In a study from Inserm, CNRS, Sorbonne University, and elsewhere, scientists identified one of the mechanisms explaining the ketamine effect as an antidepressant.
Ketamine, usually used as an anesthetic, was administered to patients with severe resistant depression.
This treatment led patients to present an increased ability to overcome their negative beliefs about themselves and the world when researchers presented them with positive information.
These results open new therapeutic avenues for the management of antidepressant-resistant mood disorders.
About one-third of people with depression do not respond to the most prescribed antidepressants, leading to a diagnosis of treatment-resistant depression (TRD).
For these people, finding new and effective therapies is a priority.
Ketamine, a commonly used anesthetic, has been shown to influence resistant depression.
While conventional antidepressant treatments take time to be efficient (on average three weeks), ketamine has a rapid antidepressant effect, only a few hours after administration.
The mechanisms associated with this fast-acting antidepressant effect are still unknown.
In the study, the team coordinated a clinical study involving 26 antidepressant-resistant patients (TRD) and 30 healthy controls.
Patients and healthy subjects were first asked to estimate the probability of 40 “negative” events which could occur in their lives (e.g., have a car accident, get cancer, or lose their wallet).
After being informed of the actual occurrence risks in the general population, patients and healthy subjects were again asked to estimate the probability of these events occurring in their lives.
The research team showed that healthy people tended to update their initial beliefs more after receiving factual and positive information, which was not the case in the depressed patient population.
In the suite of the study, antidepressant-resistant patients received three administrations of ketamine at a subanesthetic dose (0.5 mg/kg over 40 minutes) in one week.
Only four hours after the first administration, patients’ ability to update their beliefs after receiving positive information was increased.
They became less sensitive to negative information and recovered an ability to update their knowledge comparable to that of the control group.
Moreover, improvement in depressive symptoms after ketamine treatment was associated with these changes in belief updating, suggesting a link between clinical improvement and changes in this cognitive mechanism.
The team suggests that patients with antidepressant-resistant depression showed a significant decrease in symptoms and became more receptive to “positive” experiences after one week of ketamine treatment.
This work highlights for the first time a cognitive mechanism potentially involved in the early effect of ketamine. It paves the way to new research on antidepressant therapies modulating the mechanisms of belief updating.
If you care about depression, please read studies about mindfulness therapy that could benefit people with depression, and this depression drug can improve cognitive function quickly.
For more information about mental health, please see recent studies that widely used depression drugs may lead to higher death risk, and results showing how your eating rhythms impact your mental health.
The study was conducted by Dr. Hugo Bottemanne et al and published in JAMA Psychiatry.
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