Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects

Abstract

Ketamine’s mechanism of action was assessed using gamma power from magnetoencephalography (MEG) as a proxy measure for homeostatic balance in 35 unmedicated subjects with major depressive disorder (MDD) and 25 healthy controls enrolled in a double-blind, placebo-controlled, randomized cross-over trial of 0.5 mg/kg ketamine. MDD subjects showed significant improvements in depressive symptoms, and healthy control subjects exhibited modest but significant increases in depressive symptoms for up to one day after ketamine administration. Both groups showed increased resting gamma power following ketamine. In MDD subjects, gamma power was not associated with the magnitude of the antidepressant effect. However, baseline gamma power was found to moderate the relationship between post-ketamine gamma power and antidepressant response; specifically, higher post-ketamine gamma power was associated with better response in MDD subjects with lower baseline gamma, with an inverted relationship in MDD subjects with higher baseline gamma. This relationship was observed in multiple regions involved in networks hypothesized to be involved in the pathophysiology of MDD. This finding suggests biological subtypes based on the direction of homeostatic dysregulation and has important implications for inferring ketamine’s mechanism of action from studies of healthy controls alone.

Plasma metabolomic profiling of a ketamine and placebo crossover trial of major depressive disorder and healthy control subjects

“…The subject population in this study included 29 MDD subjects who met DSM-IV TR criteria and 25 healthy controls, with an age range 18–65 (Nugent et al 2018). There were no significant differences in demographic characteristics between healthy controls and patients with MDD.…”

“…Individuals with a DSM-IV diagnosis of drug or alcohol dependence or abuse within the past 3 months, serious, unstable illness, or uncorrected hypo- or hyperthyroidism were excluded. Additional study details have been previously published (Nugent et al 2018). …”

Characterizing the course of suicidal ideation response to ketamine

“…Data from five independent studies of ketamine in treatment-resistant major depressive disorder (MDD) and bipolar I or II depression without psychotic features were combined; details regarding the patient population have been published previously (Diazgranados et al, 2010b; Ibrahim et al, 2012; Nugent et al, 2018; Zarate et al, 2012; Zarate et al, 2006). A total of 128 patients (ages 19 to 66 (M = 43.83, SD = 12.12); 58 males and 70 females; see Table 1) were admitted for study to the Mood and Anxiety Disorders research unit at the National Institutes of Health (NIH), Bethesda, MD, USA.…”

“…A total of 128 patients (ages 19 to 66 (M = 43.83, SD = 12.12); 58 males and 70 females; see Table 1) were admitted for study to the Mood and Anxiety Disorders research unit at the National Institutes of Health (NIH), Bethesda, MD, USA. Participants were screened and deemed eligible for further evaluation upon meeting research criteria, which included meeting criteria for a major depressive episode of at least moderate severity (≥ 18 on the Hamilton Depression Rating Scale (HAM-D) (Zarate et al, 2006) or ≥ 20 (Diazgranados et al, 2010b; Nugent et al, 2018; Zarate et al, 2012) on the Montgomery-Asberg Depression Rating Scale (MADRS). Once at the NIH, patient diagnosis was established using the Structured Clinical Interview for Axis I Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) (First et al, 2002) and corroborated by a team of clinicians using all available information.…”

Short but Continuous Natural Pain during Meditation Sittings for Depression Treatment: A Case Report

“…Similarly, conventional antidepressants and psilocybin might function through monoamine related pain pathways (25)(26)(27). However, shifting maladaptative states of the body make it an elusive goal to achieve remission, which could be supported by research findings such as distinct changes in depressive symptoms upon ketamine administration between depressed and healthy subjects (28).…”