The objective of this thesis was to investigate the safety and efficacy of single and repeated administration of ketamine as a fast acting antidepressant in patients with terminal cancer. Associated with this objective was a comprehensive review of the pathophysiology of major depressive disorder, existing treatments for major depressive disorder, and a review and meta- analysis of treatments for depression in patients with cancer. The use of ketamine in treatment-resistant depression was also reviewed, along with a meta-analysis of mood responses in placebo-controlled studies, and data from case reports and case series.
The review and meta-analysis of antidepressant treatments for depression in cancer patients yielded only two small placebo-controlled randomized trials, both for mianserin. No psychotherapy trials were found that met inclusion criteria for this analysis. The two mianserin trials showed a benefit in improving mood ratings compared with placebo. The very limited amount of data on treatment of depression in this population is surprising, and further research is needed to improve knowledge in this area.
The review and meta-analysis of mood responses to ketamine in three placebo-controlled randomized crossover studies demonstrated a robust improvement in mood ratings by four hours, that was sustained up to 72 hours. Uncontrolled data from case series and case reports showed similar profile to data reported from the placebo-controlled studies.
The study investigates the effect of ketamine on mood ratings in depressed patients with cancer had three stages; (1) to assess whether a single 1 mg/kg IM dose improved mood; (2) to assess the effect of repeated 1 mg/kg IM dosing on mood; and (3) to assess the mood responses to IM doses of 0.1, 0.5 or 1.0 mg/kg IM. This thesis reports the case of a single patient who participated in Stages 1 and 2. The results in the case presented in this thesis were positive, with remission of symptoms with single dose and repeated treatment, and maintenance of remission with weekly injections of ketamine 1 mg/kg.
This thesis supports the possible use of ketamine as a fast acting antidepressant in terminal cancer patients with Major Depressive Disorder. In a population with short life expectancy, the existence of a treatment for depressive episodes with rapid onset of action would be essential, and ketamine might be the option of choice.
