One thing almost all psychiatrists can agree on is this: “We need anti-depressants that work more quickly and for more people,” says psychiatry researcher Adam Kaplin.

Indeed, the serotonin selective reuptake inhibitors (SSRIs) that aim to strengthen the brain’s circuits and neurotransmitters normally take seven to 14 days to begin to reduce symptoms. That delay poses an increased risk of suicide for people with treatment-resistant depression, says Kaplin.

Now, after three years of studying how the drug esketamine — a more potent form of ketamine — might relieve symptoms in these patients, Kaplin and his colleagues are hopeful. Kaplin’s research, part of a multisite, international trial, investigated the biological basis of depression and usefulness of intranasal esketamine to treat it. Collectively, across all sites participating in the trial, the response rate was between 53 percent and 69 percent during the first month of treatment.

“What’s really important about this drug is that it’s the first to work for treatment-resistant depression with immediate effect,” he says. “It also appears to reduce suicidal ideation.”

Johns Hopkins will soon begin offering the FDA-approved intranasal treatment to patients with intractable depression (those with at least two failed antidepressant regimens) in a supervised clinic setting. The esketamine will be used alongside an antidepressant.

The reason esketamine is so effective, explains Kaplin, is that it’s delivered not only through a different receptor but also via an ion channel — a much faster route for delivering a signal down the neuron highway of the brain. “It targets dozens of brain connections at once, not just one, and manipulates the neurotransmitter glutamate, which many neurons in the brain use to communicate with each other,” he says.

Ketamine is not without controversy. Classified as a schedule III controlled substance, it’s an analog of phencyclidine (PCP) and became a popular party/club drug, nicknamed “Special K.” But Kaplin is quick to defend its medical use.

He notes that in 1970, the FDA approved ketamine for use as an anesthetic in pediatric and adult surgeries because of its high level of safety and immediate response. Used as a sedative in the recent rescue of 12 young boys and their soccer coach from a flooded cave in Thailand, the drug is listed on the World Health Organization’s list of essential medicines.

“Ketamine has an essential role in surgery,” says Kaplin, “and the findings in our trials in patients with treatment-resistant depression have been encouraging.” In these studies, he notes, the dose is significantly lower than for party/club use or use as an anesthetic.

The esketamine trials also suggest an anti-inflammatory effect, notes Kaplin, who serves as psychiatric consultant for the Johns Hopkins multiple sclerosis and transverse myelitis centers of excellence. “That’s good news for my patients with MS and other autoimmune diseases,” he says, pointing out that 50 percent of patients with MS suffer from depression. Suicide from depression is the third leading cause of death in patients with MS across their life span.

Until now, electroconvulsive therapy (ECT) has offered the best approach for treatment-resistant psychotic depression, notes Kaplin. But ECT is not without side effects. These include confusion, memory loss, nausea and headaches. Ketamine, too, has possible side effects, including mild nausea, dizziness and confusion, but patients are closely observed for at least two hours after treatment to ensure their safety, after which the side effects have subsided.

Seeing the positive effect of esketamine on patients, says Kaplin, “[is] kind of an end goal for us: It’s not perfect, but for patients who don’t respond to other treatments, esketamine can provide immediate relief from despair.”