However, from the 1990s researchers began to understand that depression was much more complicated and that serotonin only played a nominal role. For one thing, SSRIs immediately increase serotonin levels, but it takes several weeks before people start to feel better. Studies have also started to emerge showing that another brain system plays a role: people with depression consistently have less volume in an area called the hippocampus that is important for regulating mood.
According to Dr. Hellerstein, the current prevailing theory is that chronic stress can lead to the loss of connections – called synapses – between cells in the hippocampus and other parts of the brain, which can lead to depression. Antidepressants are now thought to work at least in part by helping the brain make new connections between cells. Researchers don’t know exactly how increasing serotonin with an SSRI causes these synapses to regrow. One possibility is that the drugs also increase levels of other brain chemicals, called growth factors, which help form and spread these connections.
A paper published earlier this year made headlines for presenting decades of evidence that people with depression have no less serotonin than non-depressed people. For most psychiatrists, the article revealed nothing new, and that did not mean that antidepressants weren’t effective (a widely held misinterpretation of the article). Instead, it revealed a fundamental disconnect between how the public perceived depression and how experts thought about it.
“To me, it’s an old depression theory,” said Dr. Daniel Iosifescu, professor of psychiatry at NYU Langone Health. “It was already invalidated 20 years ago, so we’re basically putting the nail in the coffin, so to speak.”
What alternatives to antidepressants are available?
Alternative treatments for depression have emerged that attempt to help the brain make new connections more efficiently, including ketamine and psychedelic therapy (which is not approved by the Food and Drug Administration). These interventions appear to be about as effective as antidepressants, improving depression scores in about 60% of people who try them. More importantly, they are able to treat some of the people who don’t respond to traditional medicines. The drugs are considered riskier and more invasive than antidepressants, however, so they are meant to be used as a last resort, not first-line treatment, Dr. Sanacora said.
Some psychiatrists have also started recommending non-pharmaceutical treatments to help people with depression. Dr Hellerstein said when he assesses a new patient, he now pays more attention to habits, such as sleep, diet and exercise, and often recommends behavioral changes, therapy or meditation. before taking medication. Research suggests that exercise can also help build new connections in the brain, and in some studies exercise has been shown to be as effective as antidepressants in treating depression. Meditation has been shown to help relieve feelings of stress and anxiety, and there is a clear link between sleep deprivation and anxiety in the brain.
“You’re, I think, making a more holistic assessment of that person’s lifestyle than perhaps you did in the late 1980s,” Dr. Hellerstein said.
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