff with psychiatrists at UCL published in the journal Molecular Psychiatry saying "after a vast amount of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities."

Most antidepressant medications are selective serotonin reuptake inhibitors (SSRIs) which are specifically to correct low serotonin levels. But this research concludes that adjusting serotonin levels may have no effect on depression levels.

The research team compared seratonin levels in blood and brain fluid and found no difference between those diagnosed with depression versus those who were healthy control group participants.

The report also cites prior research where serotonin levels were lowered in some patients but not others, and no link to depression was found.

Additional studies were cited where the genes of tens of thousands of patients were examined for the serotonin transporter, and there was no difference discovered between those with or without depression.

The authors suggest antidepressants may produce short term increased serotonin levels and changes in the brain, but in fact, long term usage actually lowers serotonin levels in the blood. Meaning even if serotonin was responsible for depression, long term SSRI use wouldn't help.

"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." - Professor Moncrieff

"I had been taught that depression was caused by low serotonin in my psychiatry training and had even taught this to students... Being involved in this research was eye-opening...everything I thought I knew has been flipped upside down." - Co-author Dr Mark Horowitz

It seems that adverse life events and low mood as a result of them may be more at play that once thought. Depression may not be as easy to cure as simply adjusting the levels of a specific brain chemicals.

Bottom line: Despite 85-90% of the public believing depression is caused by low levels or serotonin or a chemical imbalance, growing research shows this may be an over-simplification. Antidepressants nearly all adjust serotonin levels, but may not work due to this mistaken cause.