Dutch investigators will soon publish an article in Neurochemistry International that sheds light on how SSRI antidepressants affect the serotonergic system over the longer term, and why abrupt discontinuation of an SSRI can be so problematic. The study also serves as a reminder of how  the public belief that SSRIs “increase” serotonin levels in the brain is belied by science.

In the study, the researchers administered citalopram to the rats for two weeks (there was a control group as well), and then the drug-treated rats were either abruptly withdrawn from the drug or continued on it for another three days. The rats were then sacrificed and their brain tissue analyzed. The investigators likened this dosing regimen to a “long-term treatment paradigm.”

In the drug-maintained rats, serotonin content at the end of 17 days was “reduced by 60% on average in nine areas of the brain,” compared to controls. This depletion appears to be part of a compensatory response to the drug. Since an SSRI blocks the normal reuptake of serotonin from the synaptic cleft, the neurotransmitter stays in this extracellular space longer than normal, and in response, the brain’s synthesis of serotonin dramatically decreases. As a result, serotonin levels in brain tissues end up markedly depleted.