Interest-activity symptom severity predicts response to ketamine infusion in treatment-resistant depression

Interest and activity are part of the positive mood domain. Evidence suggests the symptom domain of interest-activity at baseline as a clinical predictor for treatment response to traditional antidepressants. However, whether this domain is related to the response to a single low-dose ketamine infusion remains unclear.

Seventy-one patients with treatment-resistant depression were randomized to 3 treatment groups: a single 0.5 or 0.2 mg/kg ketamine or normal saline placebo infusion. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale before infusions and at postinfusion period (at 40 min and up to 2 weeks). Low (mild) versus medium versus high (severe) interest-activity symptom domain groups were classified on the basis of the cutoff point of ± 0.4 standard deviation. The effect of baseline interest-activity symptoms on outcomes was tested using generalized estimating equation models.

The interest-activity symptom domain as a continuous variable (β = 8.413, p = .016) was related to the trajectory of depressive symptoms. Stratified by levels of the interest-activity symptom domain, in the low interest-activity, 0.2 mg/kg ketamine infusion (β = 0.013) demonstrated the greatest antidepressant effect (p < .01) compared with 0.5 mg/kg ketamine (β = 0.739) and placebo infusions; however, in the high interest-activity, 0.5 mg/kg ketamine infusion (β = 0.001) demonstrated the best antidepressant effect (p < .01) compared with 0.2 mg/kg ketamine (β = 1.372) and placebo infusions.

The symptom domain of interest-activity was an independent predictor for the treatment response to a single low-dose ketamine infusion.