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

Abstract

Background Antidepressant 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. Methods Subjects 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. Results Twelve 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. Limitations Post-hoc design, small sample size, diagnostic heterogeneity. Conclusions: Static (FHP) and dynamic (improved depressive symptoms) factors may be clinically useful in predicting whether a patient will have an extended response to ketamine.

Efficacy and Safety of a Rapid Intravenous Injection of Ketamine 0.5 mg/kg in Treatment-Resistant Major Depression

“…In a large study of potential demographic and clinical predictors of response to ketamine in patients with TRD, baseline depression severity did not correlate with HDRS decrease at days 1 and 7 40 . In a later report by the same group, early MADRS decrease at 230 min and one day post-infusion was identified as a significant predictor of response at 2 weeks 36 . In the present study, higher depression severity at baseline was significantly associated with larger improvement at 4 weeks post-injection.…”

“…In keeping with previous research in patients with TRD and no history of (changes in vigilance, alertness, and cognitive performance) and 'dread of ego dissolution' (negative experience of derealization, depersonalization, cognitive disturbance, and loss of thought and self-control). Several studies reported that the intensity of psychotomimetic or dissociative symptoms predicted a larger decrease of depression severity and sustained effects of ketamine 11,[35][36][37] . In the present study, there was a tendency for an association between a larger MADRS decrease on the day of ketamine injection and a higher peak of BPRS positive symptoms, but no association with 5D-ASC dimensions.…”

The antidepressant efficacy of subanesthetic-dose ketamine does not correlate with baseline subcortical volumes in a replication sample with major depressive disorder

“…Unlike monoaminergic antidepressants, which often require weeks to months to achieve maximal efficacy, a single subanesthetic dose of ketamine produces a rapid (within hours) and potent antidepressant response (Coyle and Laws, 2015; Kishimoto et al, 2016; Newport et al, 2015). Antidepressant response to a single ketamine infusion is typically transient (lasting several days to 1 week), though a small percentage of subjects may experience an extended antidepressant effect (Niciu et al, 2014b; Pennybaker et al, 2017). …”

Ketamine – a prototype of rapidly acting antidepressant drugs

“…Wśród potencjalnych czynników, które mogą wskazywać na wydłużone w czasie przeciwdepresyjne działanie ketaminy wymienia się chorobę alkoholową u członków rodziny pierwszego stopnia, brak prób samobójczych, zaburzenia o charakterze dysocjacyjnym (głównie depersonalizacja) w trakcie wlewu leku i zanikające w krótkim czasie po jego zakończeniu, poprawa takich objawów depresji jak smutek i trudności w koncentracji dzień po wlewie, wysoki indeks BMI, niskie podstawowe poziomy adiponektyny, wysokie podstawowe stężenia witaminy B 12 , mutacja Val66Met genu kodującego czynnik neurotroficzny pochodzenia mózgowego (BDNF, ang. brain-derived neurotrophic factor) [32][33][34][35][36]. Kwestią sporną pozostaje wpływ płci na działanie przeciwdepresyjne ketaminy.…”