Ketamine pill offers hope, and risks, for treatment-resistant depression Premium

Extended-release ketamine tablets offer a convenient, effective, and potentially safer treatment option for depression, according to clinical trials.

A new tablet that slowly releases the drug ketamine can ease treatment-resistant depression, offering an alternative to cumbersome clinic-based treatments for people with the condition, researchers have found in a clinical trial.

Ketamine, sometimes called a “party drug”, blocks the receptor for an excitatory neurotransmitter — those that cause neurons fire and send messages — called glutamate. It was originally used as an anaesthetic but researchers found that it had rapid antidepressant effects, acting within hours.

As such, health workers routinely prescribe ketamine to people with treatment-resistant depression, where antidepressants don’t improve symptoms, and with suicidal ideation.

It is most commonly administered intravenously (i.e. by injecting into the blood), and can also be delivered via an intranasal spray. However, in these routes ketamine can have many side effects, including headache, nausea, and drowsiness and serious ones like increased blood pressure, loss of focus or dissociation from reality.

As a result, clinicians monitor patients who have been given ketamine for two hours while the side effects subside. This means an in-clinic treatment protocol that those suffering from depressive symptoms have said are inconvenient and render the drug more inaccessible.

Previous reports have suggested that tablets that release ketamine slowly can improve symptoms of depression with fewer side effects. Based on these reports, a team led by Paul Glue at the University of Otago, in New Zealand, proposed that patients could dose themselves safely at home using slow-release ketamine tablets.

“If ketamine is formulated as an extended-release tablet where it takes about 10 hours to release, most ketamine is broken down in the liver before it can get into the blood,” Dr. Glue told The Hindu in an email. Ketamine’s metabolites – the compounds formed when the liver breaks ketamine down – are the main drivers of its antidepressant effects, he explained. “However, the lower blood ketamine levels mean patients experience few or no side effects.”