Ketamine Rapidly Restored Pleasure-Seeking in Bipolar Disorder

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Ketamine rapidly restored pleasure-seeking behavior ahead and independent of its other antidepressant effects in treatment-resistant depressed bipolar disorder patients, according to a report in Medical News Today.

Loss of interest in pleasurable activities, or anhedonia, is considered one of two key symptoms of both depression and bipolar disorder, but effective treatments for this symptom have been lacking.

Ketamine, which has been used as an anesthetic and sometimes a club drug, has lately been the focus of research on a potential new class of rapid-acting antidepressants that can improve symptoms within hours instead of weeks.

In a National Institute of Mental Health (NIMH) trial, researchers infused ketamine or a placebo into 36 patients in the depressive phase of bipolar disorder. They used rating scales for anhedonia and depression to detect any changes in mood. By separating anehodia items from other depression symptoms, researchers found that ketamine had a strong anti-anhedonia effect sooner than, and independent of, its other effects.

Levels of anhedonia dropped within 40 minutes of ketamine infusion, with results lasting up to 2 weeks in some patients. Other depressive symptoms improved within 2 hours.

Using PET scans on ketamine-infused patients, researchers found that the drug activated the dorsal anterior cingulated cortex rather than the expected middle brain area. Confirmation of these imaging findings depends on results of a similar NIMH ketamine trial in patients with unipolar major depression.

These findings add to other evidence supporting the antidepressant efficacy of targeting glutamate and dopamine. Currently, however, ketamine is not FDA-approved as a treatment for depression.

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Ketamine is being studied as a potential new class of rapid-acting antidepressants

A drug being studied as a fast-acting mood-lifter restored pleasure-seeking behavior independent of and ahead of its other antidepressant effects in a National Institutes of Health trial. Within 40 minutes after a single infusion of ketamine, treatment-resistant depressed bipolar disorder patients experienced a reversal of a key symptom — loss of interest in pleasurable activities — which lasted up to 14 days.

"Our findings help to deconstruct what has traditionally been lumped together as depression," explained Carlos Zarate, MD, of the NIH's National Institute of Mental Health. "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."
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