Sham acupuncture and sham surgery for migraine were associated with better response rates than oral placebos, a meta-analysis found.
To determine whether different types of placebo treatments are associated with different effect sizes, researchers conducted a meta-analysis of 79 randomized clinical trials on the prophylaxis of migraine with an observation period of at least 8 weeks after randomization that compared an experimental treatment with a placebo control group.
Responders were defined as patients who had a reduction in migraine frequency of at least 50%, or if those data were not available, patients with at least a 50% reduction in the number of migraine days, with at least a 50% reduction in the number of headache days, with at least a 50% reduction in headache scores, or with significant improvement as assessed by the patients or physicians.
Results appeared online Oct. 14 at JAMA Internal Medicine.
The overall pooled proportion of responders in the active treatment groups was 0.42 (95% CI, 0.38 to 0.45) and in the placebo groups was 0.26 (95% CI, 0.22 to 0.30). Active treatment was significantly more effective than placebo treatment (RR, 1.40; 95% CI, 1.23 to 1.59). The proportion of responders with a more pronounced reduction of migraine frequency was greater for sham acupuncture (0.38; 95% CI, 0.30 to 0.47) and sham surgery (0.58, 95% CI, 0.37 to 0.77) than for oral placebos (0.22; 95% CI, 0.17 to 0.28).
“The context and meaning of a placebo treatment are more important than the placebo vehicle itself,” researchers noted. “However, the context and meaning of surgery, for example, differ considerably from those of an oral drug. Patients may develop greater expectations about treatments such as acupuncture and surgery because of the more elaborate and impressive treatment rituals. The higher level of attention and physical contact may also play a role. The most probable explanation for the apparently greater effectiveness of sham acupuncture and possibly sham surgery compared with placebo pills is thus their systematic association with contextual factors that are known to enhance placebo effects.”
Researchers noted that clinicians who treat migraineurs should be aware of placebos’ nonspecific effects and that these effects might differ between treatments.
The study may challenge the classic interpretation of randomized clinical trials that the treatment with the greatest specific effect compared with its placebo control is also the most effective one, the authors continued. An efficacy paradox occurs in which complex interventions with a small specific effect but a large placebo effect could be considered of little value while still being more effective than a simple intervention with a moderate specific effect but a small placebo effect.
An accompanying editor’s note stated, “As might be expected, the sham acupuncture and sham surgery control groups had a greater reduction of migraine frequency than the oral pharmacological placebo groups. Thus, in evaluating therapy for migraine prophylaxis, we learn from this review that like treatments should be compared, such as surgery treatment with sham surgery treatment and pill with sham pill. This important lesson extends far beyond migraine prophylaxis treatment.”