The Placebo Effect in Acute Headache Management: Ketorolac, Meperidine, and Saline in the Emergency Department

Abstract

In a prospective, double-blind, randomized study, ketorolac 60 mg, meperidine 50 mg plus promethazine 25 mg, and normal saline given by intramuscular injection were compared as treatment for acute headache crises. Thirty patients (6 men and 24 women) presenting to an urban emergency department with any type of benign headache were randomized into three groups and filled out the McGill Short-Form Pain Questionnaire with a Pain Rating Index and a Visual Analogue Pain scale. They received one of the study medications and repeated the testing after 1 hour. The objective was to test the efficacy of ketorolac in this population. Separate analyses of the McGill Short-Form (Total, Sensory, Affective, and Pain Rating Index scales) and the Visual Analogue Pain scale responses showed that the three treatments produced a significant reduction in pain (P < .0001), but that pain reduction did not differ among the treatments. This profound reduction observed after administration of a placebo prevented accurate evaluation of the effects of ketorolac. The placebo response must be considered in the design of future trials using intramuscular medications in the acute intervention of headache crises. In addition, the use of a standard analgesic is necessary to demonstrate both assay sensitivity and magnitude of response to placebo.

Does therapist’s attitude affect clinical outcome of lumbar facet joint injections?

“…Symptom red [12] uction is not possible merely by consciously wanting it but can rather be achieved by subconscious belief [11] . In this context, pain and Parkinson's disease are best evaluated where the associated neurobiological effects cannot provide a conclusive explanation, but indicate a rather complex mode of action of placebo effects [13,14] . The involvement of cannabinoids and opioids is considered to be assured because placebo-associated effects can be antagonized by drugs [14] .…”

Efficacy measurement of ketorolac in reducing the severity of headache

“…The authors reported that ketorolac was superior to placebo at 0.5 and 1 hour and superior to meperidine at 2 hours (22). Interestingly, these authors had conducted the same study on acute headache crises 2 years earlier and had reported that using all three options could lead to significant pain control, but the amount did not differ among them (23). In a non-interventional non-randomized survey on pain management, intramuscular ketorolac and oral ibuprofen were compared.…”

Intravenous Ketorolac vs Intravenous Prochlorperazine for the Treatment of Migraine Headaches

“…6 Other data suggest that ketorolac is at once more expensive and less efficacious than other agents for acute migraine. 5,6 Even the manufacturer's literature shows that 17% of patients who receive ketorolac sustained headache as a side effect.…”

“…6 Other data suggest that ketorolac is at once more expensive and less efficacious than other agents for acute migraine. 5,6 Even the manufacturer's literature shows that 17% of patients who receive ketorolac sustained headache as a side effect. Thus, there is much accumulated data to suggest that ketorolac is not an optimal first-line agent for headache in the ED, thereby casting doubt on the advisability of the authors' suggestion for further studies of this agent.…”

“…Therefore, Harden et al have recommended ''the design of future headache trials using intramuscular medications must consider the placebo effect.'' 6 Unfortunately, in headache trials no data are available regarding an IV placebo effect, which one may potentially argue is less painful than an IM placebo. For this trial we considered an IV saline placebo but due to ethical considerations decided not to have placebo.…”