About time: More scientists are challenging low-serotonin theory of depression

A new paper challenges the prevailing opinion that depression is related to low levels of serotonin in the gaps between nerve cells in the brain.

This theory has predominated for nearly 50 years and has led to the development of the commonly prescribed anti-depressant medications called selective serotonin re-uptake inhibitors, or SSRIs. But it has never been proven.

The science behind many anti-depressant medications appears to be backwards, say the authors of a paper posted by the journal .

SSRIs keep the neurotransmitter's (serotonin) levels high by blocking its re-absorption into the cells that release it.

But those serotonin-boosting medications actually make it harder for patients to recover, especially in the short term, said lead author Paul Andrews, an assistant professor of psychology, neuroscience & behavior at McMaster University in Canada.

"It's time we rethink what we are doing," Andrews says. "We are taking people who are suffering from the most common forms of depression, and instead of helping them, it appears we are putting an obstacle in their path to recovery."

When depressed patients on SSRI medication do show improvement, it appears that their brains are actually overcoming the effects of antidepressant medications, rather than being assisted directly by them. Instead of helping, the medications appear to be interfering with the brain's own mechanisms of recovery.

"We've seen that people report feeling worse, not better, for their first two weeks on antidepressants," Andrews says. "This could explain why."

It is currently impossible to measure exactly how the brain is releasing and using serotonin, the researchers write, because there is no safe way to measure it in a living human brain.

Instead, scientists must rely on measuring evidence about levels of serotonin that the brain has already metabolized, and by extrapolating from studies using animals.

The best available evidence appears to show that there is more serotonin being released and used during depressive episodes, not less, the authors say.

The new paper suggests that serotonin helps the brain adapt to depression by re-allocating its resources, giving more to conscious thought and less to areas such as growth, development, reproduction, immune function, and the stress response.

Andrews, an evolutionary psychologist, has argued in previous research that antidepressants leave patients in worse shape after they stop using them, and that most forms of depression, though painful, are natural and beneficial adaptations to stress.