Therapeutic and Safety Outcomes of Intravenous Ketamine for Treatment-refractory Depression in a Veteran Population: A Case Series

ABSTRACT Introduction Major depressive disorder is a serious, recurrent, and disabling psychiatric illness. Despite many proven treatments with multiple medications or therapies, approximately 30% of patients fail to achieve remission and are considered to have treatment-refractory depression (TRD). Recently, there has been a growing interest in the use of intravenous (IV) ketamine for the treatment of TRD. There is limited yet increasing evidence to support the use of ketamine, a glutamate receptor antagonist, in the management of depression; however, the lack of data regarding the safety and tolerability of therapy has limited its clinical use. By analyzing a cohort of veterans with TRD and comorbid psychiatric conditions treated with IV ketamine infusions for a 24-month study period, we aim to provide critical information about ketamine’s clinical effectiveness and safety. Materials and Methods Based on a retrospective chart review, we identified eight veterans with TRD receiving treatment with repeated-dose IV ketamine from 2018 to 2020. The magnitude of clinical response was based on the Beck Depression Inventory self-report scale and the Patient Health Questionnaire-9, both measured at the initial patient consultation and before the beginning of each ketamine infusion treatment. Safety analysis included changes to pre- and post-ketamine infusion on vital signs, effects on alertness and sedation, and potential psychosis-like effects. For all outcomes, we estimated a linear mixed-effects model that allowed heterogeneous residual variances for each veteran. The effect of continuous predictor variables was estimated using restricted cubic splines with knot points specified at the 5th, 35th, 65th, and 95th percentiles. All the analyses were conducted using SAS v.9.4, with P