Low-dose ketamine infusion for treating subjective cognitive, somatic, and affective depression symptoms of treatment-resistant depression

Backgrounds: Whether the antidepressant effects of low-dose ketamine infusion and the therapeutic impact of Val66Met brain-derived neurotrophic factor (BDNF) polymorphism vary across different depression symptom domains, namely affective, cognitive, and somatic, remains unclear. Methods: We-reanalyzed the data of Adjunctive Ketamine Study of Taiwanese Patients with Treatment-Resistant Depression (TRD). A total of 71 patients with TRD were randomized to three infusion groups: 0.5 and 0.2 mg/kg ketamine groups and the normal saline placebo group. The Beck Depression Inventory-II (BDI-II) was used to obtain self-reported scores prior to infusion and 240 min after infusion and sequentially on days 3, 7, and 14 after infusion. The three-factor model of cognitive, somatic, and affective depressive symptoms that is based on the BDI-II and proposed by Beck et al. was applied in the current study. The Val66Met BDNF polymorphism was genotyped. Results: Ketamine infusion exerted rapid and sustained antidepressant effects on the affective (p = 0.014) and cognitive (p = 0.005) depression symptom domains but not on the somatic (p = 0.085) depression symptom domain. Only patients with TRD harboring any Val allele at the BDNF rs6265 polymorphism were more likely to respond (p = 0.011) to low-dose ketamine infusion. Discussion: Additional studies should elucidate different mechanisms underlying the effects of ketamine infusion on cognitive, affective, and somatic depression symptom domains in patients with TRD.

Automated summary

In patients with treatment-resistant depression, low-dose ketamine infusion has rapid and sustained antidepressant effects on affective and cognitive depression symptom domains, but not on the somatic domain. Moreover, TRD patients carrying any Val allele at the BDNF rs6265 polymorphism are more likely to respond to low-dose ketamine infusion. Further studies are needed to understand the different mechanisms underlying the effects of ketamine infusion on cognitive, affective, and somatic depression symptom domains in TRD patients.