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

Phase 2

Terminated

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Single dose of placebo
Ketamine	Ketamine	Single dose of ketamine (0.5 mg/kg)

Primary Outcome Measures

Name	Time	Method
Hospital Anxiety and Depression Scale - Anxiety Score (HADS-A)	Baseline, 120 minutes	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.
Hospital Anxiety Depression Scale- Depression Score (HADS-D)	Baseline, 120 minutes	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.

Secondary Outcome Measures