More recently discussed as a drug that induces a mood-state change devolving to a longer-term augmentive antidepressant effect in persons with erstwhile treatment-resistant depression, ketamine has analgesic effects for acute and chronic pain that have been documented plenteously over nearly two decades in both children and adults. A recent study by Iranian clinical researchers (A. Forouzan and colleages, Review of Recent Clinical Trials, published on the Web on July 5, 2019) offers a recent example in the form of a comparison of ketamine and morphine in persons with unequivocal, severe acute pain.
The authors randomly allocated 135 patients who presented to their emergency department with renal colic to double-blind treatment either with morphine (0.1 mg/kg i.v.) or ketamine (0.3 mg/kg i.v.). Pretreatment pain ratings were the same in both groups (9.2/10).
Rating their patients 10, 20, 30, and 60 minutes after treatment, the authors observed similar pain reductions in both groups, with ketamine seeming to have a (statistically insignificantly) more rapid onset. Moreover, during the patients’ subsequent hospital treatment, ketamine-treated patients required fewer prn doses of fentanyl. Three ketamine-treated patients experienced treatment-emergent nausea or vomiting.
Like many observers before them who have conducted trials of ketamine in persons with less severe pain or chronic pain of diverse etiology, the authors conclude that ketamine may have potent analgesic properties. They offer no speculation about a potential mechanism therefor, and they do not mention well-documented effects of ketamine on mu opioid receptors or clinical opioid-like manifestations of ketamine. (Obiter: Nor do they mention ketamine’s mood-elevating properties, or those of some opioid compounds (which, when eventually recruited as comparators of ketamine in trials of treatment-resistant depression, may show similar mood-elevating properties with similar dosing schedules. Obiter II: Over the last seventeen years, several randomized, controlled trials have revealed statistically and clinically significant analgesic effects of ketamine in persons with post-surgical pain, pain associated with burns, extremity fractures (in children), amputation, sickle cell crisis, dental surgery (in children), cancer, and vascular headache. No withdrawal phenomena have been observed with short-term dosing, and adverse effects of ketamine overall have been less frequent and less severe than those of opioids. Yet, no systematic (intentional) trials have illuminated whether longer-term dosing with ketamine may eventuate in opioid-like withdrawal phenomena (as may have occurred in FDA’s discontinuation trial of ketamine pursuant to its application for approval for treatment-resistant depression.)