62 DISCOVERMAGAZINE.COMA Paradigm Shift for
Depression Treatment
BY LINDA MARSAi
The tens of millions of people who have severe depression
have had few treatment options — until now. In March, the
U.S. Food and Drug Administration approved esketamine
(Spravato), a fast-acting nasal spray derived from ketamine that is the
first genuine advance in treating depression in more than 30 years.
First synthesized in the 1960s and still used globally as an anes-
thetic on battlefields and in surgery, ketamine became popular as
an illicit club drug known as Special K in the 1980s and ’90s because
it triggered trippy dissociative side effects. But nearly two decades
ago, researchers noticed it banished depression even in people who
are suicidal or resistant to treatment. Another plus: Their response
was swift and profound.
Traditional antidepressants, such as selective serotonin reup-
take inhibitors (SSRIs), can take months to work, and about 30
percent of people who are prescribed them don’t get much benefit.
With ketamine, though, relief is almost instantaneous — usually
within a few hours — and the effects can last for a week or more.“Initially, we were shocked, but it was also extremely exciting,”
says John Krystal, one of the pioneers in ketamine research and
chief of psychiatry at Yale Medicine, of his early work in the ’90s
on establishing the drug as a potential treatment.
While SSRIs activate serotonin, a chemical messenger impor-
tant in the function of brain circuitry, ketamine triggers a gush
of the neurotransmitter glutamate, which activates the brain’s
main information highway. “Ketamine rapidly awakens dormant
neural machinery and enhances neural connections,” says Carlos
Zarate Jr., chief of mood disorders research at the National Institute
of Mental Health.
The drug’s approval will not only help millions but also deepen
our understanding of depression’s underlying mechanisms, paving
the way for even more effective therapies. (Pilot studies suggest ket-
amine may also combat bipolar disorder and post-traumatic stress
disorder.) It may be “a transformative treatment,” says Krystal.
“Patients feel ketamine gave them their life back.” SH
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