VA Panel Puts Limits on Use of Drug
PHILADELPHIA—Is esketamine a revolutionary treatment for depression or just another moderately effective adjunctive medication with some potentially serious risks? The VA’s Medical Advisory Panel leaned toward the latter position when it decided in June to approve the use of esketamine on a nonformulary basis for individuals who have previously failed at least two trials of other antidepressants.
The formulary committee’s decision has done little to tamp down debate about the drug, however.
That esketamine is the first medication in a new drug class approved for treatment of depression in three decades remains undisputed. N-methyl-D-aspartate receptor antagonists, esketamine and its parent drug, ketamine, stimulate glutamate production, which in turn triggers development of new neural connections, according to Gerard Sanacora, MD, PhD, a psychiatrist at Yale Medicine and ketamine researcher.1
Glutamate is far more prevalent in the brain than the neurotransmitters targeted by most current antidepressants, serotonin and norepinephrine. Its central role in neuronal excitation means it significantly impacts critical brain functions, including cognition, emotions, sensory perception and motor coordination. Esketamine and ketamine’s ability to act on a molecule with such a broad portfolio and prevalence might explain their ability to relieve depression in some of the 30% of people with major depression who have not responded to other therapies.
That same broad impact on the brain has made ketamine an effective anesthetic for decades and a powerful painkiller used by battlefield medics. It also drives ketamine’s abuse as a hallucinogenic—and much of the debate on the safety of esketamine, the s-enantiomer of ketamine.
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