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

• Hospital Anxiety and Depression Scale - Depression Score (HADS-D) [ Time Frame: 120 minutes ] [ Designated as safety issue: No ]
  Depression score of the Hospital Anxiety and Depression Scale
• Hospital Anxiety and Depression Scale - Anxiety Score (HADS-A) [ Time Frame: 120 minutes ] [ Designated as safety issue: No ]
  Anxiety score of the Hospital Anxiety and Depression Scale

• HADS-D [ Time Frame: 120 minutes ] [ Designated as safety issue: No ]
  Depression score of the Hospital Anxiety and Depression Scale
• HADS-A [ Time Frame: 120 minutes ] [ Designated as safety issue: No ]
  Anxiety score of the Hospital Anxiety and Depression Scale

Depression is common in patients with advanced 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 advanced cancer.

Depression is common in patients with advanced 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 advanced cancer. This study is a randomized, double-blind, placebo-controlled investigation of these hypotheses.

• Drug: Ketamine
  Single dose of ketamine (0.5 mg/kg)
• Drug: Placebo
  Single dose of placebo

• Experimental: Ketamine
  Single dose of ketamine (0.5 mg/kg)
  Intervention: Drug: Ketamine
• Placebo Comparator: Placebo
  Single dose of placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Patients with advanced-stage 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 solid tumor malignancy
• Depression score of >11 on the 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