FDA May Soon Approve Version of 'Special K' for Severe Depression

Larry Bryant Jr. has been managing depression for much of his life, but prefers not to take antidepressants due to side effect concerns. He's encouraged by the potential future approval of an FDA-approved variant of ketamine. (Photo
Larry Bryant Jr.

"Depression and anxiety have been with me long before HIV ever entered the picture," says Larry Bryant Jr., 52, who was diagnosed with HIV in 1986 and is a longtime HIV and social justice activist, currently a field organizer at the American Civil Liberties Union (ACLU) branch in Washington, D.C., his hometown. He attempted suicide once in high school and again in college, when he was hospitalized a few times.

"It was largely just emotional swings with some environmental influence," he recalls, "but then once I was diagnosed with HIV in college, it was hell. It felt like I was in a car going 115 miles an hour, but I wasn't driving."

Absolutely the best first-line treatment for depression is talk therapy and/or medications, according to David Guggenheim, Psy.D., chief mental health officer at New York City's LGBTQ-serving Callen-Lorde health center, which sees many HIV-positive patients. "Most of our patients come in and benefit from therapy and the meds, such as Lexapro [escitalopram oxalate] or Abilify [aripiprazole], we're able to prescribe," he says.

He adds that up to 60% of patients find relief solely through individual or group therapy, including cognitive behavioral and trauma-focused therapy.

"But," he adds, "we also have patients with treatment-resistant depression who can make us feel a little bit desperate, so we're always looking for new avenues of treatment."

That's why Guggenheim was among those in the mental health profession who were intrigued to hear that an expert panel in February recommended that the Food and Drug Administration (FDA) approve a nasal-spray version of ketamine, a longstanding medical anesthetic and popular club drug, sometimes called "Special K," that gives some people hallucinogenic effects. Research dating back more than a decade has found that it often provides dramatic, swift relief to people with major, even suicidal, depression that has been resistant to existing treatments.

The FDA may approve the drug, Johnson & Johnson's Esketamine, a slightly tweaked version of the generic drug ketamine, as soon as sometime this month. That means that most public and private insurers would cover a treatment that, up until now, has only been available to people with depression off-label, at prices as high as $3,000 a visit. The drug also has shown promise for the relief of severe chronic pain.

HIV and Depression

Bryant is not alone among Americans with depression, and he is certainly not alone among those with HIV who also battle the mental illness. While about 6.7% of U.S. adults have depression, about 20% to 40% of the roughly 1.1 million U.S. adults living with HIV have depression, according to a major, multisite study of people living with HIV and depression that came out last year.

The study also found that the amount of time people with HIV were depressed was directly related to how many doctor appointments they missed, how likely they were to be virally suppressed, and their risk of death from any cause.

The relationship between HIV and depression is complicated. People may have contracted HIV in the first place in part due to depression -- which can lead to risky behavior and poor judgment. But then, of course, HIV -- as well as other factors including economic insecurity, stress around being a minority (person of color, sexual minority, gender minority, etc.), and past trauma -- can feed depression due to the stigma, secrecy, and shame sometimes attached to it.

Over the years, says Bryant, his depression has subsided without the need for medication. "It's mild and manageable now," he says, but he admits that sometimes it keeps him in bed the whole weekend. "I can't move, I don't eat, and I don't want to be around people." He says that he's avoided meds because of a fear of side effects "and of the stigmatization that comes with living with a mental illness."

But this kind of treatment could be helpful for people like Bryant, who either can’t or won’t take antidepressants. If the drug is approved, users "would be snorting a kind of vapor solution [with another medication in pill form] in the doctor's office starting a few times a week, then spacing it out" based on its effect, says Elias Dakwar, M.D., associate professor of psychiatry at Columbia University, who has been studying ketamine's ability to help cocaine users disrupt their addictive thinking.

"I've found that with cocaine users who aren't seeking treatment, a ketamine infusion increases their motivation to stop and reduces their cravings," he says, plus cutting the likelihood of picking up cocaine again for at least 72 hours. In a study, he found that over about five weeks, about 50% of cocaine users receiving the ketamine treatment became cocaine abstinent versus about 10% in the study arm without the ketamine. Six months later, he said, the majority of those who'd been in the ketamine arm remained abstinent.

For Bryant and other people with depression, the dissociative (or feeling constantly spaced out) side effects often associated with most psychiatric meds drives them away from maintaining treatment. The research presented by Johnson & Johnson showed that about 11% of people taking Esketamine did have dissociative side effects, but other studies show those side effects seemed to subside within two hours of administering the drug -- and it won’t be taken every day.

Dakwar says that he thinks Esketamine for depression will come to market within the year and that it might even take the place of electroconvulsive therapy, also known as shock therapy, which has been long used for treatment-resistant depression but can also have side effects including memory loss. "It's quite robust and quick," he says of the drug's alleviation of depression.

Researchers do not know exactly how or why ketamine seems to alleviate depression. "It seems to involve the NMDA receptor," says Dakwar. That receptor plays a role in the brain's ability to change and adapt to new information.

At any rate, assuming that the FDA approves Esketamine, it could mean a new avenue of relief for people with depression, with or without HIV, for whom existing antidepressants haven't worked and who can't afford to pay for exorbitant ketamine treatments out of pocket.

And that's good news to Bryant, who may one day need treatment but who leans away from antidepressants. (We should note that health plans, or even providers, might make patients try older treatments first before covering or prescribing Esketamine.)

"I remember vividly what was going on in my brain when I felt that suicide was my only option," says Bryant. "Anything that could keep me from seeing that space again? Absolutely."