SSRI, depression
The common belief that depression is linked to low levels of the neurotransmitter serotonin is again being questioned by top psychiatrists.

Professor David Healy of the Hergest Unit, Bangor, U.K., writes in the British Medical Journal that the idea that serotonin levels might be lower in people with depression was rejected in the 1960s. But when serotonin reuptake inhibiting (SSRI) drugs were developed in the 1980s, the manufacturers searched for a problem the drugs could solve.

So drug companies attempted marketing SSRIs for depression, Healy writes, even though they were less effective than older tricyclic antidepressants, and "sold the idea that depression was the deeper illness behind the superficial manifestations of anxiety."

"The approach was an astonishing success, central to which was the notion that SSRIs restored serotonin levels to normal, a notion that later transmuted into the idea that they remedied a chemical imbalance," he writes.

But "[N]o one knew if SSRIs raised or lowered serotonin levels; they still don't know," he states. "There was no evidence that treatment corrected anything."

Healy says the "lowered serotonin" story took root in the public domain rather than in psychopharmacology. The "myth" then extended to the complementary health market.

For many years now, depressed individuals have been encouraged to eat foods or engage in activities that will raise their serotonin levels. For doctors, "it provided an easy shorthand for communication with patients," he writes.

"For patients, the idea of correcting an abnormality has a moral force that can be expected to overcome the scruples some might have had about taking a tranquilizer, especially when packaged in the appealing form that distress is not a weakness."

Healy said many books and articles expound such theories because of a misconception that lowered serotonin levels in depression are an established fact, and "A]bove all the myth co-opted doctors and patients, meanwhile more effective and less costly treatments were marginalized."

He concludes that serotonin "is not irrelevant," but that this story "raises a question about the weight doctors and others put on biological and epidemiological plausibility." Clinical trial data that show no evidence of efficacy must not be put aside, he urges, to make way for a plausible (but mythical) account of biology and treatment.

"The emerging sciences of the brain offer enormous scope to deploy any amount of neurobabble. We need to understand the language we use. Until then, so long, and thanks for all the serotonin," he concludes.

Some of the most commonly prescribed antidepressant medications, including Prozac (fluoxetine), Paxil (paroxetine), and Zoloft (sertraline), are SSRIs, blocking the reabsorption of serotonin into brain cells in order to raise levels of the neurotransmitter in the brain.

But some evidence suggests people who are depressed actually have higher levels of serotonin in their brains, not lower. This means that SSRIs could actually be exacerbating the situation. This may explain why patients often report feeling worse, not better, for their first two weeks on antidepressants.

In a separate recent article, Paul W. Andrews, Ph.D., of McMaster University in Canada, and colleagues aver that the likely evolved function of the serotonergic system is energy regulation.

"The role of serotonin in depression and antidepressant treatment remains unresolved despite decades of research," they state in the journal Neuroscience & Biobehavioral Reviews.

They claim that the research indicates an elevation of serotonin in many types of depression. The higher levels of serotonin during depressive episodes help focus people's minds on conscious thought, to look for a way out of the problem, they believe.

Given that, in their opinion, the serotonergic system evolved to regulate energy, it follows that by increasing serotonin, SSRIs "disrupt energy homeostasis and often worsen symptoms during acute treatment." They go on to state that "symptom reduction is not achieved by the direct pharmacological properties of SSRIs, but by the brain's compensatory responses that attempt to restore energy homeostasis."

Findings from animal studies of melancholia and acute and chronic SSRI treatment support these claims, they write. Furthermore, other neurotransmitters such as norepinephrine and dopamine have also been the target of pharmacological agents designed to modulate their levels, despite a lack of biological measurements for these substances in the brain.

Andrews believes further research is urgent for a clear understanding of the role of serotonin and other neurotransmitter levels in depression. However, it is important that individuals taking SSRIs, or other antidepressants, follow the advice of their physician before making any changes to their medication.


Healy, D. Editorial: Serotonin and depression. BMJ, 22 April 2015, doi: 10.1136/bmj.h1771

Andrews, P. W. et al. Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response. Neuroscience & Biobehavioral Reviews, Volume 51, April 2015, Pages 164-88 doi:10.1016/j.neubiorev.2015.01.018