Cedars-Sinai Blog

An Expert's Take on the New Ketamine Depression Treatment

The first new drug approved in decades for one of the most common mental health problems is derived from ketamine.

More than 16 million people in the US have depression—and the existing treatments don't offer relief for many. Up to 25% of patients treated with medicines or therapy say they don't help.

"We need better treatments to help people with depression."

A nasal spray derived from ketamine—a widely used anesthetic and once-popular party drug—was recently approved by the Food and Drug Administration (FDA).

It's the first new drug approved in decades for one of the most common mental health problems.

"This is an important and exciting development," says Dr. Waguih William IsHak, a professor of psychiatry at Cedars-Sinai.

"We need better treatments to help people with depression."

In trials of the nasal spray, patients reported relief from their depression symptoms within hours or days of taking the medication—a big difference from the 2-3 weeks it typically takes for an antidepressant to kick in.

First new treatment in decades

The new drug is noteworthy because it's the first in decades that works differently from the antidepressants that are already widely available.

MAOIs, or monoamine oxidase inhibitors, were the first type of antidepressants developed. They were followed by SSRIs, or selective serotonin reuptake inhibitors, such as Prozac, Paxil, Zoloft, and Lexapro.

Both MAOIs and SSRIs work by targeting neurotransmitters in the brain.

"We had a long wave of drugs that were very similar," Dr. IsHak says.

No one is quite sure exactly how ketamine works in the brain, Dr. IsHak says, but it's believed that it works on a set of chemicals in the brain that regulate neurotransmitters, rather than working on the neurotransmitters themselves.

Treatment with strict safety guidelines

The idea of using ketamine for depression isn't new.

For more than a decade, doctors have studied using the medication in an IV form to treat depression. The results were dramatic, but patients would regularly relapse into depression within a couple of weeks.

Pill forms of the drug caused a high level of side effects.

So far, only the nasal spray has been approved by the FDA.

But the treatment comes with strict safety requirements: Patients must take it in a doctor's office, be monitored for at least 2 hours, enter their experience into a registry, and they can't drive on the day they take their dose.

The nasal spray is to be used twice a week for a month, followed by monthly doses as necessary for maintenance.

The monitoring is for good reason, says Dr. IsHak, who has studied the use of ketamine to address depression, especially in people who also suffer chronic pain. He was among the experts who presented information on ketamine to the FDA during the fact-finding stage of the approval process in late 2018.

The drug can have a host of side effects: dissociation (disconnection from your thoughts, feelings, and identity), hallucinations, blood pressure changes, irregular heartbeat—and it's potentially addictive.

Who should consider the new nasal spray?

People who have tried 2 or more antidepressants without results should consider the ketamine-derived spray, Dr. IsHak says.

Another group that might benefit is individuals who suffer from depression and chronic pain, which is known to improve with ketamine.

"This is an important group to address, especially given the opiate epidemic we are experiencing," Dr. IsHak says. "We need alternatives to opiates to help patients deal with pain."

Better help for people with depression

Dr. IsHak is hopeful that the new treatment will be successful for people with depression.

"I'm not very satisfied with the current treatment options we have for people with depression," he says.

He breaks down 3 reasons:

  • They're slow to work. People typically have to wait 2-3 weeks for any results, followed by time to adjust dosages or change medications.
  • They don't work well enough. Only about 30% of people see their depression go into remission after the first time they're treated. That increases to 60% with repeated attempts at treatment. "We're still very, very far from where we need to be," he says.
  • The side effects are hard on patients. One of the most common is sexual dysfunction. "It's underreported and under-discussed," he says. "That complicates relationships."