Age affects temporal response, but not durability, to serial ketamine infusions for treatment refractory depression

Older age is associated with slower and less durable antidepressant responses to intravenous ketamine in veterans with treatment-refractory depression. The study found that age-related declines in neuroplasticity may attenuate ketamine's mechanism of action, which involves glutamatergic signaling and synaptogenesis. Older patients took longer to achieve a clinically meaningful reduction in depression symptoms and were more likely to relapse sooner after the infusion series ended. The findings suggest that age is a key patient characteristic influencing the speed and durability of ketamine's antidepressant effects.

Study at a glance

Abstract

Background Ketamine is a rapid-acting treatment for patients with treatment refractory depression (TRD), however treatment responses are often transient and ketamine’s antidepressant action lacks robust clinical durability. Little is known about which patient characteristics are associated with faster or more durable ketamine responses. Ketamine’s antidepressant mechanism is proposed to involve modulation of glutamatergic signaling leading to long term potentiation (LTP) and synaptogenesis, and these neuroplasticity pathways have been shown to be attenuated with older age. We therefore investigated the impact of patient age on the speed and durability of ketamine’s antidepressant effects in veterans receiving serial intravenous ketamine infusions for TRD.