WHY DO ANTIDEPRESSANTS TAKE SO LONG TO KICK IN?

Quick review of some of the biology behind depression, as scientists understand it: Depressed people are short on a chemical messenger called serotonin. The most popular type of antidepressant (the SSRI) blocks serotonin from reabsorbing into brain cells, leaving more of it hanging around to do its job: boost your mood.

Minutes after you swallow your SSRI pill, the drug bonds to its
targets. But patients don’t see the expected mood boost until weeks or even months later.

Scientists have been trying to understand the delay for a long time, and this week I read some good news: There’s been a breakthrough.

The surprising thing is that it has nothing to do with serotonin. A team of researchers at the University of Illinois at Chicago have been studying a different signaling molecule called the G protein. In previous research they’ve found that in depressed people, these proteins tend to get stuck in a fatty part of the cell membrane called the lipid raft. While stranded there, the G proteins can’t signal. The researchers suggest this diminished signaling could explain the numb feeling people with depression experience.

The team took rat brain cells and bathed them in SSRIs. Over time, they saw the drug build up in the lipid raft area, and as that happened fewer G proteins stuck around. They escaped to areas where they could better do their signaling.

So that’s it, they concluded. That’s why antidepressants are taking so long to work: They’ve got to build up in the cell membrane enough to send the G proteins on their way.

Here’s the part you really care about: Understanding this should lead to better antidepressants. There’s more research to do, but eventually SSRIs will work to speed up that G protein migration, hopefully leading to quicker effects.

This is definitely a topic I’ll be keeping an eye on. I’ll keep you posted!

Satu Woodland is owner and clinician of Mental Health Solutions, an integrative mental health practice located at Bown Crossing in Boise, Idaho. She sees children, adolescents, and adults.