In a National Institutes of Health trial, a drug is being studied as a fast-acting mood enhancer that restores pleasure-seeking behavior, independent of its other antidepressant effects. Approximately 40 minutes after receiving a ketamine infusion, treatment-resistant bipolar disorder patients experienced a reversal of a key symptom, which is a loss of interest in pleasurable activities. The effects of the ketamine infusion last for about 2 weeks and scans of the brain showed the agent’s action increased activity in areas in the front and deeply in the right hemisphere of the brain.

According to Carlos Zarate, M.D. of the NIH’s National Institute of Mental Health, “Our findings help to deconstruct what has traditionally been lumped together as depression. We break out a component that responds uniquely to a treatment that works through different brain systems than conventional antidepressants, and link that response to different circuitry than other depression symptoms.”

Does Ketamine Help in Treatment-Resistant Bipolar Disorder?

Though the loss of the ability to look forward to pleasurable activities is considered one of the two main symptoms of depression and bipolar disorder, effective treatments for this issue do not exist. Long used as an anesthetic and sometimes a club drug, ketamine has recently become the focus of a potential new class of rapid-acting antidepressants that can lift a person’s mood within hours instead of weeks.

Based on previous studies done by the NIMH, researchers believe ketamine’s therapeutic action against loss of interest in pleasurable activities would be traceable, to effects on a mid-brain area linked to reward-seeking and that it would follow a predictable time pattern and course.

Levels of anhedonia dropped within 40 minutes of a patient receiving an infusion of ketamine, compared with people who received a placebo in the study. Other symptoms of depression in the ketamine group improved within 2 hours.

Researchers then scanned a subset of ketamine-infused treatment patients, using PET scans, that showed which parts of the brain are activated by tracing the destinations of radioactively-tagged glucose, which is the brain’s fuel. The scan showed ketamine jump started activity not in the middle brain where researchers expected it, but instead deeply in the dorsal or upper anterior cingulate cortex, near the front middle the brain and putamen, located deep in the right hemisphere.

The level of boosted activity in these areas might reflect an increased motivation towards the ability to look forward to pleasurable activities, noted researchers. The findings of the study add evidence to support the antidepressant efficacy in targeting the neurochemical pathway.

Ongoing research is needed to discover more practical ways of delivering ketamine and related experimental antidepressants, such as a nasal mist.

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