For people with TRD, researchers would need to discover something new. But while monoaminergic antidepressants were the treatment of choice, they didn’t work for everyone, and by the 1990s, development and improvement in the field had slowed. First introduced in the 1950s, these medications increase the activity of the brain’s serotonin, norepinephrine, and dopamine neurotransmitters. Because of this, and a lack of a patent, there was little financial incentive to invest into further research, he wrote.įor depression treatment in the 1970s, monoaminergic antidepressants were the gold standard. Given that, at the time, psychedelic drugs were all the rage, Zarate ventured that ketamine’s potential for abuse “undermined its psychiatric utility.” While traces of early research hinted of ketamine’s potential as an antidepressant, it was deemed too risky and challenging for use in clinical settings at the time. The reasons for this long gap aren’t entirely clear-a mystery Zarate acknowledged in a 2019 paper. But researchers didn’t start connecting the dots until the 2000s. Food and Drug Administration (FDA) in 1970, clues to ketamine’s potential use for depression soon followed. Despite its dissociative properties-side effects that would later haunt ketamine-it proved a reliable anesthetic. While the drug showed promise in early human testing, it gave many people spacy, out-of-body-like experiences. Road to discoveryīorn out of the need for a better anesthetic, researchers created ketamine in 1962. Zarate and other researchers to help people like Michelle, the solution-in an anesthetic known as ketamine-would take more than half a century to uncover. While advances through NIMH-supported research would allow Dr. Zarate said can last decades, and one that places some people with the illness at risk for suicide. TRD affects millions -and for those fortunate enough to find a treatment that works- up to 80% will relapse. “I didn’t think I’d ever feel okay again.” “I felt extremely hopeless and just empty,” she said. When the drugs failed, she repeated this process-each time hoping this could be the one. Like others with TRD, Michelle would take a new medication and wait, enduring the often-considerable side effects, sometimes for more than a month. “I lost interest in everything, including my friends, family, and hobbies-even the blue sky and the sun,” Michelle said. The illness is a persistent and debilitating form of major depressive disorder that doesn’t improve after trying at least two antidepressants. They were people like Michelle, who developed treatment-resistant depression (TRD) after the death of her oldest son. All he knew was that there were still people who needed help. When he arrived at the National Institute of Mental Health (NIMH) in 2001, Carlos Zarate, M.D., had no idea he would take part in discovering a new treatment for an illness that-by definition-defies treatment. Researchers continue to look for ways to deliver the treatment to patients who need it.
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