The jury remains out on ketamine-based antidepressants. They work… for *some* people.

Science News covers the ups and downs of Spravato, a ketamine-related antidepressant nasal spray that works for some folks, sometimes:

Many existing antidepressants target serotonin, a chemical messenger in the brain involved in mood. Scientists think ketamine and its relatives affect a different chemical messenger, glutamate, sometimes within hours.

For all the fanfare over Spravato’s approval, ketamine’s power to quickly turn around severe depression in some people has been known for years. Freestanding clinics, as well as academic medical centers, offer intravenous infusions of ketamine to people with severe depression. For some patients, the treatment has been life-changing. Yet others don’t respond. “It’s not for everybody,” says Cristina Cusin, a psychiatrist who codirects the ketamine clinic at Massachusetts General Hospital in Boston.

Spravato received fast-track approval from the FDA based on what some critics call weaker-than-usual evidence: In two of three monthlong trials, Spravato didn’t outperform a placebo, for instance. Janssen Pharmaceuticals, the drug’s maker, is still tallying data and trying to determine which patients might be helped most by the drug.

Twenty-four hours after beginning treatment, the people taking Spravato scored on average almost four points lower on a 60-point depression scale than people who had received a placebo — a small but consistent difference. Yet, suicidal behavior did not differ between people who took Spravato and those who took the placebo; both groups improved.

Spravato comes with a long list of side effects: sleepiness, dizziness, anxiety and feelings of disconnection, vomiting, increased blood pressure and bladder problems. And like ketamine, Spravato can be abused. For these reasons, the FDA requires that the drug be taken only in a certified health clinic, so the patient can be monitored for several hours after using it.

As of mid-October, more than 2,000 clinical sites had been certified to dispense Spravato, according to Janssen.