How well do antidepressants work and what are the alternatives?
However, starting in the 1990s, researchers began to realize that depression much more complicated and that serotonin played only a nominal role. First, SSRIs increase serotonin levels immediately, but it takes several weeks before people start to feel better. Studies are also beginning to emerge showing that another brain system played a role: People with depression constantly have smaller volume in an area called the hippocampus, which is important for mood regulation.
The the current prevailing theoryHellerstein said chronic stress can cause a loss of connections — called synapses — between cells in the hippocampus and other parts of the brain, potentially leading to depression. Antidepressants are 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 SSRIs causes these synapses to regrow. One of the possibilities is that medicines increase levels of other chemicals in the braincalled growth factors, which help these bonds form and expand.
Paper published earlier this year, made headlines for presenting decades of evidence that people with depression have less serotonin than people who are not depressed. To most psychiatrists, this work did not reveal anything new and did not mean that antidepressants are not effective (a widespread misinterpretation of the work). Instead, he found a fundamental disconnect between how the public views depression and what experts think about it.
“To me, it’s an old theory for depression,” said Daniel Iosifescu, MD, a professor of psychiatry at NYU Langone Health. “That was already overturned 20 years ago, so we’re just 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—most notably ketamine and psychedelic therapy (not approved by the Food and Drug Administration). It seems to be about these interventions as effective as antidepressants, improving depression scores in roughly 60 percent of people who try them. More significantly, they are able to heal some of the people which do not fit to traditional medicines. The drugs are considered riskier and more invasive than antidepressants, however, so they’re meant to be used as a last resort rather than a first-line treatment, said Dr. Sanacora.
Some psychiatrists have also begun recommending non-pharmaceutical treatments to help people with depression. dr. Hellerstein said that when evaluating a new patient, he now pays more attention to habits, such as sleep, diet and exercise, and would often recommend behavioral changes, therapy or meditation before medication. There is research to suggest that exercise can also help new connections grow in the brainand in some studies it has been shown that exercise as effective as antidepressants in the treatment of depression. Meditation has been found to help feelings of stress and anxietyand there is a clear connection between lack of sleep and anxiety in the brain.
“I think you’re making a more holistic assessment of the person’s lifestyle than you might have done in the late 1980s,” said Dr. Hellerstein.
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