Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression
Níall Lally, Allison C. Nugent, David A. Luckenbaugh, Rezvan Ameli, Jonathan P. Roiser, Carlos A. Zarate
Translational Psychiatry October 14, 2014 DOI: 10.1038/tp.2014.105 via OpenAlex
Summary
A single infusion of ketamine rapidly reduced anhedonia in 36 patients with treatment-resistant bipolar depression, and this effect occurred independently from reductions in general depressive symptoms. The anti-anhedonic effects were specifically related to increased glucose metabolism in the dorsal anterior cingulate cortex and putamen, highlighting the role of the glutamatergic system in treating such symptoms.
Study at a glance
| Characteristics | Randomized, placebo-controlled, double-blind crossover design Peer reviewed |
|---|---|
| Sample size | 36 |
| Population | Patients with treatment-resistant bipolar depression |
| Intervention | Ketamine infusion |
| Dose | single ketamine infusion |
| Topics | Depression Ketamine |
| Keywords | Bipolar disorder Depression economics Schizophrenia object-oriented programming Psychology |
| Citations | 269 |
| Key finding | Ketamine rapidly reduced anhedonia levels in patients with treatment-resistant bipolar depression, independently from reductions in general depressive symptoms. |
Abstract
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.