This open-label study (n=97) investigated the effects of six intravenous ketamine infusions (35mg/70kg) on anhedonia (the inability to feel pleasure) in patients with major depressive disorder (MDD) (n=77) or bipolar depression (BD) (n=20). A significant reduction in the MADRS anhedonia subscale score was observed at 4hrs after the first infusion and was maintained with repeated infusions. Reductions were similar in both MDD and BD groups.

Abstract

“Objectives: Anhedonia is a common, persistent, and disabling phenomenon in patients with major depressive disorder (MDD) and bipolar depression (BD). This study was conducted to investigate the comparative effectiveness of repeated ketamine infusions in treating anhedonia in Chinese individuals suffering from MDD and BD.

Methods: Ninety-seven individuals suffering from MDD (n = 77) or BD (n = 20) were treated with six intravenous infusions of ketamine (0.5 mg/kg) administered over 40 min. Anhedonia was measured through the Montgomery–Åsberg Depression Rating Scale (MADRS). The antianhedonic response and remission were defined as ≥ 50% and ≥ 75% reduction in MADRS anhedonia subscale score one day after the sixth infusion, respectively.

Results: Anti-anhedonic response and remission rates after the sixth ketamine infusion were 48.5% (95% confidence interval = 38.3%–58.6%) and 30.9% (95% confidence interval = 21.6%–40.3%), respectively. When compared to baseline, a significant reduction in the MADRS anhedonia subscale score was observed at 4 h after the first infusion and was maintained with repeated infusions at any time point (all Ps < 0.05). The anti-anhedonic effect of ketamine did not differ between the MDD and BD groups.

Conclusion: This preliminary study found that repeated ketamine infusions appeared to be effective at rapidly ameliorating anhedonia, with similar efficacy in MDD and BD.”

Authors: Wei Zheng, Li-Mei Gu, Chen-Hui Sun, Yang-Ling Zhou, Cheng Yu-Weng, Xiao-Feng Lan, Bin Zhang & Yu Ping-Ning

Author Highlights

This is the first study to comparatively examine the antianhedonic effects of repeated ketamine infusions in Chinese patients with major depressive disorder (MDD) and bipolar depression (BD).

Repeated ketamine infusions were effective in rapidly decreasing anhedonia levels in Chinese patients with depression.

The antianhedonic effects of repeated ketamine infusions were similar in both MDD and BD.

Summary of Comparative effectiveness of repeated ketamine infusions in treating anhedonia in bipolar and unipolar depression

Introduction

Anhedonia is a core symptom of both major depressive disorder (MDD) and bipolar depression (BD), and is associated with a poorer treatment outcome than non-anhedonic counterparts. However, no drug specifically targeting anhedonia has been approved.

Ketamine, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, has been shown to reduce suicidal ideation and ameliorate depressive symptoms in patients suffering from MDD and BD. Additionally, the neuroprotective effect of ketamine was also demonstrated in MDD and treatment-refractory BD.

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