The finding: After six weeks, subjects receiving 50mg ketamine by mouth TID demonstrated superior response to treatment and greater depression remission rates than subjects receiving 50mg diclofenac by mouth TID. Minimal adverse effects were noted; oral ketamine was well tolerated with no evidence of transient psychotomimetic effects.

Strength and weaknesses: The major strength is the rigorous study design – a double-blind, controlled, and randomized trial. As the authors noted, this study only examined 20 subjects for six weeks. Despite this being a short follow-up time, the six-week interval proved long enough to demonstrate a statistically significant difference in HRDS scores, which was not evident after only three weeks. HRDS is better able to demonstrate improvement and remission than HADS, which serves more as a screening tool.

Relevance: Ketamine has been repeatedly identified as a potential agent for rapid intervention and improvement in depression symptoms. This is the first RCT to demonstrate comparable efficacy and safety of oral ketamine and diclofenac.

The finding: Using a systematic review of the literature and meta-analysis, the authors compiled a sample of 641 patients with depression and 676 healthy controls. Various pain modalities were studied, measuring threshold, intensity, and pain tolerance. The authors concluded that depression might be associated with a reduced sensitivity to low-intensity pain stimuli. They also noted that depressed subjects demonstrated increased response to ischemic stimuli, but equivalent or reduced response to other pain modalities.

Strength and weaknesses: This is the largest meta-analysis of experimental pain induction studies of people with depression. The main weaknesses are the heterogeneous test modalities and measures. Furthermore, the data may be affected by the limited treatment of depression as 16 of the 32 studies examined unmedicated subjects, while 10 of the remaining 16 were either mixed treatments or not stated.

Relevance: The findings of this meta-analysis support the relationship between mood and pain perception; however, this relationship is complex and requires further examination.