Li et al

Li et al was a well-designed study using well-established paradigms. The authors investigate a potential solution to the delayed treatment response seen with SSRIs using glutamate N-methyl D-aspartate receptor. It is seen in the rat model that ketamine is effective in reversing the effects of behavioral, morphological and physiological effects of depression. While the chronic unpredictable stress paradigm and the behavioral tests used are well established, the authors concede that they did not use any brain imaging techniques to supplement their results.

            This study seeks to solve the problems that previous papers discussed in this class explored. For example, papers discussed in week 1, Santarelli et al and Bessa et al, examined the effects of SSRIs on hippocampal neurogenesis and neuronal remodeling respectively. They ask why there is a delayed response to treatment in the use of these drugs and propose that it is due to different neuronal models. This paper speaks to these models proposing that ketamine works to reduce atrophy and decreases in spine density while reversing behavioral effects such as anhedonia. Because results in treatment response can be seen quickly, ketamine amongst other gultamatergic NMDA receptor antagonist may be a potential candidate for treatment of depression. The authors did not focus on length of response or sustainability of response, which causes me to wonder how sustainable a treatment this would be for humans. The question remains whether using ketamine in humans could be sustained, and if it could, would it lead to abuse? Should ketamine be proposed only as a short-term solution to depression while introducing an SSRI? Because the effects of long-term ketamine use remains to be seen in an animal model, further research would be needed to demonstrate the sustainability of response, demonstrating no decline in efficacy and any possible interactions between ketamine and more traditional treatments of depression.