GoKawiilEvery year, millions of people start taking a drug with therapeutic effects that can’t be fully explained, for a condition that can’t be objectively diagnosed with a laboratory test. Selective serotonin reuptake inhibitors, or SSRIs, are among the most prescribed medications in the world. Yet, even after decades of use, scientists are still untangling the biological changes that SSRIs trigger in the brain and body.
Three mental-health claims from RFK’s wellness movement: what scientists say
“We fundamentally don’t know how they work,” says Maurizio Fava, a psychiatrist at Massachusetts General Hospital in Boston.
That uncertainty collided with politics earlier this year when, speaking at a wellness summit focused on mental health, US Secretary of Health Robert F. Kennedy Jr argued that the drugs are greatly overused and have withdrawal risks that are on a par with heroin. His claims prompted an outcry from some scientists and clinicians, who warned that Kennedy had overstated the concern, potentially scaring people away from life-saving treatment. But others said he had identified a real problem, even if clumsily. “This is a major public-health issue,” says Mark Horowitz, a psychiatrist at Adelaide University in Australia. “I hope the messenger’s controversialness doesn’t kill the message.”
The divide reflects how much remains unresolved with regards to SSRIs. Researchers are still piecing together a complicated picture of the drugs’ therapeutic actions, involving neural circuits and their connecting synapses, gene expression, inflammation, stress hormones and psychological expectation. None yet offers a complete explanation. And the chain of biological changes that ultimately relieves symptoms can look very different from one person to the next. “There’s not one route to depression,” says Catherine Harmer, a cognitive neuroscientist at the University of Oxford, UK.
But many scientists say the field is entering a more revealing era, as new tools begin to connect symptoms to biological processes. “We’re at an inflection point,” says Mark Rapaport, a psychiatrist at Stanford University in California and president of the American Psychiatric Association. He likens it to cancer research in the 1990s, when advances in molecular biology and basic science were leading to the development of the first targeted therapies.
Even many people who are critical of Kennedy’s claims acknowledge that SSRI withdrawal can be a substantial issue for some people. With an estimated one in six adults in the United States taking an antidepressant, even a small proportion experiencing serious problems while discontinuing the drugs amounts to a large public-health concern. “It’s a real phenomenon,” says Fava.
Before scientists can explain fully why withdrawal symptoms occur — or how best to prevent or treat them — they need to finish answering more basic questions: what is happening in the brain when someone is depressed? And what, exactly, are SSRIs doing to change it?
A difficult diagnosis
There is no standard blood test for depression. No genetic screen or brain scan can confirm a diagnosis. Instead, clinicians rely on what people report and how they are functioning in aspects such as sleep, appetite, mood and interest in daily life. “It’s entirely subjective,” says Manish Jha, a neuroscientist at the University of Texas Southwestern Medical Center in Dallas.
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