Yale University has found that a single dose of nasal spray ketamine (esketamine) reduces acute symptoms of depression (at 4 and 24 hours) and suicidal thoughts in patients with an imminent suicide risk.

The positives

These results are a step forward in providing acute treatments for severe and treatment-resistant depression.

The mainstay treatments for depression take four to six weeks to be fully effective, which is impractical for acute symptoms and contributes to poor rates of compliance.

The negatives

Trials are underway to study the long-term use of esketamine and establish the optimal dosing regimen in the wider population.

Following successful development and regulatory approval, esketamine is likely to be a second- or third-line therapy for the treatment of depression, below the standard of care and indicated initially only in the most severe cases.

These trials will benefit from consultations with the medical and regulatory community on how best to approach the regulation and prescription of a drug with a strong potential for recreational abuse.

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This cautious approach to development is reflective of the opioid crisis in the US.

The rapid increase in prescription and non-prescription opioids for the management of chronic pain in the 1990s has led to staggering financial costs ($1 trillion this century) and was related to 64,000 deaths from overdose in 2016 alone.

The future

Trials are underway to validate esketamine within a large representative treatment population.

Researchers and regulators will have to work closely with public health officials to ensure the risk of misuse is minimized.

Even if ketamine were to fail at this stage, its proven clinical value in treating depression is still a success story and will sure spur the development of other glutamatergic therapies for depression.

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