Ketamine and Scopolamine Infusions for Treatment-resistant Major Depressive Disorder

Combination of Anticholinergic and Glutamatergic Effects in Treatment-resistant Major Depressive Disorder. A Pilot Study

Ketamine infusions resulted in an acute reduction in global depression scores and in severity of suicidal ideation. Scopolamine infusions produced also a significant improvement in depression that was sustained over time.

We therefore plan to investigate the feasibility and efficacy of open-label repeated intravenous administration of ketamine and scopolamine combined in this population of severely depressed, treatment-resistant patients. The results from this study could lead to the development of new strategies for the treatment of patients with TRD.

Study Overview

• Status: Withdrawn
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Ketamine; Drug: Scopolamine

Detailed Description

Patients will undergo two weeks of prospective observation, they will then receive IV infusions of ketamine, scopolamine or both per randomization as augmentation of their ongoing antidepressant regime. The schedule of administration will be twice a week of three weeks. After this phase the subject will be followed with assessments every two weeks for three months.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Depression Clinical and Reseach Program - MGH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Outpatients with sever treatment-resistant depression
• Currently depressed
• Currently under regular psychiatric care
• On an aggressive antidepressant regimen, stable for 4 weeks

Exclusion Criteria:

• No history of other major psychiatric illnesses, including bipolar disorder
• No history of psychosis
• No history of drug abuse
• No major medical illness or unstable medical condition.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine plus placebo; Subjects assigned to this paradigm will receive a 15 minute infusion of normal saline (placebo) followed by IV ketamine at 0.25mg/kg over 45 minutes twice a week for 3 weeks.	Drug: Ketamine; ketamine IV 0.25mg/kg infusions twice a week for 3 weeks as augmentation of ongoing antidepressant regimen.
Experimental: Scopolamine plus placebo; Subjects will receive a 15 minute infusion of IV scopolamine 2ug/kg followed by a 45 minute infusion of normal saline (placebo).	Drug: Scopolamine; Scopolamine 2ug/kg over 15 minutes twice a week for 3 weeks as augmentation of ongoing antidepressant regimen
Experimental: Ketamine plus scopolamine; Subject will receive an IV scopolamine infusion at a dose of 2ug/kg over 15 minutes, followed by an IV infusion of ketamine at a dose of 0.25mg/kg over 45 minutes.	Drug: Ketamine; ketamine IV 0.25mg/kg infusions twice a week for 3 weeks as augmentation of ongoing antidepressant regimen.; Drug: Scopolamine; Scopolamine 2ug/kg over 15 minutes twice a week for 3 weeks as augmentation of ongoing antidepressant regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Rating Scale - 28 items	Subjects will be assessed with HAMD-28	up to 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systematic Assessment for Treatment Emergent Events (SAFTEE)	Subjects will be monitored for emergence of side effects weekly for the first 8 weeks, then every two weeks for 8 weeks.	up to 4 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Cristina Cusin, M.D., MGH Department of Psychiatry

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: May 31, 2012
• First Submitted That Met QC Criteria: June 5, 2012
• First Posted (Estimate): June 7, 2012

Study Record Updates

• Last Update Posted (Actual): February 19, 2018
• Last Update Submitted That Met QC Criteria: February 15, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antiemetics; Gastrointestinal Agents; Adjuvants, Anesthesia; Mydriatics; Ketamine; Scopolamine; Butylscopolammonium Bromide
• Other Study ID Numbers: 2012-P-000624