A Yale-led study may help scientists develop a new class of antidepressant drugs for treatment-resistant patients.
Researchers found that the novel drug lanicemine has antidepressant effects similar to those of the anesthetic ketamine but does not cause the negative psychological effects associated with ketamine. This finding shows that targeting the glutamate system of the brain, which both lanicemine and ketamine do, promises rapid improvement in clinical symptoms for those who failed to respond to traditional treatment. The study was funded by the biopharmaceutical company AstraZeneca and was published in Molecular Psychiatry on Oct. 15.
“Lanicemine can give us confidence that with the right molecule we could get the therapeutic efficacy of a drug like ketamine and mitigate some of the side effects,” said senior study author and AstraZeneca researcher Michael Quirk.
Since the 1980s, studies have indicated that drugs acting on the glutamate system produce antidepressant effects that are in some ways superior to traditional antidepressants that target the brain’s serotonin, norepinephrine and dopamine neurotransmitter systems. In a study performed at Yale in 2000, ketamine was shown to produce significant clinical improvement in treatment-resistant patients in 24 hours. Traditional antidepressants take at least seven weeks to show such improvement, if they do at all.
In this study, researchers examined the effects of lanicemine and ketamine on clinically depressed patients who had not responded to previous treatment. The study found that the patients had a clinical response to lanicemine treatment without the side effects associated with ketamine, such as psychosis and risk of addiction.
Yale professor of psychiatry John Krystal, who was on the research team of the 2000 study on ketamine, said he praises the study for providing new insight into the biology of depression. This new rapid-acting class of drugs may bring great benefit to severely ill or suicidal patients, he added.
Sanjay Mathew, a psychopharmacologist at Baylor College of Medicine, said the study was “very well done.”
Quirk and study lead author and Yale professor of psychiatry Gerard Sanacora both said they see more research as key for further developing antidepressants that target the glutamate system, in part because long-term safety effects have yet to be examined.
“We’ve been learning about [traditional antidepressants] for 50 years now and we still don’t understand everything about them,” Quirk said. “In the next few years to have a complete understanding about a new class of medicines that could be potentially very important is a little optimistic.”
According to Krystal, this research is moving in two important directions. The first is finding a way to translate short-term antidepressant effects as seen in this study into a longer-term treatment to “stave off the return of depression symptoms.” The second “very exciting” direction is rooted in the fact that these antidepressants work so quickly.
According to the National Institute of Mental Health, depression affects approximately 15 million American adults, or 6.7 percent of the adult population, every year.