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Lally N, Nugent AC, Luckenbaugh DA, Ameli R, Roiser JP, Zarate CA. 
“Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression”. 
Transl Psychiatry. 2014;4:e469.
Anhedonia-which is defined as diminished pleasure from, or interest in, previously rewarding activities-is one of two cardinal symptoms of a major depressive episode. However, evidence suggests that standard treatments for depression do little to alleviate the symptoms of anhedonia and may cause reward blunting. Indeed, no therapeutics are currently approved for the treatment of anhedonia. Notably, over half of patients diagnosed with bipolar disorder experience significant levels of anhedonia during a depressive episode. Recent research into novel and rapid-acting therapeutics for depression, particularly the noncompetitive N-Methyl-D-aspartate receptor antagonist ketamine, has highlighted the role of the glutamatergic system in the treatment of depression; however, it is unknown whether ketamine specifically improves anhedonic symptoms. The present study used a randomized, placebo-controlled, double-blind crossover design to examine whether a single ketamine infusion could reduce anhedonia levels in 36 patients with treatment-resistant bipolar depression. The study also used positron emission tomography imaging in a subset of patients to explore the neurobiological mechanisms underpinning ketamine's anti-anhedonic effects. We found that ketamine rapidly reduced the levels of anhedonia. Furthermore, this reduction occurred independently from reductions in general depressive symptoms. Anti-anhedonic effects were specifically related to increased glucose metabolism in the dorsal anterior cingulate cortex and putamen. Our study emphasizes the importance of the glutamatergic system in treatment-refractory bipolar depression, particularly in the treatment of symptoms such as anhedonia.
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Oct 22, 2014 21:07
Increased Life Enjoyment for 14 Days after Ketamine #

Investigators gave depressed, "anhedonic" participants 0.5mg per kilogram of IV ketamine or placebo and then measured their mood and sense of life enjoyment. The researchers found that measures of anhedonia went down for two weeks after a single "sub-anaesthetic dose" of ketamine.

"All participants received one intravenous infusion of ketamine hydrochloride, administered at a subanesthetic dose of 0.5 mg kg−1, and one infusion of placebo (0.9 saline solution) in a randomized order over a 4-week study period, and with 2 weeks between each infusion."

Questions on the anhedonia measuring scale they used (SHAPS) include such questions as "I would enjoy being with family or close friends."; "I would be able to enjoy my favorite meal." ; and "I would get pleasure from helping others.".

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