Symptomatology and predictors of antidepressant efficacy in extended responders to a single ketamine infusion

•Some subjects display antidepressant response to ketamine two weeks post-infusion.•Two-week post-infusion data from multiple ketamine trials (MDD & BD) were combined.•Smoking history & family history of alcohol use were linked to response at two weeks.•Less sadness, anhedonia & trouble concentrating at day 1 predicted greater response.•Sleep quality was not significantly improved in responders at two weeks.

BackgroundAntidepressant response to a single subanesthetic dose infusion of the glutamatergic modulator ketamine is transient in most depressed patients; however, a minority continue to experience an extended response. This study examined depressive symptoms and potential clinical predictors of extended response to ketamine in subjects with mood disorders.MethodsSubjects were diagnosed with either major depressive disorder (MDD) or bipolar depression. All subjects were treatment-resistant and experiencing a major depressive episode of at least moderate severity. MDD subjects were unmedicated and those with bipolar depression were receiving therapeutic-dose lithium or valproate. All subjects received a single 0.5 mg/kg ketamine infusion. Data were collected pre-infusion (baseline) and at days one, 14, and 28 post-infusion.ResultsTwelve of 93 (12.9%) participants continued to meet response criteria (50% reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score) at two weeks. All depressive symptoms assessed by the MADRS were improved at two weeks in ketamine responders except for sleep duration/depth. A positive family history of alcohol use disorder in a first-degree relative (FHP) and greater dissociation during the infusion were associated with better antidepressant response at two weeks. Improved measures of apparent sadness, reported sadness, inability to feel, and difficulty concentrating at day 1 correlated most strongly with antidepressant effects at two weeks.LimitationsPost-hoc design, small sample size, diagnostic heterogeneity.ConclusionsStatic (FHP) and dynamic (improved depressive symptoms) factors may be clinically useful in predicting whether a patient will have an extended response to ketamine.