Ketamine Infusions for Major Depression Disorder

Depressive Disorder, Major Clinical Trial

— Ketamie  

Official title:

Evaluation of Safety and Efficacy of Sub-anesthetic Ketamine Infusions as a Treatment for Patients Diagnosed With Resistant Major Depression

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02219867
• Other study ID #: Sheba- Ketamine
• Status: Not yet recruiting
• Phase: N/A
• First received: August 12, 2014
• Last updated: August 28, 2014
• Start date: August 2014
• Est. completion date: August 2017

Study information

• Verified date: August 2014
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Ketamine has been safely used for induction and maintenance of anesthesia for decades and more recently has been used for chronic pain. Ketamine is a noncompetitive, high-affinity antagonist of the N-methyl-D-aspartate type glutamate receptor, with additional effects on dopamine and μ-opioid receptors. During the last 9 years several uncontrolled reports have been published, showing a rapid and impressive effect of ketamine in TRD patients (Berman, Cappiello et al. 2000; Zarate, Singh et al. 2006; Mathew, Murrough et al. 2010; Aan Het Rot, Zarate et al. 2012; Mathew, Shah et al. 2012; Murrough, Iosifescu et al. 2013). Recently three placebo-controlled trials showed that a single dose of sub-anesthetic, (0.5 mg/kg) slow intravenous (IV) ketamine improves depressive symptoms dramatically. Across studies, a clinically significant antidepressant response was maintained for up to 72 hours in 12 of 25 patients. Nonetheless, all but two patients relapsed <2 weeks post-ketamine (Zarate, Singh et al. 2006; aan Het Rot, Zarate et al. 2012). Rot et al. showed that repeated IV ketamine infusions prolongs the duration of improvement.

The investigators believe that the data presented above allows us to provide ketamine treatment here in the Sheba Medical Center for TRD patients.

Description:

Major depressive disorder (MDD) is one of the leading causes of disability worldwide (Collins, Patel et al. 2011). A substantial proportion of patients do not achieve adequate remission despite multiple antidepressant trials and augmentation strategies (Rush, Trivedi et al. 2006; Weissman, Pilowsky et al. 2006). Treatment-resistant major depression (TRD) is defined as an insufficient response to at least two adequate antidepressant trials (Rush, Trivedi et al. 2006). Many of these patients are referred to previous somatic treatment e.g. electroconvulsive therapy (ECT), rapid Transcranial Magnetic Stimulation (rTMS) and Vagal Nerve Stimulation (VNS), all of which have serious disadvantages and/or limited efficacy.

Ketamine has been safely used for induction and maintenance of anesthesia for decades and more recently has been used for chronic pain. Ketamine is a noncompetitive, high-affinity antagonist of the N-methyl-D-aspartate type glutamate receptor, with additional effects on dopamine and μ-opioid receptors. During the last 9 years several uncontrolled reports have been published, showing a rapid and impressive effect of ketamine in TRD patients (Berman, Cappiello et al. 2000; Zarate, Singh et al. 2006; Mathew, Murrough et al. 2010; Aan Het Rot, Zarate et al. 2012; Mathew, Shah et al. 2012; Murrough, Iosifescu et al. 2013). Recently three placebo-controlled trials showed that a single dose of sub-anesthetic, (0.5 mg/kg) slow intravenous (IV) ketamine improves depressive symptoms dramatically. Across studies, a clinically significant antidepressant response was maintained for up to 72 hours in 12 of 25 patients. Nonetheless, all but two patients relapsed <2 weeks post-ketamine (Zarate, Singh et al. 2006; aan Het Rot, Zarate et al. 2012). Rot et al. showed that repeated IV ketamine infusions prolongs the duration of improvement.

The investigators believe that the data presented above allows us to provide ketamine treatment here in the Sheba Medical Center for TRD patients.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: August 2017
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Diagnosis of Major Depressive disorder, chronic and/or recurrent of at least at moderate severity, determined as reflected by baseline scores of =32 on the Inventory of Depressive Symptomatology -Clinician rated IDS-C30

• Patients with demonstrated insufficient response to =2 adequate antidepressant trials in the current episode

Exclusion Criteria:

• Current psychotic or dissociative symptoms

• Severe personality disorder with psychosis or dissociative symptoms

• Lifetime history of psychotic mania

• Substance use disorder

• Current suicidal ideation

• Uncontrolled elevated blood pressure, non-sinus rhythm, unstable ischemic heart disease, uncorrected hyper thyroidism, and for women, pregnancy or the initiation of or female hormonal treatment <3 months

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• Ketamine
Drug (including placebo)

Locations

Country	Name	City	State
Israel	Sheba MC	Ramat Gan

Sponsors (2)

Lead Sponsor	Collaborator
Sheba Medical Center	Tel Aviv University

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hamilston depression Rating Scale		Up to 30 days from last treatment	No
Primary	Montgomery Asberg Rating scale - MADRS		24 hours after treatment	No
Secondary	Side effects monitoring	Blood pressure monitoring Dissociative symptoms detection and description	Up to 4 hours after ketamine infustion	Yes