Handwriting Chemical formula of Ketamine with pen.

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PARIS, France — Most antidepressants take around three weeks to take effect, while studies consistently show ketamine works within hours. However, the mechanism which makes the drug work has remained unclear. Now, researchers from the Paris Brain Institute have discovered one answer that explains ketamine’s lightning-fast course of action.

Close to a third of depression patients don’t respond well to conventional therapies, with doctors classifying them as having treatment-resistant depression (TRD). Mental health issues can be aggressive, which makes finding effective treatments population absolutely imperative. To explore this, the researchers conducted their clinical study with 26 TRD patients and 30 healthy controls. Both patients and healthy participants had to estimate the probability of 40 “negative” events that could possibly occur in their lives, such as getting into a car accident, having a doctor diagnose them with cancer, or misplacing their wallet.

Study authors then revealed the risks associated with each event occurring relative to the general population to each participant. After, the team posed the same question to them in order to see how their thoughts changed when presented with the statistics. Their results show that after receiving information to help put things in perspective, the healthy participants changed their answers to reflect more realistic outcomes. Unfortunately, the answers from depressed patients didn’t show this trend.

The researchers then distributed ketamine to TRD patients and repeated this experiment. They received three doses of ketamine within one week, but it didn’t even take that long to notice a positive change. Just four hours after receiving the first dose, the patients were able to think much more optimistically. They were less sensitive to upsetting information and had a firmer grasp on receiving new facts in a similar way to the healthy controls.

Is belief the biggest key to treating depression?

These findings suggest that improvement in depressive symptoms among TRD patients after receiving ketamine indicates an association between greater clinical outcomes and the mechanistic changes that the brain undergoes.

“In other words, the more patients’ belief updating ability was increased, the greater the improvement in symptoms was,” explains Dr. Hugo Bottemanne and researchers say in a media release.

This research is the first of its kind to shine a light on the cognitive mechanism involved in the rapid effects of ketamine therapy. It helps neurologists and healthcare professionals have more confidence in alternative antidepressant therapies that may soon support a greater number of patients. The team also points out that more research is imperative, largely due to the many side-effects that ketamine can cause. Careful consideration and individualized dosing may help better study this drug and apply it in widespread clinical practice.

The findings are published in the journal People.

About Shyla Cadogan, RD

Shyla Cadogan is a DMV-Based acute care Registered Dietitian. She holds specialized interests in integrative nutrition and communicating nutrition concepts in a nuanced, approachable way.

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