Sharon Osbourne says ketamine helped her depression. Is this the next big trend?

What happens when traditional antidepressants don't work? Many are turning to what psychiatrists call a "breakthrough" solution: ketamine. 

Since the 1970s, researchers have studied the hallucinogenic drug as a promising treatment for severe depression. Its safety and efficacy have been widely analyzed in numerous clinical trials, and the controversial practice has even earned praise from high-profile celebrities like Sharon Osbourne, who recently credited ketamine for coping with social media criticism following her much-discussed exit from "The Talk."

"I went through three months of therapy," Osbourne said in September. "I had ketamine treatment and I got it all out. All the tears and everything that I felt. All of that, it's gone."

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Ketamine is often stigmatized due to its bad reputation as the party drug "Special K" when abused. But in a controlled medical setting, psychiatrists say it presents a life-changing solution for those who haven’t responded to conventional medications. A hallmark study published in 2000 brought widespread attention to its antidepressant and anti-suicidal effects, and more recent studies have supported ketamine's high rate of success in treating persistent depression.

"There are lots of patients who are frightened of ketamine," says Dr. Amanda Itzkoff, a psychiatrist and CEO of Curated Mental Health, a psychiatry practice making psychedelic-assisted mental health services accessible. "They had potentially first heard about the drug as a drug of abuse so they're not sure if it can be given safely. But in a safe medical setting, it's an excellent drug."

How does ketamine work as an antidepressant?

Ketamine is an FDA-approved anesthetic, and over the past few decades, it's also been hailed for its fast-acting antidepressant effects.

In 2019, the FDA officially approved esketamine, or ketamine nasal spray, for depression – specifically major depressive disorder with suicidal ideation and treatment-resistant depression (meaning that at least two alternative antidepressant treatments failed).

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Dr. Nolan Williams, an assistant professor in Stanford University's Department of Psychiatry and Behavioral Sciences, says it's unclear exactly how ketamine affects mood, because "there are many mechanisms happening at once." But rather than affecting dopamine or serotonin, neuroscience studies show that ketamine instead targets a neurotransmitter called glutamate, which promotes the brain's ability to create lasting, new lifestyle patterns.

Some experts have also speculated that the dissociative experience of a ketamine "trip"  may be responsible for reducing depressive symptoms. Though there's no evidence that the trip directly affects mood, Dr. Alexander Papp, a board-certified psychiatrist and voluntary clinical professor at UC San Diego, says some of his patients have credited ketamine's psychedelic properties to their improved outlook on life.

"Some patients close their eyes and all they see is nothing, yet they still get the antidepressant effect," Papp says. "But also … people have said the trip helps them come to important understandings of themselves or relationships. So it's not an absolutely necessary component, but it can be a useful addition for the treatment."

More: How to know if ketamine is the right choice to treat your depression

What to expect in a ketamine treatment session

Itzkoff says each session varies by patient, but standard treatment occurs twice a week for four weeks; then, once a week for another four weeks. It can legally be administered orally or through an IV injection, but intranasal ketamine is the only FDA-approved method so far.

During the session, people often experience an altered, trancelike trip that lasts approximately one or two hours. They may also be guided with talk therapy, also known as ketamine-assisted therapy.

"When (patients) are in a very vulnerable state, we're often trying to help them access different types of feelings," Itzkoff says. "That is most easily done when you have a very controlled, very safe setting." In order to keep the patient comfortable, she adds that she will offer to "dim the lights, prepare music, or give them eye shades … because ketamine can cause patients to feel a bit dizzy."

However, Williams explains "the FDA-approved procedure for esketamine does not involve or require psychotherapy."

"We can't say for sure if it is helpful or not helpful," he says. "If you look more generally, psychotherapy tends to be helpful but saying that psychotherapy on its own is necessary or psychotherapy definitively combined with ketamine is necessary – it's not a known thing."

The unique benefits of ketamine

One of ketamine's greatest benefits is that it works almost immediately – critical for those at imminent risk of suicidal behavior.

"A relatively large percentage of people actually report their mood feels better within hours after taking the drug," says Dr. Gerard Sanacora, director of the Yale Depression Research Program and co-director of Yale New Haven Hospital Interventional Psychiatry Service. "And that's what we would consider a very good prognostic indicator, which is a fancy way of saying if you start to feel better within hours or within a day, that's a good sign you're going to continue to feel better."

So far, research shows it has a high rate of success; a meta-analysis study conducted by Sanacora and his team in 2017 found that a single dose rapidly reduced suicidal ideation within a day in over half of participants with treatment-resistant depression.

In addition, ketamine may function as a safe alternative for those who experience undesirable side effects from traditional SSRIs, like restlessness or reduced sexual desire.

"If you're taking antidepressants daily, the reason people have side effects is because that drug is in there," Itzkoff says. "They have a blood level of that drug every day and that's what's necessary for the drug to work. When patients receive ketamine, they don't maintain a level of the drug for very long."

Ketamine is not a panacea

Despite its promise, ketamine is not a miracle drug. Along with side effects including nausea and spikes in blood pressure, experts caution it can be life-threatening to those with cardiovascular issues. Some psychiatrists also worry about its high potential for misuse.

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Sanacora also warns not everyone will be equipped to handle the out-of-body experience accompanying a ketamine trip.

"Things may look different, sound different, feel different," he says. "You can feel like you're floating and it can be pretty frightening to some people if they're not prepared for that."

While much research has supported the treatment, less is known about its long-term efficacy for depression, which is why it's important to have more longitudinal studies about the permanence of its antidepressant effect.

"We only know as far as the studies go," Williams says.

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This article originally appeared on USA TODAY: Ketamine therapy for depression praised by celebs. Here's what to know