Journal Article

Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression

Lin, Wei-Chen, Hong, Chen-Jee, Li, Cheng-Ta, Su, Tung-Ping, Chen, Mu-Hong, Bai, Ya-Mei, Tu, Pei-Chi, Krystal, John H, Cheng, Chih-Ming, Gueorguieva, Ralitza

2017

Overview

The antidepressant effects of ketamine are thought to depend on brain-derived neurotrophic factor (BDNF) genotype and dose. The purpose of this study was to characterize the dose-related antidepressant effects of ketamine in patients with treatment-resistant depression drawn from a Chinese population predominately possessing lower activity BDNF genotypes (Val/Met, Met/Met). We conducted a double-blind, randomized, parallel-group, placebo-controlled trial of a single ketamine infusion (saline, 0.2 mg/kg, 0.5 mg/kg). Patients (N=71; BDNF genotype: Val/Val (N=12, 17%), Val/Met (N=40, 56.3%), and Met/Met (N=19, 26.8%)) received mood ratings before infusion, after infusion, and for the subsequent 14 days. Plasma ketamine levels and BDNF genotypes were assessed. This study found a significant dose-related ketamine effect on scores on the Hamilton Depression Rating Scale (HAMD). The responder analysis (>50% reduction from baseline HAMD on at least 2 days between days 2 and 5) also revealed a significant dose-related effect (saline: 12.5%, 0.2 mg/kg: 39.1%; 0.5 mg/kg: 45.8%). This is the first report to our knowledge to demonstrate the dose-related efficacy of R/S-ketamine for treatment-resistant depression and the first to characterize ketamine effects in a genotyped Chinese population in which most (83%) patients possessed at least one copy of the lower functioning Met allele of the BDNF gene.

• Publisher: Nature Publishing Group
• Subject: Adult / Antidepressants / Antidepressive Agents - administration & dosage / Antidepressive Agents - blood / Asian Continental Ancestry Group - genetics / Blood Pressure - drug effects / Brain-derived neurotrophic factor / Brain-Derived Neurotrophic Factor - genetics / Depressive Disorder, Major - blood / Depressive Disorder, Major - drug therapy / Depressive Disorder, Major - genetics / Depressive Disorder, Treatment-Resistant - blood / Depressive Disorder, Treatment-Resistant - drug therapy / Depressive Disorder, Treatment-Resistant - genetics / Dose-Response Relationship, Drug / Double-Blind Method / Female / Genotypes / Heart Rate - drug effects / Humans / Ketamine / Ketamine - administration & dosage / Ketamine - analogs & derivatives / Ketamine - blood / Male / Mental depression / Middle Aged / Mood / Original / Patients / Polymorphism, Genetic / Psychiatric Status Rating Scales / Taiwan / Treatment Outcome / Treatment resistance