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Ketamine based drug should be available for treatment resistant depression, says FDA panel

BMJ 2019; 364 doi: https://doi.org/10.1136/bmj.l858 (Published 22 February 2019) Cite this as: BMJ 2019;364:l858
  1. Joanne Silberner
  1. The BMJ

An advisory committee to the US Food and Drug Administration (FDA) has strongly endorsed esketamine, a derivative of the anaesthetic drug ketamine, for treatment resistant depression. The recommendation makes it likely that the agency will approve the drug for marketing in the US.

Injectable and oral ketamine is used for pain relief and sedation, and can cause amnesia. It is also used to sedate horses, and has illicit popularity as a “club drug” to induce hallucinations and calmness, or in the words of the website Vice, “to get wobbly.”1

If approved by the FDA, esketamine would be the first new treatment for major depression in decades. Some clinics in the US already offer it off-label and patients have reported that it works within hours instead of the weeks that other antidepressants can take.

At the FDA hearing on 12 February, manufacturer Janssen presented five studies of a nasal spray formulation of esketamine used on patients who had failed to respond to oral antidepressants.2

In one of the studies, 53% of patients showed significant improvements after a month, compared with 39% in the placebo group. Results from the other trials were less clear.

Fourteen committee members agreed that the drug is effective, and that its benefits outweigh its risks. Two members disagreed.

Side effects were common and transient. In one study, 42% of the patients in the drug arm reported dizziness, compared with 10% in the placebo group. And 39% of those who received the drug reported dissociation, compared with 19% of the placebo group. Other less common side effects included hypertension, lethargy, and anxiety.

Because of the side effects, the committee strongly recommended that, if approved, the drug should be used under direct medical supervision. Dosage is likely to be twice a week for four weeks, then weekly or biweekly.

One patient who came to the committee meeting called the experience “unique but not unpleasant.” Representatives of other patient groups lauded it as a breakthrough. “This is real hope for people living with treatment resistant depression,” said Andrew Sperling, who directs advocacy efforts at the National Alliance on Mental Illness.

“The benefits clearly outweigh the risks,” said committee member Matthew Rudorfer, head of treatment programmes at the National Institute of Mental Health. But he added, “It is reasonable to think that esketamine is not going to be the answer for everybody, as no treatment for depression is.”

The National Institute for Health and Care Excellence estimates that 2.7 million people in the UK have treatment resistant depression, and some specialist centres in the UK are administering ketamine intravenously. Last December, James Stone of the Institute of Psychiatry, Psychology, and Neuroscience told a press briefing that his clinic was overrun with patients wanting treatment. He predicted that the drug could reach the European market in two or three years.3

A spokesman for manufacturer Janssen said that the company was working through the European Medicines Agency for approval, and in the case of a no deal Brexit would apply directly to the Medicines and Healthcare Products Regulatory Agency.

The FDA’s final decision will be made by 4 March. Janssen has not announced how much esketamine will cost in the US.

Footnotes

  • Correction: On 25 February 2019 we changed the wording in the title from “ketamine” to “ketamine based drug” as the article is about esketamine.

References

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