Ketamine molecule:

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Ketamine Clinical Trials

A Safe Ketamine-Based Therapy for Treatment Resistant Depression

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Id: NCT01179009

Organisation Name: Washington University School of Medicine

Overal Status: Completed

Start Date: April 2012

Last Update: November 25, 2022

Lead Sponsor: Washington University School of Medicine

Brief Summary: Treatment resistant depression (TRD) is a major public health problem. Current therapeutic options for this patient population remain limited. With all available treatments, only a sub-set of those patients who achieve an antidepressant response are likely to achieve treatment-induced remission. The need for antidepressant medication that can provide both rapid and long lasting relief of TRD symptoms is widely recognized. There is new evidence that drugs that block NMDA glutamate receptors (NMDA antagonists) are promising candidates for meeting this need. Existing studies in TRD have used only a low-dose, brief infusion of ketamine that would not be expected to re-sensitize the NMDA receptor; in agreement with this theory, these prior studies have found only temporary improvements of depression. Our key hypothesis is that a higher-dose, longer-term ketamine infusion, such as that used in chronic pain studies, would provide a more robust and lasting improvement from depression.

Accordingly, we will be test whether a 100-hour ketamine infusion would be more effective than the standard 40-minute ketamine infusion currently used in other TRD studies. We will randomize subjects to one of 2 arms: (1) 100-hour (+/- 4 hours) ketamine infusion plus clonidine for the entire infusion (2) 40-minute ketamine infusion (plus clonidine) following a 100+/- hour saline infusion. All subjects will receive clonidine, an alpha-2 agonist, to minimize side effects of ketamine (namely, brief/mild psychotic and cognitive symptoms).

A subset of patients with TRD will also receive a 100-hour (+/- 4-hours) ketamine infusion with two head MRIs pre-infusion and one head MRI post-infusion and/or weekly maintenance IM injections of either ketamine or active CNS placebo, lorazepam for up to 16 weeks. Little research has been done on the mechanism of ketamine's putative antidepressant action. There is now a consensus that, in the early stages of the novel treatment development for depression, clinical studies should be paired with mechanistic studies (neuroimaging) to understand the underlying mechanism and validate this as a treatment target. Ketamine is thought to have an antidepressant effect by increasing synaptic connections and therefore increasing connectivity in critical cognitive/emotional circuits.

  • Depressive Disorder, Treatment-Resistant

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