Nasal Spray Is A New Antidepressant Option For People At High Risk of Suicide

The Food and Drug Administration has approved a variant of the anesthetic and party drug ketamine for suicidal patients with major depression.

The drug is a nasal spray called Spravato and it contains esketamine, a chemical cousin of ketamine.

In 2019, the FDA approved Spravato for patients with major depressive disorder who hadn't responded to other treatments. Now, the agency is adding patients who are having suicidal thoughts or have recently attempted to harm themselves or take their own lives.

"Spravato is the first approved antidepressant medication that's been able to demonstrate a reduction in symptoms of major depressive disorder within 24 hours after the first dose," says Dr. Michelle Kramer, a psychiatrist and vice president of U.S. neuroscience, medical affairs at Janssen Pharmaceuticals, which makes the drug. Janssen is part of Johnson & Johnson.

The drug's quick action is potentially important for suicidal patients because "existing drugs typically can take weeks or longer before you really get noticeable clinical benefit," says Dr. Gerard Sanacora, a professor of psychiatry at Yale University and director of Yale's depression research program. He was involved in the studies leading to the FDA approval and has consulted for Janssen.

So a dose of esketamine "could potentially get a person out of a difficult, horrible situation when they're feeling so overwhelmed," says Dr. Charles Conway, a professor of psychiatry at Washington University School of Medicine in St. Louis who wasn't involved in the study. "This could be a significant improvement in how we can help people who have intense suicidal thinking."

Studies have found that more than 40% of suicidal patients who got the drug still had greatly reduced symptoms of depression a month later.

But esketamine was only partly responsible for that result. Patients in the studies were hospitalized for at least several days, received other antidepressants, and attended twice-weekly therapy sessions for four weeks, Kramer says.

"What we have to be careful of is not to interpret that this is a medication you give once or twice and the person's fine," Sanacora says. "Part of the reason that these studies showed such a big effect is that there was a very comprehensive follow-up plan built into this."

Although the drug comes in the form of a nasal spray, it is meant to be given in a hospital or clinic setting, not at home. Esketamine, like ketamine, can cause changes in blood pressure and heart rate, as well as out-of-body experiences for an hour or so after it is administered.

"Most patients describe it as feeling weird," Sanacora says, "similar to what you would get either waking up or going under anesthesia."

The patients who are candidates for esketamine will probably have been brought to an emergency room or psychiatric facility because of suicidal thoughts or behavior, Conway says. And those who get the drug will also most likely be admitted to a psychiatric unit.

Even though esketamine is not intended to prevent hospital stays, it might be able to shorten them, Sanacora says. "It is a real possibility if people are starting to feel better quickly," he says.

The studies that led to Spravato's approval were highly unusual because they included people at high risk of suicide.

"It really is the first large scale clinical trial like this to be done in a population of patients that not only have severe depression, but are also expressing acute suicidal ideation," Sanacora says. Until now, he says, antidepressant studies have usually "excluded this patient population."

Spravato's approval comes as many people are experiencing stress and anxiety related to the COVID-19 pandemic.

"The COVID environment is sort of the perfect cauldron of stress," Conway says, because it is leaving many people isolated, without jobs, and uncertain about the future. And those are factors that can contribute to depression and suicidal thoughts, he says.

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