Therapeutic medications for the treatment of depression have serious limitations, particularly delayed onset and low rates of efficacy. However, the discovery that a single subanesthetic dose of ketamine, a glutamate NMDA receptor channel blocker, can produce a rapid (within hours) antidepressant response that is sustained (about 1 week), even in patients considered treatment-resistant, has...
Electroconvulsive therapy (ECT) employs the elective induction of generalizes seizures as a potent treatment for severe psychiatric illness. As such, ECT provides an opportunity to rigorously study the recovery of consciousness, reconstitution of cognition, and electroencephalographic (EEG) activity following seizures. Fifteen patients with major depressive disorder refractory to pharmacologic...
OBJECTIVES: Extant evidence indicates that ketamine exerts rapid antidepressant effects in treatment-resistant depressive (TRD) symptoms as a part of major depressive disorder (MDD) and bipolar disorder (BD). The identification of depressed sub-populations that are more likely to benefit from ketamine treatment remains a priority. In keeping with this view, the present narrative review aims to...
OBJECTIVE: The authors compared the efficacy of standard-of-care treatment plus intranasal esketamine or placebo for rapid reduction of symptoms of major depression, including suicidality, among individuals at imminent suicide risk. METHOD: In a double-blind, multicenter, proof-of-concept study, 68 participants were randomly assigned to receive esketamine (84 mg) or placebo twice weekly for 4...
BACKGROUND: The glutamatergic modulator ketamine has rapid antidepressant effects in individuals with major depressive disorder and bipolar depression. Thus, modulating glutamatergic transmission may be critical to effectively treating depression, though the mechanisms by which this occurs are not fully understood. METHODS: This double-blind, crossover, placebo-controlled study analyzed data...
Background Ketamine induces rapid and robust antidepressant effects, and many patients also describe dissociation, which is associated with antidepressant response. This follow-up study investigated whether antidepressant efficacy is uniquely related to dissociative symptom clusters. Methods Treatment-resistant patients with major depressive disorder (MDD) or bipolar disorder (BD) (n=126) drawn...
Current first-line antidepressants can take weeks or months to decrease depressive symptoms. Low dose ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, shows potential for a more rapid antidepressant effect, with efficacy also evident in previously treatment-resistant populations. However, a greater understanding of the physiological mechanisms underlying such effects is required....
Abstract Background Recognizing the importance not only of the clinician’s opinion but also of the patient’s experience and perspective, Sequenced Treatment Alternatives to Relieve Depression (STAR*D) utilized both clinician-reported and patient-reported outcomes in a large-scale multi-step study on antidepressant effectiveness in real-world settings. Both approaches indicate that <17% of Major...
PsychopharmacologyFebruary 1, 2018John Hartberg, Simone Garrett-Walcott, Angelo De Gioannis66 citations
Depressive episodes are the leading cause of mental health-related hospital admissions in Australia, and 44% of those admitted have a previous history of hospitalisations for depression (Admitted patient mental health-related care: (Australian Institute of Health and Welfare Aust Hospital Stat 2011-12, 2013). Despite numerous available antidepressant treatments, many patients do not respond to...
Rationale: The mechanisms responsible for the unique antidepressant properties of ketamine have only been partly resolved. Recent preclinical reports implicate the neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] in the antidepressant-like response of ketamine, and modulation of 5-HT1B receptors has been hypothesized to attain an important role. Objectives: To evaluate the role of...