Scientists May Be on the Road to Making Antidepressants Work Faster

Waiting six weeks for antidepressants to kick in can be excruciating for someone who's really suffering, but science may have a solution.

depressedMonkey Business Images/ShutterstockIf you’ve spotted the warning signs of depression, your doctor might prescribe antidepressants, the first line of defense for many people with mental health issues. But the drugs certainly aren’t a quick fix—it can take up to six weeks for the most commonly prescribed antidepressants to start working.

Most people with depression are prescribed selective serotonin reuptake inhibitors (SSRIs), such as Prozac and Zoloft. These drugs work by blocking the absorption of serotonin, based on the belief that depression is caused by a shortage of the neurotransmitter serotonin.

Although doctors have been prescribing SSRIs for depression for decades (Fluoxetine was FDA approved in 1987 and is thought to be the first SSRI to be marketed) exactly how they work has remained something of a mystery. It’s also never been clear why it can take several weeks or even months for patients to feel the behavioral effects of the drugs. (Here are things about depression psychologists wish people knew.)

In trying to answer these questions, new research published in the journal Neuron has developed some helpful insights. Working together, Paul Greengard’s lab at Rockefeller University in New York and Adrien Peyrache, a researcher at the Montreal Neurological Institute and Hospital of McGill University, found that acute and chronic treatment with SSRIs had very different outcomes. Serotonin activates different receptors depending on the length of treatment, and long-term treatment reorganizes neural activity, while short-term treatment does not. This may explain why SSRIs take a long time to have a psychological effect, despite some fast physiological responses.

Faster-acting antidepressant drugs might not be out of the realm of possibility. Greengard’s lab previously established that a protein called p11 plays a key role in depression-like behaviors. This protein is strongly expressed in a class of cells called the cholecystokinin (CCK) cells, which are in the hippocampus. The CCK neurons are instrumental in balancing the excitation and inhibition (the turning on and off) of the network, and they have a much higher number of receptors for serotonin than the other neurons of the hippocampus. The researchers found that serotonin normally inhibits CCK neurons, leading to well-balanced activity in the hippocampus. Artificially inhibiting CCK results in the same anti-depressant effects of SSRIs, suggesting that these cells may be key in the advancement of fast-acting antidepressant medications.

“We’ve uncovered an important aspect of how these drugs alleviate depressive symptoms, yet much work still needs to be done,” Peyrache told EurekAlert. “By untangling some of the processes at the heart of the mechanisms, we are hoping to open avenues for future treatments that will focus more on the specific brain area and cell class involved, rather than a broad, pan-neuronal action. More targeted drugs also often have fewer and less severe side effects.”

Remember, not every antidepressant works for everyone. Here’s what to do when your antidepressants aren’t working.

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