Ketamine Strengthens Antidepressant Case in 2017


The longtime anesthetic has shown strong, fast-acting efficacy in drug-resistant MDD patients.

MD Magazine

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An article titled, “The Dangers of Using the Club Drug Ketamine for Depression” ran online on Time in early March. Two months later, the site ran another article on the anesthetic drug, adversely titled, “New Hope for Depression.”

The synthesized drug, approved by the US Food and Drug Administration (FDA) in 1970 as an injection anesthetic treatment, is as known for its efficacious results as an investigative pain relief and antidepressant as it is for its recreational use. It has been trickling into clinical studies for the past few years.

In 2017, its clinical availability exploded, Steve Levine, MD, told MD Magazine. As a result, so did its popularity.

“It’s a paradigm shift from the past 50 years of what to expect in response and treatment time, so more people are on board,” Levine, founder of Actify Neurotherapies, said.

In 2 administered forms — an esketamine nasal spray developed by Johnson & Johnson (JNJ-54135419) and the hydrochloride injection from JHP Pharmaceuticals (Kelatar) — the NMDA receptor agonist has been given new consideration for market use this past year.

The esketamine nasal spray, after receiving Breakthrough Therapy designation from the FDA for major depressive disorder (MDD) patients with imminent risk of suicide in August 2016, underwent phase 3 trials in 2017. Based on clinical results, Johnson & Johnson will be seeking indications for treatment-resistant depression as well.

The benefit of the drug is in its fast-acting efficacy. In considering the importance of patient selection and safe administration for Kelatar, researchers from the Washington University School of Medicine’s Department of Psychiatry called the treatment a “rapid and robust” antidepressant.

"If clinical studies continue to support the antidepressant efficacy of ketamine, psychiatry could enter an era in which drug infusions and deliveries with more rapid responses become common,” researchers wrote.

By blocking the NMDA receptors for glutamate, its targeting differs from other common antidepressants, and causes a rapid onset reaction within hours of administration in off-label studies.

The only psychiatry therapy Levine could draw likeness to was electroconvulsive therapy (ECT). While the effects of ECT are not as adverse as depicted in media such as in the film “One Flew Over the Cuckoo’s Nest”, Levine said it’s the only comparator to ketamine’s treatment time and differentiation from standard care.

“This is pretty unique,” Levine said. “It’s pretty impressive we have something somebody can have as a procedural treatment, and feel better almost immediately. Everything else is just weeks or months.”

While nasal esketamine is notably closer to FDA consideration than the off-label intravenous therapy, Levine predicted patient acceptance to nasal administration will be more difficult, possibly due to its reputation as a recreational drug with strong effects.

As a result, injection therapies would be probably be administered in an acute-care setting, such as in emergency departments or hospitals, and serve as a bridge treatment to the nasally-administered form. Esketamine would then be administered by health care professionals.

“The advantage will really be in patient access to care,” Levine said. “If it’s FDA-approved, it’s likely to be covered by many health care companies. In IV (intravenous) Kelatar, it’s desirable to have the IV route. But with a much narrower mechanism than esketamine, it’s tough to see if will be as effective of a drug.”

There’s still consideration to be made to ketamine’s dosing regimens and adverse effects — researchers cited concern for its limited safety profile earlier this year — and patients must overcome its reputation as an abused recreational drug.

But after a half-century of lull in antidepressant development, Levine believes the field is at the cusp of new fast-acting therapies, biomarker research, and clinical developments that will guide future treatment. He said he’s rooting for ketamine approvals for the US market.

“It seems like we really in an interesting point in the history of psychiatric treatment and medication,” Levine said. “Things have been stagnant. I’m really excited for what’s coming down the pipe for 2018 and beyond.”

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