Intra-nasal vs. Intra-venous Ketamine Administration

Study Overview
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Brief Summary
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The current study wishes to contribute to the applicability of the use of ketamine in a clinical setting by focusing on the efficacy of intra-nasal administration compared with the IV route.

Official Title
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Intra-nasal vs. Intra-venous Ketamine Administration as an add-on to Antidepressant Therapy

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Placebo
* Drug: Ketamine (1st phase)
* Drug: Ketamine (2st phase)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 Diagnosis of MDD (Major Depressive Disorder), made or affirmed by a senior psychiatrist in Shalvata MADRS score > 20 Treated with conventional anti-depressant, administered within a formal psychiatric clinic or by a certified psychiatrist. Exclusion Criteria: Active or past psychotic disorder, including a history of psychotic affective state Mental Retardation or Autistic Spectrum Disorder Prominent personality disorder Cardiac or neurologic active medical condition, including past CVA/TIA (Cardiovascular Accident/Transient Ischemic Attack) or any other unstable medical condition. Chronic nasal congestion Active or recent drug or alcohol abuse Substantial suicidality in a patient requiring admission but refuses to do so, and signs an against medical advice release form as part of clinical evaluation, and does not answer the terms for involuntary admission.

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 |
| --- | --- |
| Active Comparator: Active IV<br>Will receive IV Ketamine, along with IN placebo. | Drug: Placebo<br>* Saline 0.9%, Administration of 0.2mg/kg (IV Push) or 50mg (IN, 5 doses, alternating nostrils)<br>* Other names: Saline 0.9%;Drug: Ketamine (1st phase)<br>* Administration of 0.2mg/kg (IV Push) or 50mg (IN, 5 doses, alternating nostrils)<br>* Other names: Ketalar;Drug: Ketamine (2st phase)<br>* Patients failing to achieve response (<50% MADRS score) in the parallal phase, will be offered additional 4 session (twice a week, 2 weeks) of 0.5 mg/kg ketamine over 40 minutes.<br>* Other names: Ketalar;|
| Active Comparator: Active IN<br>Will receive IN Ketamine, along with IV placebo. | Drug: Placebo<br>* Saline 0.9%, Administration of 0.2mg/kg (IV Push) or 50mg (IN, 5 doses, alternating nostrils)<br>* Other names: Saline 0.9%;Drug: Ketamine (1st phase)<br>* Administration of 0.2mg/kg (IV Push) or 50mg (IN, 5 doses, alternating nostrils)<br>* Other names: Ketalar;Drug: Ketamine (2st phase)<br>* Patients failing to achieve response (<50% MADRS score) in the parallal phase, will be offered additional 4 session (twice a week, 2 weeks) of 0.5 mg/kg ketamine over 40 minutes.<br>* Other names: Ketalar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MADRS (Montgomery-Åsberg Depression Rating Scale) score improvement from baseline |  | 15 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of subjects achieving remission |  | 15 weeks | 
| Ratio of subjects achieving Response |  | 15 weeks | 
| Durability of anti-depressant effect according to MADRS Score | The rate of effect decline, as measured by MADRS Questionnaire | 15 weeks | 
| Tolerability of Route, based on side effects questionnaire | Adverse side effects reported by subjects, as reported in side effects questionnaire | 3 weeks |