Nonresponse to Ketamine in Treatment-Resistant Bipolar Depression.

Abstract

<h4>Objectives</h4>Ketamine is a prototypical rapid-acting antidepressant for treatment-resistant bipolar depression (TRBD), yet many patients do not achieve a meaningful response. This study explored features of ketamine nonresponse in TRBD.<h4>Methods</h4>In a post hoc analysis of a naturalistic study, 35 TRBD patients received a four-week ketamine regimen (intravenous 0.5 mg/kg or oral 2.0/2.5 mg/kg). Response was measured using the Montgomery-Åsberg Depression Rating Scale, and baseline sociodemographic and clinical features were compared between responders and nonresponders.<h4>Results</h4>Fourteen patients (40%) were nonresponders. They had a higher median number of psychiatric comorbidities (2 vs. 1; p = 0.0366), were more likely to have any psychiatric comorbidity (78.6% vs. 33.3%; p = 0.0153), and had greater prior benzodiazepine use (64.3% vs. 23.8%; p = 0.0332). No significant links emerged between individual comorbidities or baseline suicidality and response.<h4>Conclusion</h4>Ketamine demonstrates a favorable safety and tolerability profile for short time use in TRBD regardless of isolated baseline characteristics, although a more severe comorbidity burden and benzodiazepine use appear to be associated with nonresponse.<h4>Trial registration</h4>NCT04226963 and NCT05565352.

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