Ketamine and Scopolamine Infusions for Treatment-resistant Major Depressive Disorder

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Ketamine
* Drug: Scopolamine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine plus placebo<br>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<br>* ketamine IV 0.25mg/kg infusions twice a week for 3 weeks as augmentation of ongoing antidepressant regimen.<br>|
| Experimental: Scopolamine plus placebo<br>Subjects will receive a 15 minute infusion of IV scopolamine 2ug/kg followed by a 45 minute infusion of normal saline (placebo). | Drug: Scopolamine<br>* Scopolamine 2ug/kg over 15 minutes twice a week for 3 weeks as augmentation of ongoing antidepressant regimen<br>|
| Experimental: Ketamine plus scopolamine<br>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<br>* ketamine IV 0.25mg/kg infusions twice a week for 3 weeks as augmentation of ongoing antidepressant regimen.<br>Drug: Scopolamine<br>* Scopolamine 2ug/kg over 15 minutes twice a week for 3 weeks as augmentation of ongoing antidepressant regimen<br>|

What is the study measuring?
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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 |