Comparing SSRIs
From the public’s perspective, it might appear that SSRIs all act in roughly the same way. But that’s not what Dunham and Venton observed.
Escitalopram, better known by the trade name Lexapro, and paroxetine, better known by the brand name Paxil, increased the brain’s serotonin concentrations at all doses, yet apparently did so much differently.
“Paxil has a faster reuptake compared to Lexapro,” Dunham said. “Paxil binds to the serotonin transmitter with really high affinity, and the concentrations were huge. We think there’s a different molecular mechanism for how it works compared to Lexapro.”
In contrast to these two drugs, citalopram (Celexa) showed relatively lower serotonin concentration increases during the study, despite also slowing reuptake.
Finally, the first-ever SSRI approved in the U.S., fluoxetine (Prozac), did not increase concentrations of serotonin, at least during the limited duration of the study.
“We think Prozac has more of an effect just on reuptake,” Dunham said. “It might be one you have to take it over long periods of time to change the brain chemistry.”
Based on this study alone, she said, it’s not possible to rank the desirability of the drugs. People’s genetics and individual conditions differ. They experience differing levels of improvement on the drugs and, in some cases, suffer differing side effects.
More research is needed, but it’s a start.
Subsequent students in Venton’s lab will test SSRIs against mutations of the serotonin transporter that Dunham and Venton hope will effectively mimic some of the basic genetic variations of humans.
Dunham said the mechanisms of how these and other antidepressant drugs work matter because current prescribing can be hit or miss.
The goal, of course, is to move toward matching each unique patient with the most safe and effective pharmaceutical.
“I hope this research starts a conversation on antidepressant treatments,” she said. “The most common thing is doctors prescribe a drug, and there’s no way to understand what they think works best for the patient. The patient may have to try two or three drugs to find out.”
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How Do SSRIs Like Prozac, Lexapro Really Work? Ask a Fruit Fly - UVA Today
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