The U.S. Food and Drug Administration on Tuesday approved the nasal spray medication esketamine — a relative of the club drug and anesthetic ketamine — for use against severe depression.
Sold as Spravato, the fast-acting drug becomes the first new type of medicine approved in years against an illness that plagues millions of Americans.
In a statement, the FDA said Spravato should be used in conjunction with an antidepressant pill and is meant only for people whose depression has not responded to at least two other antidepressants.
Spravato — a much less potent relative of the illicit club drug "Special K" — comes with other restrictions, the FDA said. Ketamine can induce dissociation (feeling disconnected from one's surroundings) and sedation.
Because Spravato might act similarly for a minority of patients, the FDA said safeguards are warranted.
"Because of safety concerns, the drug will only be available through a restricted distribution system and it must be administered in a certified medical office where the health care provider can monitor the patient," said Dr. Tiffany Farchione. She's acting director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research.
Patients will self-administer the nasal spray during visits to a medical clinic, and the spray cannot be taken home. A health care provider will monitor the patient until it is clear that he or she is ready to leave.
Ketamine came first
Approval of a medicine like Spravato is welcome news for patients like Jen Godfrey, who said she couldn't shake the "deep cloud" of depression that lingered even after she found an antidepressant she could tolerate. She turned to clinics that were dispensing the anesthetic ketamine "off-label" for help against depression.
A number of stressors had hit Godfrey hard — five years of fertility treatment and an 80-pound weight gain during pregnancy that left her with persistent pain; a close relative's suicide; another who went missing; and her own divorce. It was all too much.
"The life stuff just had a gravitational pull," said the stay-at-home mom from Reno, Nev., who's in her mid-40s. "I just thought: I don't drink, I'm a good friend, a good mother, a good spouse — I should be a lot happier."
Godfrey's search for relief pointed her towards ketamine. Low, intravenous doses have been found to boost mood and curb suicidal thoughts, but the FDA has never approved ketamine as a treatment for depression. And the American Psychiatric Association (APA) warns patients about the potential for abuse and the lack of large, long-term studies of its effectiveness.
Even so, ketamine clinics like the one treating Godfrey have sprung up across the United States.
"The lack of information [on ketamine] is really quite dramatic when you look at the proliferation of use in certain communities," said former APA President Dr. Alan Schatzberg. He helped write an APA statement about ketamine urging caution.
A new, safer alternative?
Spravato, the drug approved Tuesday, is touted as a much safer cousin of ketamine.
Speaking this week with National Public Radio, Courtney Billington, president of Janssen Neuroscience, said that, unlike ketamine, "the amount of active ingredient that's in this product is at a very, very low dose."
In four studies that led to its approval, Spravato performed well against placebo, the FDA said, showing a "statistically significant effect compared to placebo on the severity of depression, and some effect was seen within two days." That's a much faster time to symptom relief than many antidepressants.
One longer-term trial suggests that Spravato's benefit lasts, the FDA said.
Side effects can occur, however.
"The most common side effects experienced by patients treated with Spravato in the clinical trials were dissociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk," the agency said.
Because of these potential effects, people with high blood pressure or certain vascular disorders should not take Spravato, and people should get a night of "restful sleep" before attempting to drive after taking the drug.
Also, "Spravato may cause fetal harm and women of reproductive potential should consider pregnancy planning and prevention; women should not breastfeed while being treated," the FDA said.
How do medicines like Spravato and ketamine help ease depression?
It's not clear, Schatzberg said. One common theory is that they affec the brain's response to the neurotransmitter glutamate. Neurotransmitters are chemicals that send signals from one part of the brain to another and from the brain to the body. Essentially, the thinking goes, these meds rewire the brain.
But Schatzberg, a professor of psychiatry and behavioral sciences at Stanford University, was part of a small study published online recently in The American Journal of Psychiatry. It suggested another explanation — that ketamine somehow activates opioid receptors in the brain.
That's potentially troubling, he said.
"We could be exposing people to untoward consequences from a drug that works through an opioid mechanism," he said. With an opioid addiction crisis in full swing across the United States, "we need to study [ketamine] more," he added.
For her part, Godfrey said ketamine has been nothing short of a miracle for her. Before that, she had tried a series of antidepressants before finding one that helped a bit, and everything from acupuncture to yoga and meditation. But her gloom and pain never seemed to go away.
"I did not think that anything with this much relief and promise would come along in my lifetime, let alone now," Godfrey said. "It's a game-changer."