Treatment Resistant Depression (Pilot)

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 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).

Conditions

• Depressive Disorder, Treatment-Resistant

Interventions

DRUG

Ketamine

Controlled IV ketamine infusion (0.00225mg/kg-min. \[18% (0.0125 mg/kg-min.).

DRUG

Clonidine

Participants will receive an approximately 5-day pretreatment of clonidine (max. dose 1mg/day divided doses) prior to and throughout the ketamine infusion.

DRUG

placebo

IV saline (i.e. placebo ketamine)

Sponsors & Collaborators

• Florida Atlantic University

  collaborator OTHER

• Washington University School of Medicine

  lead OTHER

Principal Investigators

• Eric Lenze, MD · Washington University School of Medicine

• John W Newcomer, MD · Washington University School of Medicine

• Nuri B Farber, MD · Washington University School of Medicine

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-04-30

Primary Completion

2014-06-06

Completion

2015-06-05

Countries

• United States

Study Locations