Oral Ketamine in the Treatment of Depression and Anxiety in Patients With Cancer

Study Overview
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Brief Summary
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Depression is common in patients with cancer. Current medications for depression, while effective, take several weeks to take effect. Ketamine has emerged as a drug with promise for cancer patients. In two reported cases, a single dose of ketamine induced rapid and moderately sustained symptom reduction in depression and anxiety with no adverse side effects. Benefit was seen in as little as 1 hour and sustained up to 30 days. This study is a randomized, double-blind, placebo-controlled investigation testing whether a single dose of ketamine improves depression and anxiety relative to placebo in patients with cancer.

Detailed Description
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Depression is common in patients with cancer. Current antidepressants, while effective, have an onset of action of at least several weeks. Ketamine has emerged as a drug with promise for cancer patients. It has been shown to potentiate opiate analgesic effects. Single dose parenteral and enteral administration studies in medically healthy treatment-resistant depressed patients have shown rapid relief of symptoms. A recent two patient case series reported a rapid and moderately sustained symptom reduction in depression and anxiety in palliative care patients following a single dose of oral ketamine 0.5 mg/kg, with no adverse effects. Benefit was seen as little as 1 hour after the administration and sustained up to 30 days. These case reports generate hypotheses of efficacy for ketamine in the treatment of depression and anxiety in patients with cancer. This study is a randomized, double-blind, placebo-controlled investigation of these hypotheses.

Official Title
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Oral Ketamine in the Treatment of Depression and Anxiety in Patients With Cancer

Conditions
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Cancer, Depression, Anxiety

Intervention / Treatment
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* Drug: Ketamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with cancer Outpatient status at the time of study entry 18 years of age or older Life expectancy of at least 1 month Regular access to a telephone (for safety reasons) Reliable transportation to follow-up visits Caregiver observation available for 24 hours after the dose Histologically-proven malignancy Depression score of >11 on the Hospital Anxiety and Depression Scale (HADS) Provision of informed consent Able to complete the patient questionnaires alone or with assistance Able to speak and read English May receive other psycho-active medications while on the study i.e. opiates, except as defined within the exclusion criteria May receive psychotherapy from an outside provider at the beginning and/or during the course of the study Exclusion Criteria: Obvious cognitive dysfunction or Mini Mental Status Exam score <20 Antidepressants started or dose changed within 8 weeks of the beginning of the study or during the study Benzodiazepines prescribed for psychiatric indications that have been started or dose change within 2 weeks of the beginning of study enrollment Suicidal ideation or a suicide attempt within the last year Patients with current or past psychosis not from delirium Females who are pregnant or nursing Unable to take oral medications Primary or metastatic brain malignancy Gastrointestinal tract obstruction Prior adverse reaction to or other contraindication to ketamine Substance abuse or dependence, as defined by Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria, within the last 90 days

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine<br>Single dose of ketamine (0.5 mg/kg) | Drug: Ketamine<br>* Single dose (0.5 mg/kg) of liquid ketamine 10mg/mL solution taken by mouth<br>* Other names: Ketalar;|
| Placebo Comparator: Placebo<br>Single dose of placebo | Drug: Placebo<br>* Single dose of liquid placebo solution taken by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Anxiety and Depression Scale - Anxiety Score (HADS-A) | Hospital Anxiety and Depression Scale (HADS) is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported in the literature to be >10 for anxiety and >8 for depression. | Baseline, 120 minutes | 
| Hospital Anxiety Depression Scale- Depression Score (HADS-D) | Hospital Anxiety and Depression Scale (HADS) is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) for either anxiety or depression. Cut-offs for identifying psychiatric distress has been reported in the literature to be >10 for anxiety and >8 for depression. | Baseline, 120 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, depression, anxiety, palliative care