Experts initially thought that depression must be caused by low levels of neurotransmitters in the brain, in part because the first antidepressant drug — accidentally discovered in the 1950s — increased circulating amounts of the chemicals. Further research suggested that serotonin played an especially important role in mood. This so-called “chemical imbalance” theory gained a foothold in the cultural psyche and was promoted by ads for the medications.
However, starting in the 1990s, researchers began to understand that depression was much more complicated and that serotonin played only a nominal role. For one thing, S.S.R.I.s increase serotonin levels immediately, but it takes several weeks before people start to feel better. Studies also started to emerge showing that another brain system played a role: People with depression consistently have less volume in an area called the hippocampus that’s important for regulating mood.
The current prevailing theory, Dr. Hellerstein said, is that chronic stress can cause the loss of connections — called synapses — between cells in the hippocampus and other parts of the brain, potentially leading to depression. Antidepressants are now thought to work at least in part by helping the brain form new connections between cells. Researchers aren’t exactly sure how increasing serotonin with an S.S.R.I. causes these synapses to regrow. One possibility is that the medications also increase levels of other brain chemicals, called growth factors, that help those connections form and spread.
A paper published earlier this year made headlines for presenting several decades’ worth of evidence that people with depression don’t have less serotonin than people who are not depressed. To most psychiatrists, the paper didn’t reveal anything new, and it didn’t mean antidepressants aren’t effective (a widely held misinterpretation of the paper). Instead it revealed a fundamental disconnect between how the public viewed depression and how the experts thought about it.
Antidepressants Don’t Work the Way Many People Think
The most commonly prescribed medications for depression are somewhat effective — but not because they correct a “chemical imbalance.”