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

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.

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